Test Efficacy Study on the Recommended Antimalarial Drugs in the Democratic Republic of the Congo (TES2022)

Efficacy and Safety of Artesunate-amodiaquine and Artemether-lumefantrine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Democratic Republic of the Congo: a Randomized Controlled Trial (TES2022)

Malaria remains a public health concern, despite efforts that are invested in the disease control. The Democratic Republic of the Congo (DRC) is one of the most affected countries in Sub Saharan Africa. Artemisinin-based combination treatments (ACTs) are recommended for the treatment of uncomplicated malaria. However, reported cases of mutations that confer to Plasmodium falciparum resistance to artemisinin (the main component of ACTs) constitute a threat to malaria control, particularly in Sub Saharan Africa. Therefore, the recommendation of the World Health Organization to conduct regularly test efficacy studies in endemic countries is paramount.

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

Study Overview

• Status: Completed
• Conditions: Uncomplicated Plasmodium Falciparum Malaria
• Intervention / Treatment: Drug: Artesunate-amodiaquine; Drug: Artemether-lumefantrine

Detailed Description

This is a phase IV, randomized, open label, 2-arm trial. It will be performed in eight malaria sentinel sites around DRC. 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 (including collection of safety data) will be done and malaria testing as well. Dried blood spots will also be prepared whenever microscopy is performed, in order to assess resistance markers and perform the genotyping of the parasite for PCR-adjusted efficacy. Hemoglobin level will be measured on the recruitment day and then every two weeks until day 28.

• Study Type: Interventional
• Enrollment (Actual): 1260
• Phase: Phase 4

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Haut-Katanga
    • Kapolowe, Haut-Katanga, Congo, The Democratic Republic of the
      • Centre de santé Lupidi 1
  • Kasai Central
    • Kazumba, Kasai Central, Congo, The Democratic Republic of the
      • Centres de santé de Mikalayi et Matamba
  • Kongo Central
    • Kimpese, Kongo Central, Congo, The Democratic Republic of the
      • Centre de santé de Coopération
  • Kwilu
    • Vanga, Kwilu, Congo, The Democratic Republic of the
      • Centre de Santé de Vanga
  • Maniema
    • Kalima, Maniema, Congo, The Democratic Republic of the
      • Centre de santé de Kalima
  • Tshopo
    • Kabondo, Tshopo, Congo, The Democratic Republic of the
      • Centres de santé Umoja et Foyer social
  • Tshuapa
    • Boende, Tshuapa, Congo, The Democratic Republic of the
      • Centre de santé Boende 2 Nsele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 a guardian
• living within the study catchment area
• absence of severe manutrition
• absence of infectious diseases that can be responsible of fever
• absence of allergy to the study drugs

Exclusion Criteria:

• presence of general danger signs 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;
• body weight below 5 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Artesunate-amodiaquine; tablets of ASAQ Winthrop®	Drug: Artesunate-amodiaquine; Tablets; Other Names: ASAQ Winthrop®
Experimental: Artemether-lumefantrine; tablets of Coartem Dispersible®	Drug: Artemether-lumefantrine; Tablets; Other Names: Coartem Dispersible®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR adjusted efficacy	Absence of fever and negative blood smear during the follow-up until day 28 or new infection occurred during the follow-up.	day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of adverse events and serious adverse events	Number of adverse events and serious adverse events that every participant will experience	day 28
Prevalence of HRP2 deletion	Proportion of positive samples that fail to be detected by malaria rapid diagnostic tests due to the deletion of the related antigen	Baseline
Prevalence of resistance markers at baseline	Proportion of samples containing different markers of resistance to different antimalarial drugs	Baseline
Quantification of Lumefantrine	Level of lumefantrine in the blood of children who will be randomized to the Artemether-lumefantrine arm	day 7

Collaborators and Investigators

• Sponsor: Ministry of Public Health, Democratic Republic of the Congo
• Collaborators: Centers for Disease Control and Prevention; Global Fund

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Actual): September 24, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: September 24, 2023
• First Submitted That Met QC Criteria: October 7, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; Artemether-lumefantrine; Uncomplicated malaria; Artesunate-amodiaquine; Artemisinin-based Combination Treatment
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Lumefantrine; Artemether; Artesunate; Artemether, Lumefantrine Drug Combination; Amodiaquine
• Other Study ID Numbers: ASAQ-AL 2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No