Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202201797112873 Date of Approval: 06/01/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Antimalrials tri-therapy with atovaquone-proguanil for treatment of uncomplicated malaria in African children
Official scientific title A multicentre phase III non-inferiority trial to evaluate safety, tolerability and efficacy of artemether+lumefantrine + atovaquone-proguanil tri-therapy versus artemether+lumefantrine bi-therapy for the treatment of uncomplicated malaria in African children aged 6 to 10 years.
Brief summary describing the background and objectives of the trial The overall aim of this phase III clinical trial (main study = study II) is to develop a readily deployable highly efficacious, safe and well tolerated antimalarial triple combination therapy for young children. This is achieved by evaluating the efficacy, safety and tolerability of artemether-lumefantrine (AL) + atovaquone-proguanil (AP) tri-therapy (AL+AP) compared to standard AL therapy (+placebo) for the treatment of uncomplicated Plasmodium falciparum malaria in African children aged 6 months to 10 years.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ASAAP Main
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 17/10/2021
Actual trial start date 07/01/2022
Anticipated date of last follow up 29/02/2024
Actual Last follow-up date 30/03/2024
Anticipated target sample size (number of participants) 1664
Actual target sample size (number of participants) 1664
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group artemether lumefantrine and atovaquone proguanil artemether-lumefantrine twice daily + atovaquone-proguanil, twice daily 3 consecutive days Artemether-lumefantrine is an approved drug combination, can be found on the WHO list of essential medicines, and it is registered in the country where the trial will take place. Atovaquone-proguanil is an approved drug combination but is not registered in the country where the trial will take place. 832
Control Group artemether lumefantrine and placebo artemether-lumefantrine twice daily placebo twice daily over 3 consecutive days Artemether-lumefantrine is an approved drug combination, can be found on the WHO list of essential medicines, and it is registered in the country where the trial will take place. Placebo: P-Dragees rosa Lichtenstein, Artesan Pharma GmbH & Co. KG, approval number (Germany): 6927257.00.00 832 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Children in the age of 6 to 59 months 2. Body weight ≥5.0kg 3. Fever (≥37.5°C axillary or 38.0°C oral, rectal or tympanic body temperature) or history of fever in the preceding 24 hours 4. Uncomplicated P. falciparum mono-infection with equal or more than 1,000 and less than 200,000 asexual P. falciparum parasites per microliter of blood. 5. Signed written informed consent from the child’s legal representative 6. Ability to comply with study procedures and follow-up schedules 7. Willing to stay in study area during the period of follow-up 8. Ability to take oral medication 1. Presence of severe malaria following WHO definition (see Annex 2: WHO definitions for severe falciparum malaria and danger signs) 2. Reported intake of any antimalarial drug within the previous 28 days 3. Intake of drugs with antimalarial activity or contraindicated drugs within the previous 28 days 4. Administration of strong inducers or inhibitors of CYP3A4 such as rifampin, carbamazepine, phenytoin, millepertuis/St. John’s wort/ hypericum perforatum, grapefruit within the previous 28 days 5. Known history or evidence of clinically significant medical disorders as determined by the investigator 6. Severe malnutrition assessed by middle upper arm circumference (< 115 mm) according to WHO standard 7. Screening hemoglobin level <7 g/dL 8. Known hypersensitivity or contraindications to any AL and/or AP components 9. Known QT prolongation 10. Previous participation in a malaria vaccine study 11. Participation in the ASAAP study during the previous 42 days 12. Participation in other interventional studies within the previous 28 days 13. Patients that the investigator considers would be at particular risk if participating in the study Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 59 Month(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 11/08/2021 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Adabraka Polyclinic Accra MB 190 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/10/2021 Comite National d Ethique pour la Recherche en Sante
Ethics Committee Address
Street address City Postal code Country
Akpapka COTONOU BP 01 882 Benin
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/08/2021 Comite dEthique de l USTTB
Ethics Committee Address
Street address City Postal code Country
Point-G Bamako 1805 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 05/10/2021 Comite National d Ethique de la Recherche au Gabon
Ethics Committee Address
Street address City Postal code Country
xxx Libreville 2217 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Day-28 efficacy of AL+AP and AL+placebo for the treatment of uncomplicated P. falciparum malaria in African children aged 6 to 59 months defined as PCR-adjusted adequate clinical and parasitological response (ACPR) excluding reinfections, in the per-protocol (PP) population. Day 28
Primary Outcome Day-28 efficacy of AL+AP and AL+placebo for the treatment of uncomplicated P. falciparum malaria in African children aged 6 to 59 months defined as PCR-adjusted adequate clinical and parasitological response (ACPR) excluding reinfections, in the modified intention-to-treat (mITT) population. Day 28
Secondary Outcome to assess PCR-unadjusted day-28 ACPR by treatment arm in both the PP and the mITT population; Day 28
Secondary Outcome to assess PCR- adjusted and unadjusted day-42 ACPR by treatment arm in both the PP and in the mITT population; Day 42
Secondary Outcome to assess cure rate at days 14, 21, 28, 35 and 42 by treatment arm to evaluate post-treatment prophylactic efficacy in both PP and mITT populations; days 14, 21, 28, 35 and 42
Secondary Outcome to assess types, proportion, severity and causality of adverse events (AEs) during treatment follow-up by treatment arm as measures of tolerability and safety; continuously during the conduct of the study
Secondary Outcome to assess day-7 lumefantrine and desbutyl-lumefantrine plasma concentrations by treatment arm; Day 7
Secondary Outcome to estimate day-7 atovaquone, proguanil and its metabolite (cycloguanil) plasma concentrations when the treatment is AL +AP Day 7
Secondary Outcome to assess day 3 positivity rate by treatment arm in both PP and mITT; day 3 positivity rate is defined as the proportion of patients who were still parasitaemic on day 3 after initiation of treatment Day 3
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
St. Francis Xavier Hospital Cape Coast Road Assin Foso Ghana
Centre de Recherches Medicale de Lambarene BP 242 Lambarene Gabon
Public Health Centre of Dodji Bata xxxxx Allada Benin
Health Centre of Faladje xxxxx Faladje Kati Mali
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership Anna van Saksenlaan 51 HW The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kwame Nkrumah University of Science and Technology PMB UPO Kumasi Ghana University
COLLABORATORS
Name Street address City Postal code Country
Universite Paris Descartes MERIT UMR 261 4, Avenue de l Observatoire Paris 75006 France
Bernhard Nocht Institute for Tropical Medicine Bernhard Nocht Strasse 74 Hamburg 20359 Germany
Centre de Recherches Medicale de Lambarene BP 242 Lambarene Gabon
Institut de Recherche Clinique du Benin 01 BP 1114 Abdomey Calavi Benin
Kumasi Centre for Collaborative Research in Tropical Medicine PMB, UPO Kumasi Ghana
Malaria Research and Training Centre BP 1805 Bamako Mali
IRD Campus Lavalette UMR 224 MIVEGEC 911 avenue Agropolis Montpellier France
Institut des Science et Techniques de Bobo 01 BP 2779 Bobo Dioulasso Burkina Faso
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Oumou Maiga Ascofare maiga@kccr.de +233322060351 xxxx
City Postal code Country Position/Affiliation
Kumasi Ghana KCCR KNUST
Role Name Email Phone Street address
Scientific Enquiries Jerome Clain jerome.clain@parisdescartes.fr +33153739657 4 avenue de l Observatoire
City Postal code Country Position/Affiliation
Paris 75006 France University Paris Descartes
Role Name Email Phone Street address
Public Enquiries John Amuasi amuasi@kccr.de +233322060351 PMB, UPO
City Postal code Country Position/Affiliation
Kumasi Ghana KCCR KNUST
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes In line with the funding conditions, IPD is to be shared. However, this will be de-identified IPD that used to generate the results reported (text, tables, figures and appendices). IPD sharing will begin after publication of primary results and will be available for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. The IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The below mentioned URL will carry information on how to access the IPD at the end of the study and addresses that contain additional information about the plan to share IPD. This will include the repository in which the IPD will be deposited. The website shall also explain the eligibility criteria and internal review processes for reviewing data requests. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol From the time of publication and for a period which is aligned with the data sharing agreements approved by the research ethics committees of the counties/sites participating in the trial. This IPD shall be made available via a request and evaluation process to investigators whose proposed research has received IRB approval. All investigators to whom this IPD is made available will be required to be part of the execution of a data use agreement. The data shall be made available through a governed data access process which includes a transparent, accountability and decision-making process: Completion of data request form Evaluation by a data access committee Data sharing Agreement Secure transfer of data
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://asaap-malaria.org/ No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information