Safety and Efficacy of Recommended Antimalarial in the Democratic Republic of the Congo

Phase 4

Completed

• Conditions: Malaria
• Interventions: Drug: Artemether-lumefantrine; Drug: Artesunate-amodiaquine

• Registration Number: NCT04618523
• Lead Sponsor: Ministry of Public Health, Democratic Republic of the Congo

Brief Summary

Despite all efforts, malaria remains a public health concern, in particular in the Democratic Republic of the Congo (DRC). The National Malaria Control program recommends artemisinin-based combination treatments (ACTs), in particular artesunate-amodiaquine or artemether-lumefrantrine for the treatment of uncomplicated malaria. Previous studies indicated that ACTs are still effective, with efficacy above the required threshold of 90%. It is required to assess regularly the efficacy of antimalarial drugs. I In case of increasing failure rates, alternative options can be decided ontime.

The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®) and artemether-lumefantrine (Coartem Dispersible®) at day 28 in the treatment of uncomplicated Plasmodium falciparum malaria in six surveillance sites around DRC.

Detailed Description

This is a phase IV, randomized, open label, 2-arm trial. It will be performed in six malaria sentinel site around the Democratic Republic of the Congo. Children aged 6 to 59 months with confirmed Plasmodium falciparum uncomplicated malaria will be enrolled after informed consent granted by a parent or guardian. They will be randomized to receive either artesunate-amodiaquine or artemether lumefrantrine during 3 days (directly observed treatment) and then followed up until day 28. At each visit, clinical examination will be done and malaria testing as well. Hemoglobin level will be measured on recruitment day and then every two weeks until day 28.

Study Timeline

• Study First Submitted: 2020-10-22
• Study Start: 2020-10-26
• Study First Submitted QC: 2020-10-31
• Study First Posted: 2020-11-06
• Status Verified: 2022-02
• Primary Completion: 2022-02-08
• Study Completion: 2022-02-08
• Last Update Submitted: 2022-02-08
• Last Update Posted: 2022-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1117

Inclusion Criteria

• children aged 6 to 59 months
• monoinfection with Plasmodium falciparum with asexual parasite count of 2,000 to 200,000/µL
• axillary temperature ≥ 37.5 °C
• ability to swallow oral medication
• ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule;
• informed consent from a parent or aguardian
• living within the study catchment area

Exclusion Criteria

• presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO;
• body weight < 5kg
• hemoglobin level < 5g/ dL or hematocrit < 15%
• presence of severe malnutrition
• presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• regular medication, which may interfere with antimalarial pharmacokinetics;
• malaria treatment within 2 days prior to recruitment
• history of hypersensitivity reactions or contraindications to any of the medicines being tested or used as alternative treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Artemether-lumefantrine	Artemether-lumefantrine	Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine. Each dose to be taken with high-fat food or drinks (for example milk). One tablet twice daily for children weighing 5 to \<15 kg, two tablets twice daily for those weighing 15 to \<25 kg and three tablets twice daily for those weighing 25 to \< 35 kg, for three days.
Artesunate-amodiaquine	Artesunate-amodiaquine	Tablets containing 25 mg of artesunate and 67.5 mg of amodiaquine: one tablet daily for three days for children weighing 4.5 to 8 kg, and tablets containing 50 mg of artesunate and 135 mg of amodiaquine: one tablet daily for three days for children weighing 9 to 17 kg.

Primary Outcome Measures

Name	Time	Method
PCR adjusted efficacy	28 days	absence of fever and negative blood smear during the follow-up until day 28 and new infections occurred during the follow-up.

Secondary Outcome Measures

Name	Time	Method
Proportion of adverse events and serious adverse events	28 days	Number of adverse events and serious adverse events that every participant will experience
Proportion of participants with positive blood smear at day 3	3 days	Number of participants who will still have parasites on day 3

Trial Locations

Locations (6)

Centre de Santé Lupidi 1; 🇨🇩 Kapolowe, Haut-Katanga, Congo, The Democratic Republic of the

Centre Evangélique de Coopération; 🇨🇩 Kimpese, Kongo Central, Congo, The Democratic Republic of the

Centre de Santé de Référence Mikalayi; 🇨🇩 Kazumba, Kasai-central, Congo, The Democratic Republic of the

Centre de Santé de Référence Rutshuru; 🇨🇩 Rutshuru, Nord-Kivu, Congo, The Democratic Republic of the

Centre de Santé Foyer Social; 🇨🇩 Kisangani, Tshopo, Congo, The Democratic Republic of the

Centre de Santé Boende 2 Nsele; 🇨🇩 Boende, Tshuapa, Congo, The Democratic Republic of the