FULL DETAILS (Read-only)

CTRI Number  CTRI/2020/03/024402 [Registered on: 31/03/2020] Trial Registered Prospectively
Last Modified On: 31/03/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug
Preventive 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Hydroxy Chloroquine, in open labelled, Randomised intervention for prevention of new infection and adverse outcomes following COVID-19 infection -A Tertiary Hospital based study 
Scientific Title of Study   Hydroxy Chloroquine, in open labelled, Randomised intervention for prevention of new infection and adverse outcomes following COVID-19 infection- A Tertiary Hospital based study 
Secondary IDs if Any  
Secondary ID  Registry 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Remesh Bhasi 
Address  Aster Malabar Institute of Medical Sciences (MIMS) P O Govindapuram Kozhikode Kerala India 673016

Kozhikode
KERALA
673016
India 
Phone  9447010634  
Fax  4952741329  
Email  remesh.bhasi@asterhospital.com  
 
Details Contact Person
Scientific Query

Modification(s)  
Name  Dr Remesh Bhasi 
Address  Aster Malabar Institute of Medical Sciences (MIMS) P O Govindapuram Kozhikode Kerala India 673016

Kozhikode
KERALA
673016
India 
Phone  9447010634  
Fax  4952741329  
Email  remesh.bhasi@asterhospital.com  
 
Details Contact Person
Public Query

Modification(s)  
Name  Dr Remesh Bhasi 
Address  Aster Malabar Institute of Medical Sciences (MIMS) P O Govindapuram Kozhikode Kerala India 673016

Kozhikode
KERALA
673016
India 
Phone  9447010634  
Fax  4952741329  
Email  remesh.bhasi@asterhospital.com  
 
Source of Monetary or Material Support  
Aster Malabar Institute of Medical Sciences 
 
Primary Sponsor
Modification(s)  
Name  Dr Remesh Bhasi 
Address  HOD Department of Rheumatology Aster MIMS P O Govindapuram Kozhikode Kerala India 673016 
Type of Sponsor  Other [individual] 
 
Details of Secondary Sponsor  
Name  Address 
Aster MIMS  P O Govindapuram Kozhikode Kerala India 673016 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 1  
Contact Person  Name of Site  Site Address  Phone/Fax/Email 
Dr Remesh Bhasi  Aster Malabar Institute of Medical Sciences  P O Govindapuram Kozhikode Kerala India 673016
Kozhikode
 
9447010634
4952741329
remesh.bhasi@asterhospital.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Malabar Institute of Medical Sciences Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  COVID- 19 (Prevention of infection)  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Comparator Agent  Hydro Chloroquine(HCQ)-ICMR regimen  Group 2 : 400 mg bd for one day followed by 400 mg weekly for 7 weeks to be taken with meals (or until the epidemic stops) (ICMR Regimen) Both groups will be advised to follow strict measures of self hygiene, social distancing and other routine protocols issued by IMA and Government bodies to prevent transmission.  
Intervention  Hydroxychloroquine   300 mg daily x 7 days followed by 300 mg weekly x 7 weeks 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  1. Moderate to high risk of exposure to infected patients during the study period.
2. Healthy at the time of enrolment without any symptoms suggestive of any viral infection. 
 
ExclusionCriteria 
Details  1. History of known allergy to Hydro ChloroQuine(HCQ) or Chloroquine
2. Known contraindications for HCQ or Chloroquine including Retinopathy, known Cardiac disease like Dysarrythmias, and G6PD deficiency.
3. Pregnancy and Lactation
4. History of recent (within one month) International travel.
5. Features of any ongoing infection including COVID-19 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Infected Non infected  Time to clinical improvement 
 
Secondary Outcome  
Outcome  TimePoints 
Mortality, percentage of patients who had clinical improvement, oxygen support days, Mechanical ventilation, ICU stay days, total hospital stay, clinical score, MODs plus or minus  28 days mortality
7 day and 14 day clinical score and all others at the time of discharge  
 
Target Sample Size
Modification(s)  
Total Sample Size="500"
Sample Size from India="500" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)
Modification(s)  
08/04/2020 
Date of First Enrollment (Global)  No Date Specified 
Estimated Duration of Trial   Years="0"
Months="3"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details    
Brief Summary
Modification(s)  
CORONA study is a randomised open label study which compares two dosing regimens of hydroxychloroquine sulphate for prophylaxis against coven 19.
The expected enrolment is 500 healthy volunteers working at a tertiary care centre in Kerala.
 

CTRI Number  CTRI/2020/05/025013 [Registered on: 05/05/2020] Trial Registered Prospectively
Last Modified On: 04/05/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study
Modification(s)  
Vaccine 
Study Design  Non-randomized, Active Controlled Trial 
Public Title of Study   Evaluation of BCG as potential therapy for COVID-19 
Scientific Title of Study
Modification(s)  
Phase 2 Clinical Trial for the Evaluation of BCG as potential therapy for CoVID-I9 
Secondary IDs if Any
Modification(s)  
Secondary ID  Registry 
BIO/CT/20/000049  DCGI 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Rajesh Deshmukh 
Address  Haffkine Institute for Training Research and Testing Acharya Donde Marg Parel, Mumbai 400012
Haffkine Institute for Training Research and Testing Acharya Donde Marg Parel, Mumbai 400012
Mumbai
MAHARASHTRA
400012
India 
Phone  02224160947  
Fax  02224161787  
Email  director@haffkineinstitute.org  
 
Details Contact Person
Scientific Query

Modification(s)  
Name  Dr Usha Padmanabhan  
Address  Biochemistry Department, Haffkine Institute for Training Research and Testing Acharya Donde Marg Parel, Mumbai 400012 Tel 022-24160947 ext 220, 232 Fax 022-24161787
Same as address 1
Mumbai
MAHARASHTRA
400012
India 
Phone  02224160947  
Fax  02224161787  
Email  u.padmanabhan@haffkineinstitute.org  
 
Details Contact Person
Public Query

Modification(s)  
Name  Dr Sanjay Mukherjee 
Address  9th floor, Mantralay, GT Hospital Campus, Fort, Mumbai
9th floor, Mantralay, GT Hospital Campus, Fort, Mumbai
Mumbai
MAHARASHTRA
400001
India 
Phone  022-22622179  
Fax    
Email  psec.mededu@maharashtra.gov.in  
 
Source of Monetary or Material Support  
Medical Education and Drugs Department 9th floor, Mantralay, GT Hospital Campus, Fort, Mumbai 400001 
 
Primary Sponsor  
Name  Medical Education and Drugs Department 
Address  9th floor, Mantralay, GT Hospital Campus, Fort, Mumbai 400001 
Type of Sponsor  Government funding agency 
 
Details of Secondary Sponsor  
Name  Address 
Haffkine Institute for Training Research Testing  Acharya Donde Marg, Parel, Mumbai 400 012 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 1  
Contact Person  Name of Site  Site Address  Phone/Fax/Email 
Dr Sonali Salvi  Sassoon General Hospital  Jai Prakash Narayan Road, Near Pune Railway Station, Pune - 411001
Pune
 
02026126010
02026126868
sonalionly@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
BJ Medical College and SGH  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  Coronavirus as the cause of diseases classified elsewhere 
Patients  Respiratory conditions due to unspecified external agent 
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  BCG plus STANDARD of CARE as suggested by DCGI  DOSE 0.1 ml ROUTE OF ADMINISTRATION Intradermal FREQUENCY Only once during the entire trial DURATION 1-2 min time required to inject subject. It is not continuous therapy.  
Comparator Agent  SALINE plus STANDARD of CARE as suggested by DCGI  DOSE 0.1 ml ROUTE OF ADMINISTRATION Intradermal FREQUENCY Only once during the entire trial DURATION 1-2 min time required to inject subject. It is not continuous therapy. 
 
Inclusion Criteria
Modification(s)  
Age From  20.00 Year(s)
Age To  40.00 Year(s)
Gender  Both 
Details  Hospitalized subjects either male or female with confirmed COVID-19 will be included in this as per following criteria:
1. Age 20 - 50 years
2. Symptomatic subjects with fever (using self-reported questionnaire) plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus
3. Positive SARS-Cov-2 test in nasopharyngeal sample at admission (using RT-PCR as prescribed by WHO, ICMR and NCDC)  
 
ExclusionCriteria 
Details  Subjects outside the age group
Subjects who test negative for nCOV-19 by RT-PCR as per criteria laid down by ICMR.
Subjects with
1. Any co-morbidities such as renal distress, cardiac malfunction etc. at time of admission
2. Any disorder in which natural immune response is altered,
3. Systemic lupus
4. Hypogamma-globulinemia,
5. Congenital immunodeficiency,
6. Sarcoidosis,
7. Leukaemia,
8. Generalised malignancy,
9. HIV infections or as also those on immunosuppressive therapy, corticosteroids, radiotherapy.
10. Inchronic eczema or other dermatological disease
11. Pregnant women, lactating (breast-feeding) women 
 
Method of Generating Random Sequence   Other 
Method of Concealment   On-site computer system 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
Primary Outcome Measures:
1.Total duration of Hospitalization with COVID-19 symptoms such as febrile respiratory distress [Time Frame: from admission until discharge]
2.Decrease in Viral Titer [Time Frame: Measured on day of enrolment, on day 7 and 15 after intervention]
3.Duration of COVID-19 symptoms [Time Frame: At time of admission, following enrollment until discharge] 
Primary Outcome Measures:
1.Total duration of Hospitalization with COVID-19 symptoms such as febrile respiratory distress [Time Frame: from admission until discharge]
2.Decrease in Viral Titer [Time Frame: Measured on day of enrolment, on day 7 and 15 after intervention]
3.Duration of COVID-19 symptoms [Time Frame: At time of admission, following enrollment until discharge] 
 
Secondary Outcome  
Outcome  TimePoints 
1. Change in IgG and IgM induced by nCoV-19 in serum [Time Day 0 and days 7 and 15 after BCG intervention]
2. Change in total IgG and IgM levels in serum [Time Day 0 and days 7 and 15 after BCG intervention]
3. Change in Th1 and Th2 cytokines as assessed by RT-PCR using RNA extracted from hematocrit [Time Day 0 and days 7 and 15 after BCG intervention] 
1. Change in IgG and IgM induced by nCoV-19 in serum [Time Day 0 and days 7 and 15 after BCG intervention]
2. Change in total IgG and IgM levels in serum [Time Day 0 and days 7 and 15 after BCG intervention]
3. Change in Th1 and Th2 cytokines as assessed by RT-PCR using RNA extracted from hematocrit [Time Day 0 and days 7 and 15 after BCG intervention] 
1.Local and systemic adverse events to BCG vaccination. [Time Enrolment to 3 months]
2.No. of ICU admissions [Time Enrolment to 3 months]
3.Duration of ICU admission [Time Enrolment to 3 months]
4.Number of participants needing mechanical ventilation [Time Enrolment to 3 months]
5.Duration of Mechanical ventilation [Time Enrolment to 3 months]
6.Mortality [Time From enrolment]
7.Time for resolution of COVID-19 disease [Time From enrollment]
8.Hospitalization cost [Time From enrollment] 
1.Local and systemic adverse events to BCG vaccination. [Time Enrolment to 3 months]
2.No. of ICU admissions [Time Enrolment to 3 months]
3.Duration of ICU admission [Time Enrolment to 3 months]
4.Number of participants needing mechanical ventilation [Time Enrolment to 3 months]
5.Duration of Mechanical ventilation [Time Enrolment to 3 months]
6.Mortality [Time From enrolment]
7.Time for resolution of COVID-19 disease [Time From enrollment]
8.Hospitalization cost [Time From enrollment] 
 
Target Sample Size
Modification(s)  
Total Sample Size="60"
Sample Size from India="60" 
Phase of Trial
Modification(s)  
Phase 2 
Date of First Enrollment (India)
Modification(s)  
06/05/2020 
Date of First Enrollment (Global)  No Date Specified 
Estimated Duration of Trial   Years="0"
Months="3"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   none 
Brief Summary  

Evaluation of BCG as potential therapy for COVID-19

Summary

Background and Introduction

The novel coronavirus nCoV-19 (or SARS-CoV-2 or 2019-nCoV), responsible for the global pandemic COVID-19 was isolated from human airway epithelial cells from patients from Wuhan, China in December 2019 (Wang et al, 2020; Zhu et al, 2020).  Seven coronaviruses (CoVs) have been described so far infecting humans of which the SARS-CoV (Kuiken et al, 2003), MERS-CoV and nCoV-19 are serious threats to humans. No therapies or vaccines have been approved for SARS or MERS thus far, demonstrating the need to develop effective therapies or vaccines.

 

BacilleCalmette-Guérin, BCG is a vaccine against tuberculosis that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis. The bacilli have retained enough strong antigenicity to become an 80% effective vaccine for the prevention of human tuberculosis. Overall, BCG vaccine reduces the risk of pulmonary and extra-pulmonary tuberculosis (TB) by approximately 50%, but it has 64% efficacy against TB meningitis and 78% against disseminated TB disease.  India and Pakistan introduced BCG mass immunization in 1948, the first countries outside Europe to do so. BCG as a vaccine is safe to be used in children within a week of their birth and is in the Universal immunization programs of many countries in South East Asia and Africa.

BCG vaccine also provides some protection against leprosyand non-tuberculous mycobacterial infections. In addition, it has been used in the treatment of superficial carcinoma of the bladder.

It has been shown to reduce severe respiratory distress in children from Africa and conferred beneficial immunity and favorable outcomes to malarial infections. Revaccination with BCG has been tried in some populations (Japanese adults). However the longevity of immune protection due to re-vaccination has not yet been confirmed.

 

BCG Strains

Currently, five main strains account for more than 90% of the vaccines in use worldwide with each strain possessing different characteristics. The strains include the Pasteur 1173 P2, the Danish 1331, the Glaxo 1077 (derived from the Danish strain), the Tokyo 172-1, the Russian BCG-I,and the Moreau RDJ strains (Hayashi et al, 2009).

Each strain of BCG has a different reactogenicity profile - The Pasteur 1173 P2 and Danish 1331 strains are known to induce more adverse reactions than the Glaxo 1077, Tokyo 172-1, or Moreau RDJ strains (Hayashi et al., 2009).  The strain is one of the important factors that has been implicated in incidence of adverse events following BCG vaccination (Milstienet al,1990, Lotte et al.,1984). The BCG to be used in this protocol is Tubervac (Serum Institute of India) is derived from the Russian strain, also known as Moscow strain.

Safety of use of BCG

WHO estimates that 80% of the world is covered by BCG i.e. atleast 100 million children with one year of birth are given the vaccine worldwide, a statistic which speaks for the safety of the vaccine.

One of the most common side effects of BCG vaccinations are local complications (injection site reactions and suppurative or non-suppurative lymphadenitis). Management of the same varies between clinicians, and the optimal approach remains uncertain. In addition, the following adverse events have been noted in dispersed populations.

Skin lesions distinct from the vaccination site. Tuberculosis infection can cause a number of cutaneous lesions (such as TB chancre, lupus vulgaris, scrofuloderma, papulonecrotic tuberculids etc). There are case reports of cutaneous lesions, distinct from the site of vaccination, thought to have occurred after BCG vaccination (Bellet et al., 2005). It is important to note that multiple cutaneous lesions may signal disseminated BCG disease usually in an immunocompromised host. There are case reports of lupus vulgaris, scrofuloderma following BCG vaccination.

Lymphadenitis. When severe, this includes nodes which become adherent to overlying skin with or without suppuration. Suppuration has been defined as "presence of fluctuation on palpation or pus on aspiration, the presence of a sinus, or large lymph node adherent to the skin with a caseous lesions on excision" (Lotte et al., 1984). If BCG is administered in the recommended site (deltoid) the ipsilateral axillary nodes are most likely to be affected but supra-clavicular or cervical nodes may also be involved (Hengster et al., 1992). The onset of suppuration may be variable with cases presenting from one week to 11 months following vaccination (de Souza et al., 1983). Lymphadenitis presenting within 2 months of vaccination and larger nodes (+ 1cm) may be less likely to resolve spontaneously (Caglayan et al., 1991). Suppurative lymphadenitis is now rare, especially when BCG inoculations are performed by well-trained staff, with a standardized freeze-dried vaccine and a clearly stated individual dose depending on the age of the vaccinated subjects.

Osteitis and Osteomyelitis. This is a rare and severe complication of BCG vaccination which has primarily been reported in Scandinavia and Eastern Europe and typically associated with changes in BCG vaccine strain. There was a report of an increase in osteitis to 35 per million in Czechoslovakia after a shift from the Prague to Russian strain BCG (Lotte, et al., 1988). Both Finland and Sweden reported increases in osteitis after 1971 when they shifted to a Gothenburg strain produced in Denmark. Sweden reported rates as high as 1 in 3,000 vaccine recipients, which declined rapidly when the national programme shifted to a Danish (Copenhagen, 1331) vaccine strain (Lotte et al., 1988). More recently reports of osteitis have become infrequent.

Disseminated BCG disease or systemic BCG-itis. This recognized but rare consequence of BCG vaccination traditionally has been seen in individuals with severe cellular immune deficiencies. The risk (fatal and non-fatal) is thought to be between 1.56 / million and 4.29 cases / million doses (Lotte et al., 1988). This is based on pre-HIV data. However, the exact incidence is debated because few centers are able to differentiate Mycobacterium Bovis BCG from other forms of Mycobacterium in patients presenting with disseminated disease. In a recent retrospective case series review of Mycobacteriunm tuberculosis complex 5% of cases were found to have the M. Bovis BCG strain (Hesseling et al., 2006). Additional data from studies in South Africa confirm the significantly high risk of disseminated BCG (dBCG) disease in HIV-positive infants, with rates approaching 1% (Hesseling et al., 2009). In one series of 60 cases of BCG-itis the case fatality rate was approximately 50% although other smaller studies have documented a higher mortality rate (Lotte et al., 1988, Talbot et al., 1997). As expected the cellular primary immunodeficiency predisposes to the condition. This includes severe combined immunodeficiency, chronic granulomatous disease, Di George syndrome and homozygous complete or partial interferon gamma receptor deficiency (Jouanguy et al., 1996; Jouanguy et al., 1997; Casanova et al., 1995).

Early recognition and diagnosis is critical to management. In patients with primary immunodeficiency disorders the disease may be fatal without reconstitution of immunity through stem cell transplant.

Immune reconstitution inflammatory syndrome (IRIS). This has recently been identified as a BCG vaccine-related adverse event in immunocompromised individuals due to HIV started on antiretroviral therapy (ART) (DeSimone et al., 2000). It usually presents within 3 months of immune restoration and manifests as local abscesses or regional lymphadenitis usually without dissemination. No fatal cases have yet been documented.  A number of rare events have been reported as case reports or series. These include sarcoidosis, ocular lesions (conjunctivitis, choroiditis, optic neuritis), and erythema nodosum. Tuberculous meningitis (due to the BCG) has been described but is exceptionally rare (Tardieu et al., 1988)

Therefore, as noted above, most of adverse effects of the use of BCG is due to two factors (1) Strain used or change in strain (which has happened in some countries, when they switch suppliers) and (2) Immune status of the individual / population and widespread use of the BCG has demonstrated some advantages, such as excellent immune adjuvant activity, long-persisting effects, safety, and low cost.

Rationale to use BCG as a therapy for COVID-19

Miller et al, 2020 show a negative correlation between BCG immunization status of a country and mortalities due to COVID-19. In particular, Miller et al., 2020 have presented epidemiological data,that suggests that BCG could be effective against nCoV-19 or SARS-CoV-2.  The data (yet to be peer reviewed) found that countries that do not have a BCG immunization policy have more COVID-19 deaths and cases. These countries include the US, the Netherlands and Italy. Countries like Iran which started giving the vaccine late in 1984, had high mortality, suggesting that BCG protected the vaccinated elderly population, whereas countries like Japan have reported lesser cases and mortalities. 

In addition, Two international trials are on for assessing BCG as a prophylactic agent in healthcare workers in Australia and Netherlands against COVID-19.

BCG is known to induce a potent Th1-type response (in particular to increase IFN-gamm) and promote the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. In the latter case, it is likely, however, that BCG stimulates general immune response. This results in faster response to infections that could reduce severity of disease and lead to faster recovery.

This protocol aims to evaluate the effects of BCG used as an interventional therapy on nCoV-19 positive subjects and establish a direct link between BCG inoculation and favorable COVID-19 outcome.

 

CTRI Number  CTRI/2020/04/024773 [Registered on: 21/04/2020] Trial Registered Prospectively
Last Modified On: 27/08/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug
Biological 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study
Modification(s)  
A clinical trial to study the effects of additional treatments for patients hospitalized and receiving treatment due to COVID -19. 
Scientific Title of Study   An international randomised trial of additional treatments for COVID-19 in hospitalised patients who are all receiving the local standard of care 
Secondary IDs if Any
Modification(s)  
Secondary ID  Registry 
ISRCTN83971151  ISRCTN 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  DrSheela Virendra Godbole 
Address  ICMR-National AIDS Research Institute, Pune G 73 BLOCK MIDC BHOSARI PUNE

Pune
MAHARASHTRA
411026
India 
Phone  09422087972  
Fax  27121071  
Email  sgodbole@nariindia.org  
 
Details Contact Person
Scientific Query
 
Name  DrSheela Virendra Godbole 
Address  ICMR-National AIDS Research Institute, Pune G 73 BLOCK MIDC BHOSARI PUNE

Pune
MAHARASHTRA
411026
India 
Phone  09422087972  
Fax  27121071  
Email  sgodbole@nariindia.org  
 
Details Contact Person
Public Query
 
Name  DrSheela Virendra Godbole 
Address  ICMR-National AIDS Research Institute, Pune G 73 BLOCK MIDC BHOSARI PUNE

Pune
MAHARASHTRA
411026
India 
Phone  09422087972  
Fax  27121071  
Email  sgodbole@nariindia.org  
 
Source of Monetary or Material Support  
World Health Organization and Indian Council of Medical Research 
 
Primary Sponsor  
Name  World Health Organization 
Address  Avenue Appia 20 Geneva 1211 Switzerland  
Type of Sponsor  Other [International Research Organization] 
 
Details of Secondary Sponsor  
Name  Address 
Indian Council of Medical Research  V. Ramalingaswami Bhawan, P.O. Box No. 4911 Ansari Nagar, New Delhi - 110029, India Ph: 91-11-26588895 / 91-11-26588980, 91-11-26589794 / 91-11-26589336, 91-11-26588707 Fax: 91-11-26588662 Email:icmrhqds[at]sansad[dot]nic[dot]in 
 
Countries of Recruitment     Argentina
Brazil
Canada
Germany
India
Indonesia
Iran (Islamic Republic of)
Norway
Peru
Qatar
South Africa
Spain
Switzerland
Thailand  
Sites of Study
Modification(s)  
No of Sites = 29  
Contact Person  Name of Site  Site Address  Phone/Fax/Email 
Dr Sudhir Bhandari  Sawai Man Singh Medical College Medical College & attached Hospitals, Jaipur  Jawahar Lal Nehru Marg, Jaipur, Rajasthan 302004
Jaipur
 
9829078844

drs_bhandari@yahoo.com 
Dr Rajnish Joshi  AIIMS,Bhopal  Saket nagar, Bhopal, Madhya Pradesh, 462024
Bhopal
 
9425303401

rajnish.genmed@aiimsbhopal.edu.in 
Dr Prasan Kumar Panda  All India Institute of Medical Sciences (AIIMS), Rishikesh  Virbhadra road, Shivaji Nagar Near Barrage, Sturida Colony Rishikesh, Uttarakhand India
Dehradun
 
9868999488

prasan.med@aiimsrishikesh.edu.in 
DrNishant Kumar Chauhan  All India Institute of Medical Sciences, Jodhpur  "All India Institute Of Medical Sciences (AIIMS),Basni Industrial Area Phase-2, Jodhpur-342005, Rajasthan. "
Jodhpur
 
8003996884

nishant97@gmail.com 
Dr Manish Soneja   All India Institute of Medical Sciences,N. Delhi  Ansari Nagar N. Delhi 110029 AIIMS, New Delhi
New Delhi
 
9013074717

manishsoneja@gmail.com 
DrBharath Kumar Tirupakuzhi Vijayaraghavan  Apollo Hospitals Enterprises Limited  No-21 Greams Lane off Greams road Chennai Chennai Tamil Nadu - 600006 India
Chennai
 
9591100655

bharath@icuconsultants.com 
Dr D Suresh Kumar   Apollo Specialty Hospitals, Vanagaram, Chennai  Apollo Specialty Hospitals, Vanagaram, Chennai
Chennai
 
9444186807

dsk_1973@yahoo.com 
Dr Vikas Marwah  Army Institute of Cardio- thoracic Sciences (under AFMC)  Wanowrie, Pune - 411040
Pune
 
9560503335

docvikasmarwah@gmail.com 
Dr Jignesh Shah  Bharati Vidyapeeth Deemed University Medical College  Room No 4, Pediatric OPD, Bharathi Hospital and Research Centre,Dhankawadi Katraj Pune
Pune
 
9028246946

drshahjignesh78@gmail.com 
Dr Kamlesh Upadhyay  BJ Medical College and Civil Hospital AhmedabadGujrat  B.J. Medical College,New Civil Hospital Asarwa,Ahmedabad-380016,Gujarat,India
Ahmadabad
 
9825362253

drkjupadhyay@hotmail.com 
Dr Rohida Borse  BJ Medical College and Sasson General Hospital   Near Pune Railway Station
Pune
 
9763201215

rohidas_borse@yahoo.co.in 
Dr Krishna Gopal Singh   Chirayu Medical College and Hospital  Chirayu Medical College & Hospital, Department of Pulmonary Medicine, Chirayu Medical College &Hospial, Bhainsakhedi, Near Biragarh, Bhopal-Indore highway, Bhopal, (M.P) - 462030
Bhopal
 
7566317444

dr.krishna2505@gmail.com 
Dr O C Abraham  Christian Medical College, Vellore  Vellore, Tamil Nadu PIN 632002
Vellore
 
9994068771

ocabraham@cmcvellore.ac.in 
Dr M Rajarao  Gandhi Medical College and Hospital  Musheerabad, Secunderabad, Hyderabad, Telangana - 500003 India
Hyderabad
 
9849010915

dr.mrrao@gmail.com 
Dr Chirag Rathod  GMERS Medical College & Hospital - Gotri  GMERS Medical College, Old TB Hospital Campus, Gotri, Vadodara, Gujarat - 390021
Vadodara
 
9173765727

chirag_rthd@rediffmail.com 
Dr R Narayana Babu  Goverment Medical College, Omandurar Goverment Estate, Chennai  Goverment Medical College, Omandurar Goverment Estate, Chenna
Chennai
 
9840426324

rameshkumar4v@yahoo.co.in 
Dr Dipti Chand  Government Medical College and Hospital, Nagpural  Medical College Square road, Nagpur - 440003
Nagpur
 
9823257601

dachand.ngp@gmail.com 
Dr Krishnakant Bhatt  Government Medical College and New Civil Hospital, Surat  Outside Majura gate, Surat, Gujrat – 395 001
Surat
 
9825190476

knbsurat@gmail.com 
Dr Sheela Virendra Godbole  Lead Institute for this trial is ICMR-National AIDS Research Instiute   ICMR-National AIDS Research Institute, G 73 Block MIDC, Bhosari ,Pune 411026
Pune
 
9422087972

sgodbole@nariindia.org 
Dr R Jayanthi  Madras Medical College & Rajiv Gandhi Government General Hospital  Poonamallee High Road, Park Town, Chennai, Tamil Nadu -600003
Chennai
 
9840025339

gghdean@gmail.com 
Dr Arun Dewan  Max Smart Super Speciality Hospital  Max Smart Super Speciality Hospital (A unit of Gujarmal Modi hospital and Research Centre of Medical Sciences) 1, 2, Press Enclave Marg, Saket Institutional Area, Saket, New Delhi, Delhi 110017
New Delhi
 
9810091290

Arun.Dewan@maxhealthcare.com 
Dr Zarir F Udwadia  P D Hinduja Hospital and Medical Research Centre  Unit of National Health & Education Society Veer Savarkar Marg, Mahim (West), Mumbai - 400016
Mumbai
 
9820225309

zfudwadia@gmail.com 
Dr Aarti Trivedi  P D U Govt Medical College, Rajkot  Jamnagar Road, Rajkot
Rajkot
 
9824206541

aaratitrivedi@gmail.com 
Dr Pravin Soni  Pimpri Chinchwad Municipal Corporation Postgraduate Institute & Yashwantrao Chavan Memorial Hospital  YCM Hospital Rd, Sant Tukaram Nagar, Pimpri Colony, Pune, Maharashtra 411018
Pune
 
9822057511

drpravinsoni18@gmail.com 
Dr Anushka Kaustubh Waikar  Rajarshee Chhatrapati Shahu Maharaj Government Medical College,Kolhapur   Rajarshee Chhatrapati Shahu Maharaj Government Medical College and hospital, Bhausinghji Road, Dasara Chowk, Kolhapur -416002
Kolhapur
 
7028920050

waikaranushka@gmail.com 
Dr Dhara Roy  Sardar Vallabhbhai Patel (SVP) Hospital, Department of Medicine  "Room no 1036, Medicine department 1st floor, A2 wing, SVP Hospital, Department of Medicine, Near Ellisbridge, Ahmedabad, Gujarat-380006"
Ahmadabad
 
7600032882

dharabhavesh@gmail.com 
Dr Chakradhararao Guduri  Sidhhartha Medical college and Govt. General Hospital  Ring road, Gundala, Vijayawada, Andhra Pradesh 520008.
Krishna
 
9440231369

profguduri@gmail.com 
Dr Rakesh Bhadade  Topiwala National Medical College & Nair Hospital  Dr. A. L. Nair road, Mumbai 400008
Mumbai
 
9820394620

rakeshbhadade@gmail.com 
Dr N Kumarasamy  VHS-Infectious Diseases Medical Centre, Chennai  SH 49A, Pallipattu, Tharamani, Chennai, Tamil Nadu 600113
Chennai
 
9176912007

kumarasamy@cartcrs.org 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 29  
Name of Committee  Approval Status 
Institutional Ethics Committee, Gandhi Medical College and Hospital, Musheerabad, Secunderabad, Hyderabad, Telangana - 500003 India  Approved 
AIIMS Rsishikesh Institutional Ethics Committee  Approved 
Human Research Ethics Committee, Goverment Medical College, Surat  Approved 
Instittutional Ethics Committee BJ Medical College and General Hospital  Approved 
Institute Ethics Committee ,All India Institute of Medical Sciences, Old OT Block, New Delhi  Approved 
Institutional Ethics Committe Armed Forces Medical College,Solapur Road, Pune  Approved 
Institutional Ethics Committe PDU Medical College Rajkote Human   Approved 
Institutional Ethics Committee  Approved 
Institutional Ethics Committee Yashwantrao Chavan Memorial Hospital, Piimpri  Approved 
Institutional Ethics Committee BVDU  Approved 
Institutional Ethics Committee Siddhartha Medical College and Goverment General Hospital Vijayawada  Approved 
Institutional Ethics Committee, Goverment Medical College, Nagpur  Approved 
Institutional Ethics Committee, Institue of Advanced Research In Health Sciences, Tamil Nadu Goverment MultiSpeciality Hospital, Omandurar Goverment Estate, Chennai  Approved 
Institutional Ethics Committee, Institue of Advanced Research In Health Sciences, Tamil Nadu Goverment MultiSpeciality Hospital, Omandurar Goverment Estate, Chennai  Approved 
Institutional Ethics Committee, PD Hinduja Hospital  Approved 
Institutional Ethics Committee, TNMC & NAIR HOSPITAL MUMBAI  Approved 
Institutional Ethics Committee,BJ Medical College and Civil Hospital, Ahemdabad, Gujrat  Approved 
Institutional Ethics Committee-AIIMS Jodhpur  Approved 
Institutional Ethics Committee-Clinical Studies Apollo Hospitals  Approved 
Institutional Ethics Committee-Clinical Studies Apollo Hospitals  Approved 
Institutional Human Ethics Committee, AIIMS BHOPAL  Approved 
Institutional Human Ethics Committee,GMERS Medical College and Hospital, Gotri Vadodara   Approved 
Kolhapur Cancer Centre Institutional Ethics Committee  Approved 
MAX HEALTHCARE ETHICS COMMITTEE  Approved 
NARI Ethics Committee  Approved 
NHL Institutional Ethics Committee  Approved 
Office of Ethics Committee SMS Medical College and Attached Hospitals Jaipur  Approved 
Office of Research Institutional Review Board, Christian Medical College, Vellore  Approved 
VHS Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  Coronavirus as the cause of diseases classified elsewhere 
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  chloroquine or hydroxychloroquine   local standard of care plus chloroquine or hydroxychloroquine (two oral loading doses, then orally twice daily for 10 days)  
Comparator Agent  Local standard of care  Local standard of care 
Intervention  Lopinavir with Ritonavir (ditto) plus Interferon   Local standard of care plus Lopinavir with Ritonavir ((orally twice daily for 14 days) plus Interferon (daily injection for 6 days). 
Intervention  Lopinavir with Ritonavir (orally twice daily for 14 days)   Local standard of Care plus Lopinavir with Ritonavir (orally twice daily for 14 days)  
Intervention  Remdesivir   local standard of care plus Remdesivir (daily infusion for 10 days)  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1. Adults (aged ≥18 years) hospitalized with definite COVID-19
2. Not already receiving any of the study drugs
3. Without known allergy or contraindications to any of them (in the view of the physician responsible for their care)
4. Without anticipated transfer within 72 h to a non-study hospital

Patients invited to join the study will be those who are admitted to a collaborating hospital; no wider recruitment efforts are expected 
 
ExclusionCriteria 
Details  1. Any of the available study drugs are contra-indicated (e.g. because of patient characteristics, chronic liver or heart disease, or some concurrent medication)
2. Pregnant
3. Declined to participate in the study

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
All-cause mortality, subdivided by the severity of disease at the time of randomization, measured using patient records throughout the study  Throughout the study 
 
Secondary Outcome  
Outcome  TimePoints 
Measured using patient records:
1. Duration of hospital stay (hours)
2. Time to first receiving ventilation (or intensive care) (hours) 
Measured using patient records:
1. Duration of hospital stay (hours)
2. Time to first receiving ventilation (or intensive care) (hours) 
 
Target Sample Size   Total Sample Size="7000"
Sample Size from India="1500" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   01/05/2020 
Date of First Enrollment (Global)  26/03/2020 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   Publication and dissemination plan This international collaboration is co-ordinated through the World Health Organization, which is also a sponsor of the trial. Any wholly reliable interim findings will be disseminated rapidly by the WHO. There will be group authorship recognizing the contribution of all national and local investigators and guided by the International Committee of Medical Journal Editors (ICMJE) recommendations. IPD sharing statement: The current data sharing plans for this study are unknown and will be available at a later date. 
Brief Summary  

COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
There are currently no available vaccines or treatments for COVID-19. Although there have been some suggestions for untested treatments that could be added to  the usual care in hospitals, none is known to help. The World Health Organization (WHO) is, therefore, organizing a study in many countries in which some of these untested treatments are compared with each other, to discover whether any do help. The study treatments are remdesivir,  hydroxychloroquine, lopinavir plus ritonavir, and interferon-beta. Some are given as daily pills, and some as daily injections.

 

CTRI Number  CTRI/2020/04/024858 [Registered on: 25/04/2020] Trial Registered Prospectively
Last Modified On: 25/04/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Non-randomized, Active Controlled Trial 
Public Title of Study   “To study the effectiveness of Ivermectin with standard of care treatment versus standard of care treatment for COVID 19 cases. A Pilot Study 
Scientific Title of Study   “To study the effectiveness of Ivermectin with standard of care treatment versus standard of care treatment for COVID 19 cases. A Pilot Study 
Secondary IDs if Any  
Secondary ID  Registry 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Sandeep Budhiraja 
Address  Max Super Speciality Hospital (DDF), East Block, Internal Medicine department, 2- Press Enclave Road, New Delhi

New Delhi
DELHI
110017
India 
Phone    
Fax    
Email  sbudhiraja@maxhealthcare.com  
 
Details Contact Person
Scientific Query

Modification(s)  
Name  Dr Ram Shankar Mishra 
Address  Max Super Speciality Hospital (DDF), East Block, Internal Medicine Department, 2- Press Enclave Road, New Delhi

New Delhi
DELHI
110017
India 
Phone  9810193145  
Fax    
Email  docmishra@yahoo.co.in  
 
Details Contact Person
Public Query

Modification(s)  
Name  Rajesh Saxena 
Address  Max Super Speciality Hospital (DDF), East Block, Service Floor, 2- Press Enclave Road, New Delhi

New Delhi
DELHI
110017
India 
Phone  9818474003  
Fax    
Email  rajesh.saxena@maxhealthcare.com  
 
Source of Monetary or Material Support
Modification(s)  
Max Super Speciality Hospital (DDF) Saket 
 
Primary Sponsor  
Name  Max Super Speciality Hospital A Unit of Devki Devi Foundation 
Address  2, Press Enclave Road, Saket, New Delhi-17 
Type of Sponsor  Private hospital/clinic 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 1  
Contact Person  Name of Site  Site Address  Phone/Fax/Email 
Dr Sandeep Budhiraja  Max Super Speciality hospital, Saket (A unit of Devki Devi Foundation)  Department of Internal Medicine, 2, Press Enclave Road, Saket, New Delhi-17
New Delhi
 
9810262954

sbudhiraja@maxhealthcare.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Other specified viral diseases 
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Ivermectin  Cases of COVID 19 shall be treated with Ivermectin 200 to 400mcg per kg body weight on day 1 and day 2 along with standard treatment of the hospital protocol 
Comparator Agent  Standard treatment as per hospital protocol for COVID 19  Cases of COVID 19 shall be treated with standard treatment as per hospital protocol for COVID 19 until the recovery. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1. Subjects within age group between 18 to 75 years
2. With either sex, male or female
3. Confirmed case of COVID-19 at Max Hospitals. 
 
ExclusionCriteria 
Details  Patients who are critically sick  
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment    
Blinding/Masking   Open Label 
Primary Outcome
Modification(s)  
Outcome  TimePoints 
This study aims to confirm the antivirus effectiveness of Ivermectin on coronavirus i.e COVID 19
then to explore its potential use in the combating to the COVID 19 pandemics.  
Viral load will be monitored at 1, 3 & 5 days from beginning of trial drug (48 hours interval) Until the report comes negative. Drug will be delivered on daily basis upto eradication of virus or completion of
the trial 
 
Secondary Outcome
Modification(s)  
Outcome  TimePoints 
Safety of the drug vs standard care of treatment will be checked   Treatment will be provided until the eradication of virus or completion of
the trial. 
 
Target Sample Size   Total Sample Size="50"
Sample Size from India="50" 
Phase of Trial   N/A 
Date of First Enrollment (India)
Modification(s)  
25/04/2020 
Date of First Enrollment (Global)  No Date Specified 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details    
Brief Summary   Coronavirus disease (COVID-19) is an infectious disease caused by a new virus. The disease causes respiratory illness (like the flu) with symptoms such as a cough, fever, and in more severe cases, difficulty breathing. At present, there are no specific treatments for COVID-19. WHO recommends four treatments for COVID 19 with drugs i.eRemdesivir, Lopinavir/ ritonavir, Lopinavir/ ritonavir with interferon beta -1a, and chloroquine or hydroxychloroquine. Currently, there are several ongoing clinical trials evaluating potential treatments. Recently, LeonCaly report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARSCoV-2 able to effect ∼5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrant further investigation for possible benefits in humans. The study rationale is to understand the effect of the drug on eradication of virus. This study aims to confirm the antivirus effectiveness of Ivermectin on coronavirus i.e COVID 19 then to explore its potential use in the combating to the COVID 19 pandemics.

Enrollment of subject into the trial shall only occur after providing written permission to voluntarily participate into the study by signing and dating the informed consent form before starting any trial related treatment. 50 cases of COVID-19 will be enrolled into the trial. The trial shall be divided into two groups. First group with 25 confirmed cases of COVID 19 shall be treated with Ivermectin 200 to 400mcg per kg body weight on day 1 and day 2 along with standard treatment of the hospital protocol. The second group with 25 confirmed cases of COVID 19 shall be treated with standard treatment as per hospital protocol for COVID 19. Subjects in both the arms shall be followed up for recovery of death with regular monitoring as per below schedule. 

 Test for virus at 1, 3 & 5 days from beginning of trial drug started for the patient in the hospital 
 Clinical profile of the patient every day of hospitalization 
 Investigation of pulmonary function and O2 saturation every day of hospitalization 
 The day a patient is put on ventilator and the day when removed 
 The day a patient develops acute respiratory distress syndrome and the day when relieved 

All the above data shall be collected on paper case record form for interim and final analysis from start of the trial i.e enrolment, treatment and follow-up. Viral test to monitor the eradication of Virus shall be done free of cost from third day of enrollment and providing the study drug on daily basis upto eradication of virus or completion of the trial.
 

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