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

• ClinicalTrials.gov Identifier: NCT04618523
• Recruitment Status: Completed
• First Posted: November 6, 2020
• Last Update Posted: February 9, 2022
• Sponsor: Ministry of Public Health, Democratic Republic of the Congo
• Collaborators: University of Kinshasa; World Health Organization; Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
• Information provided by (Responsible Party): Prof. Gauthier Mesia Kahunu, Ministry of Public Health, Democratic Republic of the Congo

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malaria	Drug: Artesunate-amodiaquine; Drug: Artemether-lumefantrine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 26, 2020
• Actual Primary Completion Date: February 8, 2022
• Actual Study Completion Date: February 8, 2022

Arms and Interventions

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 Name: 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 Name: Coartem dispersible®

Outcome Measures

Primary Outcome Measures :

1. PCR adjusted efficacy [ Time Frame: 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 :

1. Proportion of adverse events and serious adverse events [ Time Frame: 28 days ]
   Number of adverse events and serious adverse events that every participant will experience
2. Proportion of participants with positive blood smear at day 3 [ Time Frame: 3 days ]
   Number of participants who will still have parasites on day 3

Other Outcome Measures:

1. Presence of Plasmodium falciparum resistance markers and deletion of HRP2 [ Time Frame: 28 days ]
   Resistance markers and deletion of HRP2 will be assessed

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 59 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Congo, The Democratic Republic of the

Centre de Santé Lupidi 1

Kapolowe, Haut-Katanga, Congo, The Democratic Republic of the

Centre de Santé de Référence Mikalayi

Kazumba, Kasai-central, Congo, The Democratic Republic of the

Centre Evangélique de Coopération

Kimpese, Kongo 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

Sponsors and Collaborators

Ministry of Public Health, Democratic Republic of the Congo

University of Kinshasa

World Health Organization

Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo

Investigators

• Principal Investigator: Gauthier Mesia Kahunu, PhD; Université de Kinshasa

More Information

• Responsible Party: Prof. Gauthier Mesia Kahunu, Professor, Ministry of Public Health, Democratic Republic of the Congo
• ClinicalTrials.gov Identifier: NCT04618523
• Other Study ID Numbers: ASAQ-LA 2019 DRC
• First Posted: November 6, 2020
• Last Update Posted: February 9, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Artesunate; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination; Amodiaquine; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Schistosomicides; Antiplatyhelmintic Agents; Anthelmintics