In Vivo Efficacy of Artesunate-amodiaquine and Artemether-lumefantrine for the Treatment of Uncomplicated Falciparum Malaria: an Open-randomised, Non-inferiority Clinical Trial in South Kivu, DR Congo
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 288
- Primary Endpoint
- Percentage of children with adequate parasitological clearance after treatment of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL)
Study Overview
Brief Summary
This will be an open-randomised non-inferiority study to test the hypothesis that the risk of recurrent parasitaemia after 42 days is not worse in the group receiving the Artesunate-Amodiaquine (ASAQ) regimen than in the group receiving the Artemether-Lumefantrine (Coartem®) regimen. Children with uncomplicated malaria meeting the inclusion criteria will be enrolled (after their parent/caretaker has given informed consent), treated on site with the drugs under evaluation and followed-up for a period of 42 days. Drugs will be given under direct supervision, either at the clinic or at home. Follow-up shall consist of a fixed schedule of clinical and laboratory examinations. Based on clinical and laboratory findings, children will be classified as therapeutic failures (early or late) or adequate responders.
The proportion of cases experiencing an in vivo therapeutic failure during the follow-up period will provide an estimate of the efficacy of the drug regimens. A Polymerase Chain Reaction (PCR) analysis will be carried out to differentiate true recrudescence due to treatment failure from episodes of re-infection. This proposal is compliant with the latest WHO recommendations for anti-malarial efficacy monitoring in high, medium or low transmission zones11.
Detailed Description
3.1 STUDY DESIGN Children with uncomplicated malaria meeting the inclusion criteria will be enrolled (after their parent/caretaker has given informed consent), treated on site with the drugs under evaluation and followed-up for a period of 42 days. Drugs will be given under direct supervision, either at the clinic or at home. Follow-up shall consist of a fixed schedule of clinical and laboratory examinations. Based on clinical and laboratory findings, children will be classified as therapeutic failures (early or late) or adequate responders.
The proportion of cases experiencing an in vivo therapeutic failure during the follow-up period will provide an estimate of the efficacy of the drug regimens. A Polymerase Chain Reaction (PCR) analysis will be carried out to differentiate true recrudescence due to treatment failure from episodes of re-infection. This proposal is compliant with the latest WHO recommendations for anti-malarial efficacy monitoring in high, medium or low transmission zones11.
3.2 STUDY SITES The study site will be the MSF catchment area of Baraka health centres, MSF-OCA Baraka, South Kivu, DRC.
3.3 STUDY POPULATION The study population is children aged between 6 and 59 months with uncomplicated P. falciparum malaria. This age group was selected because it is considered the most vulnerable and is less likely to clear infections spontaneously compared to older children and adults. In hyper-endemic areas, they are the most at risk of dying from malaria.
3.4 DEFINITIONS 3.4.1 DEFINITION OF PARENT/CARETAKER The parent/caretaker is defined as the household member who is aged ≥ 18 years who cares for the patient and can give accurate information on all demographic and health issues related to the patient and is present at the time of the survey.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 6 Months to 59 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age between 6 and 59 months
- •Weight ≥ 5 Kg
- •Slide-confirmed infection with Plasmodium falciparum only (no mixed infections)
- •Asexual parasite density between 2000 and 200000/µl of blood
- •Measured axillary temperature ≥ 37.5°C
- •Ability to swallow oral medication
- •High probability of respecting the follow-up visits (residence within 1 hour walking distance from the OPD, no upcoming travel plans, etc.)
- •Informed consent from a parent or caretaker aged at least 18 years.
Exclusion Criteria
- •• General danger signs according to the WHO definition (Appendix 5.1.1)
- •Signs of severe/complicated malaria according to the WHO definition (Appendix 5.1.2)
- •Severe anaemia (haemoglobin < 5 g/dL)
- •Known history of hypersensitivity to any of the study drugs
- •Severe acute malnutrition (as defined by a weight-for-height below -3 Z-score and/or symmetrical oedemas involving at least the feet)
- •Concomitant febrile illness due to causes other than malaria with the potential to confound study outcome (measles, acute lower tract respiratory infection, otitis media, tonsillitis, abscesses, severe diarrhoea with dehydration).
- •Having received already a full course of the treatment (or one of the treatments) under study in the previous 28 days (as indicated by the parent/caretaker). Note that previous incomplete anti-malarial intake of treatments under study, or previous intake of anti-malarials not under study, are not exclusion criteria, but details of any such intake should be recorded carefully.
- •History of hypersensitivity reactions or contra-indications to any medicines being tested.
Arms & Interventions
Amodiaquine-Artesunate (ASAQ)
Treatment regimen consisted of Amodiaquine-Artesunate (ASAQ) fixed dose (FD) (Winthrop Sanofi Aventis), given as 1 tablet/day 3 days (5-8 kg 1 tab of 25mg artesunate/67.5 mg amodiaquine base, 9-17 kg 50 mg artesunate/135 mg amodiaquine base)
Intervention: Amodiaquine-Artesunate (ASAQ) (Drug)
Artemether-Lumefantrine (AL)
Treatment consisted of Artemether-Lumefantrine (AL) (Coartem, Novartis) given as six twice/daily doses over three days (5-14 kg 1tab of 20mg artemether/120mg lumefantrine BD, 15-24 kg 2tabs of 20mg artemether/120mg lumefantrine BD with fatty food).
Intervention: Artemether-Lumefantrine (AL) (Drug)
Outcomes
Primary Outcomes
Percentage of children with adequate parasitological clearance after treatment of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL)
Time Frame: 42 days
In a Kaplan Meyer survival curve it will be shown what the parasitological free period is for children treated with ASAQ or AL, uncorrected for PCR (reinfection and recrudescence) and PCR corrected (recrudescence only).
Secondary Outcomes
- The proportion of early therapeutic failures, late clinical failures and late parasitological failures in a period of 42 days after treatment initiation(42 days)
- Recommendations to MoH on choice of antimalarial first line drugs(42 days)
Investigators
Marit de Wit
Health Advisor
Medecins Sans Frontieres, Netherlands