Radical cure for vivax malaria in Indonesia
| ISRCTN | ISRCTN38290380 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN38290380 |
| Secondary identifying numbers | Vivax-Primaquine-ACT-QN/Oxtrec 29-10 |
- Submission date
- 01/05/2012
- Registration date
- 08/05/2012
- Last edited
- 25/04/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Malaria is a serious tropical disease caused by a Plasmodium parasite (e.g., P. vivax and P. falciparum) spread by mosquitoes. Antimalarial medication is used to prevent and treat malaria. The current standard treatment in Indonesia for P. vivax malaria is oral artesunate combined with amodiaquine plus primaquine for 14 days. The aim of this study is to measure the effectiveness of primaquine against P. vivax malaria relapses when combined with dihydroartemisinin-piperaquine or quinine.
Who can participate?
Men aged between 18 and 60 in the Indonesian Army who have just returned from deployment at Papua and have P. vivax infection
What does the study involve?
Participants are asked to stay on the base for at least 28 days and are randomly allocated to one of the following three treatments: artesunate alone, quinine combined with primaquine, or dihydroartemisinin-piperaquine (DHA-PQP) plus primaquine. For DHA-PQP, primaquine is given 26 days after the participant finishes the DHA-PQP. The follow up lasts for one year. The participants are closely observed by doing routine tests including measurement of vital signs, blood samples, and ECG (heart rhythm) examinations. Malaria relapse rates and the effectiveness of the treatments are compared.
What are the possible benefits and risks of participating?
The findings will guide decisions about new treatments for vivax malaria globally. The main benefit is that participants are given effective drugs and are closely monitored for safety and relapse. There are two main risks in this study: drug side effects and the risk of contracting malaria. In general, these drugs are well tolerated, although in some cases side effects could occur.
Where is the study run from?
1. University of Indonesia (Indonesia)
2. Eijkman Institute (Indonesia)
3. Eijkman Oxford Clinical Research Unit (EOCRU) (Indonesia)
4. Indonesian Army Medical Corps (Indonesia)
When is the study starting and how long is it expected to run for?
November 2010 to April 2012
Who is funding the study?
1. Medicines for Malaria Venture (MMV) (Switzerland)
2. Eijkman Oxford Clinical Research Unit (EOCRU) (Indonesia)
Who is the main contact?
Prof. Inge Sutanto
sutanto.inge@yahoo.com
Contact information
Scientific
Parasitology Dept, Faculty of Medicine
University of Indonesia
Jakarta
10430
Indonesia
| sutanto.inge@yahoo.com |
Study information
| Study design | Single-center randomized open-label non-inferiority study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Efficacy of primaquine against Plasmodium vivax relapses when combined with dihydroartemisinin-piperaquine or quinine in Indonesian soldiers |
| Study hypothesis | The study aims to characterize the safety, tolerability, efficacy and pharmacokinetics of dihydroartemisinin-piperaquine (DHA-PQP) for the radical cure of P. vivax when combined with 14 days of primaquine. |
| Ethics approval(s) | 1. Medical Research Ethics Committee of Faculty of Medicine, University of Indonesia, 02/08/2010, ref: 328/PT02.FK/ETIK/2010 2. Oxford Tropical Research Ethics Committee, 28/09/2010 3. Clinical Trial Clearances from Indonesian FDA, 25/10/2010, ref: PN.01.06.1.31.10.10.10199 |
| Condition | Malaria |
| Intervention | A single center randomized open label non-inferiority study of PQ treatment against the cumulative relapse rate over 1 year when administered with two different companion blood schizontocides as radical cure of vivax malaria. Enrolled subjects were randomly assigned to one of the following arms: 1. QN+PQ = standard quinine therapy (Q™, 200 mg quinine/tablet; Kimia Pharma, Bandung, Indonesia) of 200mg base three times daily for 7 days plus concurrent dosing with 0.5mg/kg primaquine base once daily for 14 days (Malafree™; 15mg primaquine base/tablet; Shin Poon Pharmaceuticals, Seoul, South Korea) 2. DHA-PP+PQ = combined dihydroartemsinin plus piperaquine (Euartesim™, Sigma Tau, Italy; DHA-PP; 40mg dihydroartemisinin base and 320mg of piperaquine base per tablet) of three tablets for participants < 75kg, or four tablet for participants > 75kg for three days, followed by 0.5mg/kg primaquine daily for 14 days commencing on day 28 after enrollment (no safety data guided co-administration of primaquine with DHA-PP) 3. AS alone = artesunate alone (Arsuamoon™, tablet of 50mg artesunate packaged with tablet of 196mg amodiaquine hydrochloride; Guilin Pharmaceuticals Co. Ltd, Shanghai, China) was administered in a total dose of 200mg on day of enrollment, followed by a single daily dose for 6 more days Follow up was for 365 days, counting the first day of study drug administration as Day 0. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Dihydroartemisinin-piperaquine, quinine, primaquine, artesunate, amodiaquine |
| Primary outcome measure | Measure and compare, using a non-inferior design, the cumulative relapse rate over one year of the two arms relative to the natural relapse rate |
| Secondary outcome measures | Measure the efficacy of the two primaquine combination regimens against relapse, relative to the relapse rate of the artesunate alone regimen. Relapse efficacy is defined as: 100% x natural relapse rate - relapse rate post-PQ/natural relapse rate |
| Overall study start date | 01/11/2010 |
| Overall study end date | 10/04/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target number of participants | 80 participants per arm, total 240 participants. |
| Participant inclusion criteria | 1. Male patients between the age of 18 and 60 years 2. Traveled for >1 month to north eastern Papua within the past 12 months 3. Body weight > 40 kg and ≤ 90 kg 4. Presence of P. vivax parasitemia mono- or mixed infection with another plasmodial species confirmed by positive microscopy of P. vivax with parasite density ≥20/ µL of blood 5. Written informed consent provided by patient. If the patient was unable to write, witnessed consent was permitted 6. Glucose-6-phosphate dehydrogenase (G6PD) normal using the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) qualitative fluorescent spot test (Trinity Biologicals, USA) 7. Able to swallow oral medication 8. Able and willing to participate based on information given to patient |
| Participant exclusion criteria | 1. Presence of clinical condition requiring hospitalization 2. Presence of significant anaemia, as defined by Hb < 8 g/dL 3. G6PD deficient determined by a standard qualitative test 4. Definite plans for an absence of 3 days or more from the base within 28 days of being enrolled 5. Known history or evidence of clinically significant disorders: 5.1. Cardiovascular 5.2. A corrected QT interval (QTc) >450 ms* 5.3. Respiratory, including active tuberculosis 5.4. Hepatic 5.5. Renal 5.6. Gastrointestinal 5.7. Immunological 5.8. Neurological, including hearing impairment 5.9. Endocrine 5.10. Infectious 5.11. Malignancy 5.12. Psychiatric 6. Recent head trauma 7. Any other clinically significant finding that the investigator judges will place the patient at risk or interfere with the study results 8. Known to have or be confirmed: 8.1. Active Hepatitis A (e.g. by detection of anti HAV-IgM) 8.2. Hepatitis B surface antigen (HBsAg) carrier 8.3. Hepatitis C antibody (HCV Ab). 9. Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range 10. Renal impairment as indicated by abnormal creatinine clearance of < 60 ml/min, measured using Cockcroft-Gault formula 11. Known history of hypersensitivity, allergy or adverse reactions to piperaquine, quinine or primaquine, artesunate, dihydroartemisinin (DHA) or other artemisinins 12. Previous participation in the present clinical trial with DHA/PQP 13. Had received any investigational drug within the past 4 weeks |
| Recruitment start date | 01/11/2010 |
| Recruitment end date | 10/04/2012 |
Locations
Countries of recruitment
- Indonesia
Study participating centre
10430
Indonesia
Sponsor information
Hospital/treatment centre
Jl. Diponegoro No. 69
Jakarta
10430
Indonesia
| Phone | +62 (0)21 391 0414 |
|---|---|
| kbaird@eocru.org | |
| Website | http://www.eijkman.go.id/ |
Funders
Funder type
Research organisation
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- MMV
- Location
- Switzerland
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/03/2013 | Yes | No |
Editorial Notes
25/04/2017: Plain English summary added.
