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

Primary Purpose

Uncomplicated Plasmodium Falciparum Malaria

Status
Recruiting
Phase
Phase 4
Locations
Congo, The Democratic Republic of the
Study Type
Interventional
Intervention
Artesunate-amodiaquine
Artemether-lumefantrine
Sponsored by
Ministry of Public Health, Democratic Republic of the Congo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uncomplicated Plasmodium Falciparum Malaria focused on measuring Uncomplicated malaria, Plasmodium falciparum, Artemisinin-based Combination Treatment, Artemether-lumefantrine, Artesunate-amodiaquine

Eligibility Criteria

6 Months - 59 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre de santé Lupidi 1
  • Centres de santé de Mikalayi et Matamba
  • Centre de santé de Coopération
  • Centre de Santé de VangaRecruiting
  • Centre de santé de KalimaRecruiting
  • Centre Hospitalier Virunga
  • Centres de santé Umoja et Foyer socialRecruiting
  • Centre de santé Boende 2 Nsele

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Artesunate-amodiaquine

Artemether-lumefantrine

Arm Description

tablets of ASAQ Winthrop®

tablets of Coartem Dispersible®

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of adverse events and serious adverse events
Number of adverse events and serious adverse events that every participant will experience
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
Prevalence of resistance markers at baseline
Proportion of samples containing different markers of resistance to different antimalarial drugs
Quantification of Lumefantrine
Level of lumefantrine in the blood of children who will be randomized to the Artemether-lumefantrine arm

Full Information

First Posted
September 24, 2023
Last Updated
October 7, 2023
Sponsor
Ministry of Public Health, Democratic Republic of the Congo
Collaborators
Centers for Disease Control and Prevention, Global Fund
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1. Study Identification

Unique Protocol Identification Number
NCT06076213
Brief Title
Test Efficacy Study on the Recommended Antimalarial Drugs in the Democratic Republic of the Congo
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ministry of Public Health, Democratic Republic of the Congo
Collaborators
Centers for Disease Control and Prevention, Global Fund

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uncomplicated Plasmodium Falciparum Malaria
Keywords
Uncomplicated malaria, Plasmodium falciparum, Artemisinin-based Combination Treatment, Artemether-lumefantrine, Artesunate-amodiaquine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomization 1:1 in two treatment arms: artesunate-amodiaquine and artemether-lumefantrine
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1408 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Artesunate-amodiaquine
Arm Type
Experimental
Arm Description
tablets of ASAQ Winthrop®
Arm Title
Artemether-lumefantrine
Arm Type
Experimental
Arm Description
tablets of Coartem Dispersible®
Intervention Type
Drug
Intervention Name(s)
Artesunate-amodiaquine
Other Intervention Name(s)
ASAQ Winthrop®
Intervention Description
Tablets
Intervention Type
Drug
Intervention Name(s)
Artemether-lumefantrine
Other Intervention Name(s)
Coartem Dispersible®
Intervention Description
Tablets
Primary Outcome Measure Information:
Title
PCR adjusted efficacy
Description
Absence of fever and negative blood smear during the follow-up until day 28 or new infection occurred during the follow-up.
Time Frame
day 28
Secondary Outcome Measure Information:
Title
Proportion of adverse events and serious adverse events
Description
Number of adverse events and serious adverse events that every participant will experience
Time Frame
day 28
Title
Prevalence of HRP2 deletion
Description
Proportion of positive samples that fail to be detected by malaria rapid diagnostic tests due to the deletion of the related antigen
Time Frame
Baseline
Title
Prevalence of resistance markers at baseline
Description
Proportion of samples containing different markers of resistance to different antimalarial drugs
Time Frame
Baseline
Title
Quantification of Lumefantrine
Description
Level of lumefantrine in the blood of children who will be randomized to the Artemether-lumefantrine arm
Time Frame
day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
No
Eligibility 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gauthier Mesia Kahunu, PhD
Phone
+243841209996
Email
mesia.kahunu@unikin.ac.cd
First Name & Middle Initial & Last Name or Official Title & Degree
Hypolite Muhindo Mavoko, PhD
Phone
+243994406532
Email
hypomavoko@gmail.com
Facility Information:
Facility Name
Centre de santé Lupidi 1
City
Kapolowe
State/Province
Haut-Katanga
Country
Congo, The Democratic Republic of the
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guilain Kikunda, MPH
Phone
+243 973 300 136
Email
kikundaghislain@gmail.com
Facility Name
Centres de santé de Mikalayi et Matamba
City
Kazumba
State/Province
Kasai Central
Country
Congo, The Democratic Republic of the
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Papy Mandoko, PhD
Phone
+243 816 575 394
Email
drpmandoko@yahoo.fr
Facility Name
Centre de santé de Coopération
City
Kimpese
State/Province
Kongo Central
Country
Congo, The Democratic Republic of the
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Papy Mandoko, PhD
Phone
+243 816 575 394
Email
drpmandoko@yahoo.fr
Facility Name
Centre de Santé de Vanga
City
Vanga
State/Province
Kwilu
Country
Congo, The Democratic Republic of the
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Mitashi, PhD
Phone
+243 829 233 811
Email
patrick.mitashi@unikin.ac.cd
Facility Name
Centre de santé de Kalima
City
Kalima
State/Province
Maniema
Country
Congo, The Democratic Republic of the
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacques Bianga, MD
Phone
+243810409436
Facility Name
Centre Hospitalier Virunga
City
Goma
State/Province
Nord-Kivu
Country
Congo, The Democratic Republic of the
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Destin Mbongi, PhD
Phone
+243 812 651 218
Email
mbongidestin@gmail.com
Facility Name
Centres de santé Umoja et Foyer social
City
Kabondo
State/Province
Tshopo
Country
Congo, The Democratic Republic of the
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Destin Mbongo, MD
Phone
+243 812 651 218
Email
mbongidestin@gmail.com
Facility Name
Centre de santé Boende 2 Nsele
City
Boende
State/Province
Tshuapa
Country
Congo, The Democratic Republic of the
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Mitashi, PhD
Phone
+243 829 233 811
Email
patrick.mitashi@unikin.ac.cd

12. IPD Sharing Statement

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

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