| CTRI Number |
CTRI/2021/12/038778 [Registered on: 21/12/2021] Trial Registered Prospectively |
| Last Modified On: |
09/02/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
comparative clinical trial to evaluate safety and efficacy of test drug plus standard of care and standard of care alone in COVID 19 Acute Respiratory Distress Syndrome (ARDS) patients with non-invasive ventilation. |
|
Scientific Title of Study
|
A multicentre, prospective, open label, randomized comparative clinical trial to evaluate safety and efficacy of Reliance Life Sciences’ Bevacizumab (R-TPR-023) plus standard of care and standard of care alone in COVID 19 Acute Respiratory Distress Syndrome (ARDS) patients with non-invasive ventilation. |
| Trial Acronym |
R002 |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| RLS/RES/2021/05, Version 2.0 dated 03 Sep 2021 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Ajay Kumar Yadav |
| Designation |
Head - Clinical Research Services |
| Affiliation |
Reliance Life Sciences Pvt Ltd |
| Address |
RLS Bio - Product Trials Group, Dhirubhai Ambani Life Sciences
Centre (DALC) R-282, TTC Area of MIDC, Thane - Belapur Road,
Rabale, Navi Mumbai
Thane
MAHARASHTRA
400701
India |
| Phone |
9820804218 |
| Fax |
|
| Email |
Ajaykumar2.Yadav@relbio.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Sachin Kagne |
| Designation |
Medical Monitor |
| Affiliation |
Reliance Life Sciences Pvt Ltd |
| Address |
RLS Bio - Product Trials Group, Dhirubhai Ambani Life Sciences
Centre (DALC) R-282, TTC Area of MIDC, Thane - Belapur Road,
Rabale, Navi Mumbai
Thane
MAHARASHTRA
400701
India |
| Phone |
9987885679 |
| Fax |
|
| Email |
Sachin.Kagane@relbio.com |
|
Details of Contact Person
Public Query
|
| Name |
Sachin Singh |
| Designation |
Head - Clinical Operations |
| Affiliation |
Reliance Life Sciences Pvt Ltd |
| Address |
RLS Bio - Product Trials Group, Dhirubhai Ambani Life Sciences
Centre (DALC) R-282, TTC Area of MIDC, Thane - Belapur Road,Rabale, Navi Mumbai
Thane
MAHARASHTRA
400701
India |
| Phone |
9004246165 |
| Fax |
|
| Email |
Sachin2.Singh@relbio.com |
|
|
Source of Monetary or Material Support
|
| RLS Bio - Product Trials Group, Dhirubhai Ambani Life Sciences
Centre (DALC) R-282, TTC Area of MIDC, Thane - Belapur Road,
Rabale, Navi Mumbai 400701, Maharastra, India |
|
|
Primary Sponsor
|
| Name |
Reliance Life Sciences Pvt Ltd |
| Address |
Dhirubhai Ambani Life Sciences Centre (DALC), R-282, TTC Area of
MIDC, Rabale, Navi Mumbai – 400701, Maharashtra, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Dipu T S |
Amrita Institute of Medical Sciences |
Department of General Medicine and Infectious Diseases
Amrita Institute of Medical Sciences
Ernakulam
KERALA |
4842851234
4842852020
diputsmck@gmail.com |
| Dr Biplabendu talukdar |
Medical College and Hospital |
4th Floor, 88 College Street
Kolkata
WEST BENGAL |
03322551621
drbiplabendutalukder@gmail.com |
| Dr Anand Nikalje |
MGM Medical College & Hospital |
Department of medicine, 2nd floor, N-6 Cidco, 431003
Aurangabad
MAHARASHTRA |
0240-6601100
dranandnikalje68@gmail.com |
| Dr Badal Sahu |
NRS Medical College and Hospital, Department of Medicine |
38, AJC Bose Road,700014
Kolkata
WEST BENGAL |
033-22860140
drbadal08@gmail.com |
| Dr C Premdeep |
PREM CHEST HOSPITAL |
Sunday Market line Pogathota 5240O1, India.
Nellore
ANDHRA PRADESH |
8612326892
8612320232
premdrswetha@gmail.com |
| Dr M Manojkumar |
VIJAYA SUPER SPECIALITY Hospital |
OPD Room NO: 04
Pogathota
Nellore
ANDHRA PRADESH |
0861-23218828
0861-2300068
manojkumarmddec@gmail.com |
| Dr Sushant Shinde |
Vishwaraj Hospital, Consultant physician, Intensive, & Diabetologist |
Ground floor, OPD no.1, Pune Solapur Road, Near Loni Kalbhor Railway
Station, Kadamwakwasti 412201
Pune
MAHARASHTRA |
9615057070
drsushantshinde1983@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Ethics Committee, NRS Medical College and Hospital, Department of Medicine, 138, AJC Bose Road, Kolkata 700014, West Bengal, India |
Approved |
| Institutional Ethics Committee for Human Research, Medical College, 88 College Street, Kolkata 700073, West Bengal, India |
Approved |
| Institutional Ethics Committee MAEERS Vishwaraj Hospital Gate No499, Kadamwakwasti Loni Kalbhor, Solapur Road, Pune, 412202, Maharashtra, India |
Approved |
| lnstitutional Ethics Committee, Amrita Institute of Medical Sciences, AIMS- Ponekkara, Kochi , Edappally, Ernakulam, Kerala |
Approved |
| MGM Ethics Committee for Research on Human Subjects MGM Campus, N-6 Cidco,Aurangabad, 431 003, Maharashtra, lndia |
Approved |
| VIJAYA ETHCS COMMITTEE Vijaya Super Speciality Hospital, 16-II/41 A, Raghava Cine Complex Road Pogathotz, Nellore, Andhra Pradesh -524001 , India |
Approved |
| VIJAYA ETHCS COMMITTEE Vijaya Super Speciality Hospital, 16-II/41 A, Raghava Cine Complex Road Pogathotz, Nellore, Andhra Pradesh -524001 , India |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
0.9% NacL (100 ML) |
Day 0, standard of care alone group would receive only 100 ml of 0.9% NaCl |
| Intervention |
R-TPR-023 |
Day 0, It is administered as intravenous infusion in dose of 500 mg Bevacizumab should be mixed with 100 ml of 0.9% NaCl( standard of care). |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Age: ≥18 – ≤65 years old, male and female patients hospitalized for Covid 19 infection.
2. Recently admitted in ICU (i.e. Enrollment/Randomization should occur within 48 hours of ICU admission).
3. Radiologically confirmed pneumonia.
4. Laboratory confirmed Covid19 infection.
5. Severe COVID 19 pneumonia with ARDS defined as patients with clinical signs of pneumonia plus one of the following:
a. respiratory rate >30 breaths/min
b. severe respiratory distress or SpO2 <90% on room air.
6. Patients on different modalities of oxygen therapy – High Flow Nasal Cannula Oxygen (>0.4 FiO /30 L/min of oxygen flow) or non-invasive ventilation.
7. Presence of raised inflammatory markers in any one of the following: CRP (CRP> 75 mg/L) or Ferritin (≥ 5 times Upper Limit of Normal) or IL-6 (>40 pg/ml) or D dimer (>1.5 μgFEU/ml).
8. Procalcitonin in normal range (<0.3 μg/L).
9. Women of childbearing potential or men capable of fathering children must agree to use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study drug. Women of childbearing potential must test negative for pregnancy at screening. |
|
| ExclusionCriteria |
| Details |
1. Unable to obtain informed consent from subject or LAR.
2. Patients with ALT/AST ≥ 5 x upper limit of normal (ULN).
3. Patients with heart disease or clinical symptoms that cannot be well controlled, such as NYHA class II or above of cardiac insufficiency, unstable angina, myocardial infarction within one year, supraventricular or ventricular arrhythmias that need treatment or intervention.
4. Allergic to Bevacizumab and its components.
5. Treatment with immunosuppressive or immunomodulatory therapy (including bevacizumab) within the past 3 months.
6. Platelet count of < 1,00,000 /cmm or absolute neutrophil count (ANC) < 2000/cmm at screening
7. Respiratory failure due to other secondary infections /bacterial sepsis or evidence of multiorgan failure
8. Clinical or laboratory evidence of active tuberculosis or active secondary infections.
9. Subjects who are HIV, HBsAg, HCV test positive.
10. Pregnant women, lactating women and planned pregnancy.
11. Have participated in other clinical trials in the last 3 months or the investigator is of opinion that it is not in the best interest of patient to get enrolled in the study or any other condition wherein the patient participation would cause concerns about his / her safety. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Pre-numbered or coded identical Containers |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| 1. Cumulative Proportion of patients requiring mechanical ventilation (invasive mechanical ventilation or extracorporeal membrane oxygenation) or death by |
Day 28 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| 1. Cumulative Proportion of patients requiring mechanical ventilation (invasive mechanical ventilation or extracorporeal membrane oxygenation) or death by |
day14. |
| 2. The time to hospital discharge or readiness for discharge as assessed with the use of WHO eight-category ordinal scale (with categories ranging from 1 to 8. Higher categories indicating a worse condition) |
Day 0 to Day 28 (Any time in between) |
| 3. The time to at least a two-category improvement in clinical status relative to baseline on the WHO eight-category ordinal scale. |
Day 0 to Day 28 (Any time in between) |
| 4. The time to clinical failure (the time to death, mechanical ventilation, worsening by two categories from baseline on the eight category ordinal scale], or withdrawal [whichever occurred first]). |
Day 0 to Day 28 (Any time in Between) |
| 5. All-cause mortality. |
Day 0 to Day 28 (Any time in Between) |
| 6. Time to PaO2/FiO2 ratio greater than 200. |
Day o to Day 28 (Any time In Between) |
| 7. Proportion of patients whose clinical status on the World Health Organization 8point ordinal scale is as follows on day 28: Not hospitalized, no limitations on activities. |
Day 0 to Day 28 (Any time in Between) |
| 8. PaO2/FiO2 ratio on admission |
Day 2 and Day 7. |
| 9.SOFA (Sequential Organ Failure Assessment) score till patient is in ICU (at baseline |
Day 0, day 14 and 28 |
| 10. Days free of supplemental Oxygen |
since Day 0 |
| 11. Duration of hospitalization |
since Day 0 |
| 12. Duration of ICU admission |
since Day 0 |
| 13. Proportion of patients with non-invasive ventilation |
Day 0 to Day 28 (Any time in between) |
| 14. Duration of non-invasive ventilation |
Day 0 to Day 28 (Any time Between) |
| 15. Duration of invasive mechanical ventilation |
Day 0 to Day 28 (Any time In Between) |
| 16. Cumulative incidence of SAEs, Grade 3 and 4 AEs, ADR |
Day 0 to Day 28 (Any time In between) |
|
|
Target Sample Size
|
Total Sample Size="44"
Sample Size from India="44"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
30/12/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Severe Covid-19 infection is associated with hyperactive and dysregulated immune response predominantly marked by inflammatory markers like Ferritin, CRP, IL-6. In addition it is also observed that there is increased activity of Vascular Endothelial Growth Factor (VEGF). As different therapeutic options are tried, even agent that inhibits actions of VEGF – a monoclonal antibody- Bevacizumab is being tried for this purpose. In a study conducted at China and Italy i.e. Efficacy and tolerability of bevacizumab in patients with severe Covid-19, usage of Bevacizumab was found to have beneficial effects.
This study is planned therefore to evaluate safety and efficacy of Bevacizumab in severe COVID 19 patients. Bevacizumab of Reliance Life Sciences has undergone non clinical toxicology studies and clinical studies earlier and it has received the marketing authorization for indications like metastatic colorectal carcinoma, non-squamous non-small cell lung cancer etc. It is noted that bevacizumab is tried as off label use in management of Covid-19 ARDS however data is minimal. In view of above Reliance Life Sciences requests approval for phase II clinical trial in patients of COVID 19 Acute Respiratory Distress Syndrome (ARDS) with noninvasive ventilation.
It is planned to enroll 44 patients and randomly assign them in 1: 1 ratio to receive either RLS Bevacizumab plus standard of care or standard of care alone, so that each group will have 22 patients.
Study will be conducted in ICU Admitted patients, there can be overlap of Screening, Randomization and Dosing with Bevacizumab on the same day. Dosing should occur within 48 hours of ICU admission. Day on which Bevacizumab is administered, is considered as day 0. # Though labelled as visits, the trial participants being ICU admitted patients at enrolment, these may not be actual visits in true sense (unless patient is discharged before 28 days and after discharge visits site for scheduled visits)
|