Efficacy of Artesunate-amodiaquine and Artemether-lumefantrine for Uncomplicated Malaria in South Kivu, DR Congo

NCT02741024 | Completed Phase 4

• 1 other identifier: MSansFrontieres
• Study Type: interventional
• Target: 288
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Percentage of children with adequate parasitological clearance after treatment of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL)

  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).

  42 days

Secondary Outcomes (2)

• 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

Study Arms (2)

Amodiaquine-Artesunate (ASAQ)

ACTIVE COMPARATOR

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)

Drug: Amodiaquine-Artesunate (ASAQ)

Artemether-Lumefantrine (AL)

ACTIVE COMPARATOR

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).

Drug: Artemether-Lumefantrine (AL)

Interventions

Amodiaquine-Artesunate (ASAQ) DRUG

Treatment on site with Amodiaquine-Artesunate according to the manufacturer's dose and instruction and follow-up for a period of 42 days. Drugs will be given under direct supervision, either at the clinic or at home

Also known as: coarsucam

Amodiaquine-Artesunate (ASAQ)

Artemether-Lumefantrine (AL) DRUG

Treatment on site with Artemether-lumefantrine combination according to the manufacturer's dose and instruction and follow-up for a period of 42 days.

Also known as: coartem

Artemether-Lumefantrine (AL)

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• History of hypersensitivity reactions or contra-indications to any medicines being tested.

Sponsors & Collaborators

• Medecins Sans Frontieres, Netherlands: lead

Related Publications (1)

• de Wit M, Funk AL, Moussally K, Nkuba DA, Siddiqui R, Bil K, Piriou E, Bart A, Bahizi Bizoza P, Bousema T. In vivo efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria: an open-randomized, non-inferiority clinical trial in South Kivu, Democratic Republic of Congo. Malar J. 2016 Sep 6;15(1):455. doi: 10.1186/s12936-016-1444-x.

  PMID: 27599612 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

amodiaquine, artesunate drug combination; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Marit de Wit, MD, MIH

  Medecins sans Frontieres, Operational Centre Amsterdam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Health Advisor

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: April 18, 2016
• Study Start: October 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 18, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share