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CTRI Number  CTRI/2022/12/048283 [Registered on: 20/12/2022] Trial Registered Prospectively
Last Modified On: 29/10/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Comparison of 7 day vs 14 day treatment of Primaquine for Plasmodium vivax malaria 
Scientific Title of Study   A multi-center randomized controlled trial to compare the efficacy, safety, and tolerability of high dose, short course Primaquine–A pilot study  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Nitika 
Designation  Scientist E 
Affiliation  ICMR-National Institute of Malaria Research 
Address  ICMR- National Institute of Malaria Research Sector 8, Dwarka New Delhi 110077 India

South West
DELHI
110077
India 
Phone    
Fax    
Email  dr.nitika11@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Praveen Bharti 
Designation  Scientist E 
Affiliation  ICMR-National Institute of Malaria Research 
Address  ICMR- National Institute of Malaria Research Sector 8, Dwarka New Delhi 110077 India

South West
DELHI
110077
India 
Phone    
Fax    
Email  saprapbs@yahoo.co.in  
 
Details of Contact Person
Public Query  
Name  Dr Manju Rahi 
Designation  Scientist F 
Affiliation  Indian Council of Medical Research 
Address  Indian Council of Medical Research, AIIMS Campus, Ansari Nagar New Delhi 110029 India

South West
DELHI
110029
India 
Phone    
Fax    
Email  drmanjurahi@gmail.com  
 
Source of Monetary or Material Support  
Infectious Disease Data Observatory, Oxford and National Institute of Malaria Research, New Delhi 
 
Primary Sponsor  
Name  ICMR National Institute of Malaria Research 
Address  Sector 8, Dwarka New Delhi 110077 India 
Type of Sponsor  Research institution 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr KJ Upadhayay  Ahmedabad Municipal Corporation Hospital  Christian colony, Satyanagar,Jamalpur, Ahmadabad Gujarat-380022
Ahmadabad
GUJARAT 		 9825362253

drkjupadhyay@hotmail.com 
Dr Rajendra Kumar Baharia  Ahmedabad Municipal Corporation Hospital  Christian colony, Satyanagar, jamalpur, Ahmadabad Gujarat 380022
Ahmadabad
GUJARAT 		 7726986307

rajendrabaharia@gmail.com 
Dr Syed Mohammad Naser  Calcutta National Medical College and Hospital  32 Gorachand Road, Kolkatta-14 West Bengal, India
Kolkata
WEST BENGAL 		 9433349332

smnaser2012@gmail.com 
Dr Nitika  ICMR-National Institute of Malaria Research  Sector 8 Dwarka 110077 New Delhi, India
South West
DELHI 		 9779249665

dr.nitika11@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
BJ Medical College Ethics Committee  Approved 
Ethics Committee, Calcutta National Medical College  Approved 
Institutional Ethics Commitee, ICMR-NIMR  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: B519||Plasmodium vivax malaria without complication,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Primaquine 0.25 mg/kg/day  Primaquine 0.25 mg/kg/day for 14 days given once a day orally 
Intervention  Primaquine 0.50mg/kg/day  Primaquine 0.50mg/kg/day for 7 days given once a day orally 
 
Inclusion Criteria  
Age From  16.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1.P. vivax (asexual) malaria monoinfection confirmed by microscopy on a thin and thick blood smear
2.Age 16 years and over of either gender.
3.Fever > 37.5°C axillary, or a history of fever within 48 hours
4.Female patients of child-bearing potential are included if they are non-lactating and willing to use contraceptive methods during the study period. Non-child bearing potential defined as:
4.1 post-menopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL), pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation with medical report verification or,
4.2 Child-bearing potential, has a negative urine pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study drug:
4.2.1 Use of oral contraceptive, either combined or progesterone alone (if no contraindications to oral contraceptives exist).
4.2.2 Barrier contraceptive if oral contraceptives are contraindicated
4.2.3 Use of an intrauterine device.
5.Willing to give informed consent.
6.Willing to comply with protocol instructions and duration of follow up.
7.Only patients living in and around the site facilities will be enrolled in the study to facilitate follow-up.
 
 
ExclusionCriteria 
Details  1.Patients with G6PD activity less than 30% of the adjusted male median (AMM), tested by UV spectrophotometry.
2.Patients with mixed infection with P. vivax and P. falciparum (e.g. identified by Giemsa-stained smear or rapid diagnostic test).
3.Patient with body weight less than 40 kg.
4.Severe P. vivax malaria defined as per Indian National Guidelines criteria (Appendix I).
5.Haemoglobin <8 g/dl to be measured by Hb auto analyser.
6.Cannot tolerate oral treatment
7.History of haemolytic anaemia or methemoglobinemia or blood transfusion within 90 days
8.Pregnant and lactating females.
9.Known allergy to chloroquine, primaquine or any other related drugs.
10.Evidence of gastro-intestinal dysfunction that could alter absorption or motility (e.g., diarrhoea defined as >3 episodes of watery stools in the previous 24 h or patients who have had three episodes of vomiting within 24 h prior to screening).
11.Use of concomitant medications that could induce haemolysis or haemolytic anaemia or depressants of myeloid element of the bone marrow.
12.Any anti-malarial treatment taken 1 month prior to enrolment.
13.Ongoing prophylaxis with drugs having anti-malarial activity
14.Participation in any other investigational drug study of at least 3 months prior to screening
15.Any other underlying disease that could compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, HIV, Hepatitis, tuberculosis, Splenectomy conducted earlier as confirmed by history or clinical examination; evidence of clinically significant cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, or endocrine diseases, malignancy, or other abnormalities.
16.Retinal/visual field defects or auditory defects and history of psoriasis and porphyria.
 
 
Method of Generating Random Sequence   Permuted block randomization, fixed 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
•The incidence risk of symptomatic P. vivax malaria
 		 Month 6
 
 
Secondary Outcome  
Outcome  TimePoints 
The incidence risk of any (symptomatic and asymptomatic) P. vivax malaria  Day 28, till month 6 
The proportion of patients vomiting their medication   Within 1 hour of administration 
The proportion of adverse events and serious adverse events  throughout study period 
The incidence risk of severe anaemia (Hb 8g/dl) and/ or the risk of blood transfusion  throughout study period 
Risk of greater than 25% fall in haemoglobin on any day of treatment  throughout study period 
Gastrointestinal (GI) tolerability - incidence of abdominal pain, heartburn, diarrhoea, constipation, nausea and vomiting  throughout study period 
Ophthalmic safety - incidence of corneal deposits, retinal and visual field abnormalities.   throughout study period 
 
Target Sample Size   Total Sample Size="400"
Sample Size from India="400" 
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 3/ Phase 4 
Date of First Enrollment (India)   01/04/2023 
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="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details   NA 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - YES
  1. What data in particular will be shared?
    Response (Others) -  Individual participant data will be shared after deidentification with Infectious Diseases Data Observatory as they pool all malaria data to improve the power of research results. In the websites eg CTRI as required by the law in India, the data will include a summary of the results.

  2. What additional supporting information will be shared?
    Response -  Study Protocol
    Response -  Statistical Analysis Plan
    Response (Others) -  CRF
  3. Who will be able to view these files?
    Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.

  4. For what types of analyses will this data be available?
    Response - For individual participant data meta-analysis.

  5. By what mechanism will data be made available?
    Response (Others) -  To gain access data requestors will need to sign a data access agreement. Data will be available on the Oxford University Platform www.iddo.org

  6. For how long will this data be available start date provided 01-12-2024 and end date provided 01-12-2027?
    Response - Beginning 9 months and ending 36 months following article publication.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - NA
Brief Summary
Modification(s)  

Plasmodium vivax malaria is an important public health concern. In 2020, the WHO Southeast asia region reported 2% of the global malaria burden and India shouldered 83% of the cases in the region. Although the Southeast asia region have reported a 75% reduction in malaria deaths from 35000 in 2000 to 9000 in 2020, India accounted for 82% of these deaths; a large number for a curable disease.1 Out of the total 1,90,000 malaria cases reported in India in 2020, 70,000 were caused by P. vivax. P. vivax infections prove to be a substantial challenge for malaria control and elimination targets because of the ability of P. vivax to cause relapse infections. Relapse results from activation of dormant liver stages (hypnozoites) and can occur weeks or months following an acute infection. Recurrent infections are usually associated with a febrile illness, a cumulative risk of severe anaemia, direct and indirect mortality, and these relapses are the most important source of onward transmission of the parasite. The only hypnozoitocidal (capable of clearing the intra-hepatic schizonts and hypnozoites of P. vivax) drug that is widely available and licensed for use for P. vivax radical cure regimens in India is primaquine (PQ). PQ is an 8-aminoquinoline compound with the potential of causing severe drug-induced haemolysis in glucose-6-phosphate-dehydrogenase (G6PD) deficient patients and has to be given with caution. The Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends a radical cure regimen comprising of 0.25 mg/kg body weight for 14 days equivalent to a total dose of 3.5 mg/kg. PQ has a narrow therapeutic index and a short elimination half-life of about 4-7 hour.2 Thus, PQ requires daily administration for up to 2 weeks for optimum action but this may result in poor compliance. This poor compliance may increase the chances of relapse occurring after weeks, months, or years.3 The current regimen poses the problems of low adherence and reduced effectiveness because of long duration, hence there is a need to reconsider and evaluate a higher daily dose. The daily dose however is limited by the potential risk of hemolysis and tolerability. The treatment can be given over 7 days at 0.50 mg/kg body weight, so that the total dose remains the same. This prospective clinical study is proposed to compare and evaluate the efficacy of two radical cure regimens in the treatment of P. vivax malaria in India.

  1. World Malaria Report 2021. Available on https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021 Accessed on 13th March 2022
  2. Saravu K et al.A pilot randomized controlled trial to compare the effectiveness of two 14-day primaquine regimens for the radical cure of vivax malaria in South India. Malaria journal.2018;17(1):1-11
  3. Fernando, D., C. Rodrigo, and S. Rajapakse, Primaquine in vivax malaria: an update and review on management issues. Malaria journal.2011;10(1):1-12.


 
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