NCT04778813

Evaluation of Three Artemisinin-based Combinations for the Treatment of Uncomplicated Malaria in Childreen in Burkina Faso (CHIMIO2)

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1,050 (estimated)
• Sponsor: Centre national de recherche et de formation sur le paludisme · Other Government
• Sex: All
• Age: 6 Months – 12 Years
• Healthy volunteers: Not accepted

Summary

Bakground In Burkina Faso, since the adoption of this new malaria treatment policy in 2005, several studies evaluating the efficacy and tolerance of ACTs have been carried out by different research teams at different sites according to an irregular chronology and according to different methods. Studies conducted in children 6 to 59 months with supervised use of ACTs indicate adequate clinical and parasitological response rates varying between 93% to 98% after correction to the PCR at day 28. With the introduction of seasonal malaria chemoprevention (SMC) by the Sulfadoxine-Pyriméthamime/amodiaquine combination in almost all health districts of Burkina Faso, ASAQ is no longer recommended for the treatment of uncomplicated malaria in the areas covered by this intervention. In 2017, DHA-PPQ was added to the national treatment guidelines as a first-line treatment option. The therapeutic efficacy study carried out in 2017-2018 by the CNRFP showed a PCR-corrected treatment failure rate of over 10% with the AL combination. However, molecular analyzes have not shown the presence of mutations at position 580 on the PfK-13 gene which is associated with resistance to artemisinin derivatives. The combination artesunate-pyronaridine (As-Pyr) was recently added to the WHO Prequalified Medicines List and Essential Medicines List. In 2019, it received regulatory marketing authorization to be used as a treatment for malaria in Burkina Faso. Burkina Faso (along with the Niangoloko and Bobo Dioulasso centers) was one of the countries where clinical trials p ar the As-Pyr association were led. This combination has been found to be effective and well tolerated in Burkina Faso. The combinations of AL and DHA-PPQ were observed to be well tolerated in previous efficacy studies. The combinations DHA-PPQ and As-Pyr could potentially replace AL as first-line treatment in Burkina Faso if the results of these planned therapeutic efficacy studies continue to show a high rate of failures with AL. The herein study aims to assess the efficacy and safety of AL, DHA-PPQ and As-Pyr in the treatment of uncomplicated malaria in children in three health districts in Burkina Faso, namely the health districts of Banfora, Nanoro and de Gourcy. This study will provide PNLP and the Ministry of Health with additional data and evidence on the safety and efficacy of these treatments against malaria in Burkina Faso. Primary objective The primary objective is to assess the clinical and parasitological efficacy of AL, DHA-PPQ and AS-Pyr in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 12 years, corrected by PCR on day 28 (AL) or 42 (DHA-PPQ \& AS-Pyr). Study settings The study will be conducted at the medical center (CMA of Niangoloko, the Clinical Research Unit of Nanoro (URCN) and the medical center with surgical antenna (CMA) of Gourcy. Populations Febrile patients of both sexes aged between 6 months and 12 years with confirmed uncomplicated P. falciparum mono-infestation who wellcome for an outpatient visit to the health facilities. Procedures It will be a multicenter, randomized, open-label, three-arm study involving three sites representing the three epidemiological facies of malaria in Burkina Faso. The three therapeutic combinations (AL, DHA-PPQ and As-Pyr) will be tested in different sites with different characteristics of transmission and resistance of malaria. Children with uncomplicated malaria who meet the criteria for inclusion in the study will be recruited and treated with the combination of AL or DHA-PPQ or As-Pyr. They will be monitored for 28 days for the AL group and 42 days for the DHA-PPQ and AS-Pyr arm. The follow-up will consist of scheduled control visits during which clinical examinations and laboratory tests will be carried out. A total of 1050 children will be enrolled in the study. Main results 1. The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or adequate clinical and parasitological response. 2. The frequency and nature of adverse events. 3. The blood concentration of lumefantrine on day 7

Conditions

• Malaria
• Burkina Faso

Interventions

Type	Name	Description
DRUG	Artemether-lumefantrine	In each study site, children fulfilling the inclusion criteria will be assigned randomly to one of three treatment groups: AL, DHA-PPQ or As-Pyr group. Sealed envelopes each containing no more than 10 other small envelopes with randomization numbers and treatment will also be provided. These will be used over time, respecting the ascending order of the numbers to randomly distribute the eligible children after selection in each of the three treatment groups. The treatment to be administered will not be known until after the randomization process. The drugs will be administered based on weight according to the instructions from the drug manufacturer. AL will be administered with fatty food or milk according to the manufacturer's recommendations. All doses of the drug will be administered under the direct supervision of a qualified team member designated by the principal investigator.

Timeline

• Start date: 2021-06-01
• Primary completion: 2021-12-31
• Completion: 2022-06-01
• First posted: 2021-03-03
• Last updated: 2021-03-03

Locations

1 site across 1 country: Burkina Faso