Safety and Efficacy of Recommended Antimalarial in the Democratic Republic of the Congo (TET2020)

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

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.

Study Overview

• Status: Completed
• Conditions: 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 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 Type: Interventional
• Enrollment (Actual): 1117
• 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
      • Centre de Santé de Référence Mikalayi
  • Kongo Central
    • Kimpese, Kongo Central, Congo, The Democratic Republic of the
      • Centre Evangélique de Coopération
  • Nord-Kivu
    • Rutshuru, Nord-Kivu, Congo, The Democratic Republic of the
      • Centre de Santé de Référence Rutshuru
  • Tshopo
    • Kisangani, Tshopo, Congo, The Democratic Republic of the
      • Centre de Santé 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: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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 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 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 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.	Drug: Artesunate-amodiaquine; Artemisinin-based combination treatment; Other Names: ASAQ Winthrop®
Experimental: 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.	Drug: Artemether-lumefantrine; Artemisinin-based combination treatment; 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 and new infections occurred during the follow-up.	28 days

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	28 days
Proportion of participants with positive blood smear at day 3	Number of participants who will still have parasites on day 3	3 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Plasmodium falciparum resistance markers and deletion of HRP2	Resistance markers and deletion of HRP2 will be assessed	28 days

Collaborators and Investigators

• Sponsor: Ministry of Public Health, Democratic Republic of the Congo
• Collaborators: World Health Organization; Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo; University of Kinshasa
• Investigators: Principal Investigator: Gauthier Mesia Kahunu, PhD, Université de Kinshasa

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Actual): February 8, 2022
• Study Completion (Actual): February 8, 2022

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 31, 2020
• First Posted (Actual): November 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 8, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Lumefantrine; Artemether; Artesunate; Artemether, Lumefantrine Drug Combination; Amodiaquine
• Other Study ID Numbers: ASAQ-LA 2019 DRC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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