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

Uncomplicated Plasmodium Falciparum Malaria Clinical Trial

— TES2022  

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 (TES2022)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06076213
• Other study ID #: ASAQ-AL 2022
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: May 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Ministry of Public Health, Democratic Republic of the Congo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1408
• Est. completion date: December 31, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 59 Months

Eligibility

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

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Uncomplicated Plasmodium Falciparum Malaria

Intervention

Drug:
• Artesunate-amodiaquine
Tablets
• Artemether-lumefantrine
Tablets

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Ministry of Public Health, Democratic Republic of the Congo	Centers for Disease Control and Prevention, Global Fund

Country where clinical trial is conducted

Congo, The Democratic Republic of the, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of adverse events and serious adverse events	Number of adverse events and serious adverse events that every participant will experience	day 28
Secondary	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
Secondary	Prevalence of resistance markers at baseline	Proportion of samples containing different markers of resistance to different antimalarial drugs	Baseline
Secondary	Quantification of Lumefantrine	Level of lumefantrine in the blood of children who will be randomized to the Artemether-lumefantrine arm	day 7