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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202104845356660 Date of Registration: 15/04/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Developing Triple Artemisinin Combination Therapies Trial in Africa
Official scientific title A multi-centre randomised controlled non-inferiority trial to compare the efficacy, safety and tolerability of Triple Artemisinin-based Combination Therapies versus first-line ACTs + placebo for the treatment of uncomplicated Plasmodium falciparum malaria in Africa
Brief summary describing the background and objectives of the trial Artemisinin and partner drug resistance have resulted in high failure rates of artemisinin-based combination therapies (ACTs) in the GMS. Spread or emergence of resistance beyond the GMS are threats to malaria control. Triple ACTs (TACTs), combining an artemisinin and two existing partner drugs, could be a stop-gap therapy for treating multidrug-resistant malaria until new antimalarials are available. Where resistance is not established, deployment of TACTs could delay or prevent emergence of resistance and could prolong the longevity of antimalarial compounds used in any triple-drug combination. The DeTACT-Africa Trial is a large scale randomized clinical trial in 8 African countries to compare the efficacy, safety and tolerability of the TACTs artemether-lumefantrine + amodiaquine and artesunate-mefloquine+piperaquine and the standard ACTs artemether-lumefantrine + placebo and artesunate-mefloquine + placebo.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) DeTACT Africa
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 01/09/2020
Actual trial start date 01/09/2020
Anticipated date of last follow up 31/12/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 3240
Actual target sample size (number of participants)
Recruitment status Recruiting
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 Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Artemether Lumefantrine Total daily dose approximately matches the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg. Placebo tablets for amodiaquine administered to this control group are identical in size, shape and color to the amodiaquine tablets. 2 doses per day for 3 days Control for Artemether-lumefantrine + amodiaquine (AL-AQ) Triple combination 72 Active-Treatment of Control Group
Control Group Artesunate Mefloquine Total daily dose approximately matches the WHO-recommended target ranges of artesunate 4 mg/kg/day and mefloquine 8.3 mg/kg/day. Placebo tablets for piperaquine administered to this control group are identical in size, shape and color to the piperaquine tablets. 1 dose per day for 3 days Control for artesunate-mefloquine + piperaquine (ASMQ+PPQ) Triple combination This arm and the matching experimental arm (ASMQ+PPQ) will not be implemented in Rwanda only. 72 Active-Treatment of Control Group
Experimental Group Artemether Lumefantrine Amodiaquine Total daily dose approximately matches the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg. Target total daily dose for amodiaquine is 10 mg (4.5-15mg)/kg/day. 2 doses per day for 3 days Experimental arm with triple drug combination (AL-AQ) 144
Experimental Group Artesunate Mefloquine Piperaquine Total daily dose approximately matches the WHO-recommended target of artesunate 4 mg/kg/day and mefloquine 8.3 mg/kg/day. Target total daily dose for piperaquine is 24 mg/kg/day in patients <25 kg (range 16.0 - 32.0 mg/ kg) and 18 mg/kg/day in patients >= 25 kg (range 15.0 - 29.4 mg/kg). 1 dose per day for 3 days Experimental arm with Artesunate-Mefloquine + Piperaquine (ASMQ-PPQ) Triple combination. This arm and the matching control arm (ASMQ) will not be implemented in Rwanda only. 144
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Male or female, aged ≥6 months to <12 years (For Gambia, Rwanda sites only: ≥6 months) • Ability to take oral medication • Acute uncomplicated P. falciparum monoinfection • Asexual P. falciparum parasitaemia: 1,000/µL to ≤10% parasitaemia, determined on a peripheral blood film (At Gambia, Rwanda sites only: For subjects ≥12 years – 1000/µL to 200,000/µL) • Fever defined as ≥ 37.5°C tympanic temperature or a history of fever within the last 24 hours • Written informed consent by the subject or by the parent/guardian in case of children lower than the age of consent and assent if required (per local regulations) • Willingness and ability of the subjects or parents/guardians to comply with the study protocol for the duration of the study Signs of severe malaria (adapted from WHO criteria) Patients not fulfilling criteria for severe malaria but with another indication for parenteral antimalarial treatment at the discretion of the treating physician Haematocrit <15% at screening (For Gambia, Rwanda sites only: For subjects ≥12 years – Haematocrit <20% at screening) Subjects who have received artemisinin or a derivative within the previous 7 days OR lumefantrine or amodiaquine within the previous 14 days OR mefloquine or piperaquine within the previous 30 days In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within the last 14 days. Acute illness other than malaria requiring systemic treatment; Severe acute malnutrition (in Niger only – only those patients with Severe Acute Malnutrition and complications requiring inpatient nutritional treatment will be excluded) Known HIV infection Known tuberculosis infection For females: post-menarche (For Gambia, Rwanda sites only: females who are pregnant, trying to get pregnant or are lactating) History of allergy or known contraindication to any of the study drugs, including neuropsychiatric disorders and epilepsy Previous splenectomy Enrolment in DeTACT in the previous 3 months Participation in another interventional study in the previous 3 months 80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 6 Month(s) 99 Year(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
Yes 25/04/2019 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Research Services, University Offices, Wellington Square Oxford OX1 2JD United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 42-day efficacy defined as PCR-corrected adequate clinical and parasitological response (ACPR). Day 42
Secondary Outcome For safety and tolerability: Incidence of adverse events and serious adverse events within the first 42 days including markers of hepatic, renal or bone marrow toxicity; cardiotoxicity, in particular QT or QTc-interval above 500 ms at timepoint H4 and H52/H64 and between these time points; change in haemoglobin concentration at day 3, 7, 28, stratified for G6PD status/genotype; proportion of subjects requiring retreatment due to vomiting within 1 hour after administration of the study drugs; proportion of subjects that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study because of drug related serious adverse event Day 42
Secondary Outcome For efficacy: 63-day PCR corrected and uncorrected efficacy; 42-day PCR uncorrected efficacy; parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance; proportion of subjects with microscopically detectable P. falciparum parasitaemia at Day 3; fever clearance time (i.e. the time taken for the tympanic temperature to fall below 37.5 ºC in patients who were febrile at inclusion); proportion of subjects with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment. Day 42, Day 63
Secondary Outcome For PK/PD interactions: Pharmacokinetic profiles and interactions (including Cmax and AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated subjects in correlation with pharmacodynamics measures of drug efficacy; day 7 plasma levels of partner drugs in correlation with treatment efficacy and treatment arm Up to Day 7
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Institut des Sciences et Techniques Avenue de Sya Porte 540 Bobo Dioulasso Burkina Faso
MRC Unit The Gambia at LSHTM Atlantic Boulevard, Fajara, P. O. Box 273 Banjul Gambia
Centre National de Formation en Recherche et Sante Rurale de Meferinyah B.P. 2649 Conakry Guinea
Epicentre Niger Quartier Plateau Boulevard Mali Bero Issa Beri Rue 31 Porte 93 BP 13 330 Niamey Niger
Centre for Malaria and Other Tropical Diseases University of Ilorin Teaching Hospital, PMB 1459, Old Jebba Rd, Oke-Ose, Ilorin Kwara State Nigeria
Kinshasa School of Public Health BP 11850 Kin I School of Medicine, University of Kinshasa Kinshasa Democratic Republic of the Congo
College of Medicine and Health Sciences University of Rwanda University of Rwanda Kigali Rwanda
National Institute of Medical Research Tanga Medical Research Centre Hospital Rd Tanga Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
Foreign and Commonwealth Development Office King Charles Street London SW1A 2AH United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Research Services, University Offices Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Arjen Dondorp Arjen@tropmedres.ac +6622036333 420/6 Ratchawithi Road, Ratchathewi
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Deputy Director Mahidol Oxford Tropical Medicine Research Unit
Role Name Email Phone Street address
Public Enquiries Mehul Dhorda Mehul@tropmedres.ac +6622036333 420/6 Ratchawithi Road, Ratchathewi
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Project Coordinator
Role Name Email Phone Street address
Scientific Enquiries Mehul Dhorda Mehul@tropmedres.ac +6622036333 420/6 Ratchawithi Road, Ratchathewi,
City Postal code Country Position/Affiliation
Bangkok 10400 Thailand Project Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes With participant’s consent, participant’s data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with data repositories such as the WorldWide Antimalarial Resistance Network (WWARN, terms of submission here: http://www.wwarn.org/tools-resources/terms-submission) or other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records, through interviews, or from mapping data. Clinical Study Report,Informed Consent Form,Study Protocol After completion of trial activities and reporting Access to data will be through an application to the Mahidol Oxford Tropical Medicine Research Unit Data Access Committee (MORU-DAC). Applicants will be asked to complete an Application Form and a Data Access agreement. Applications are considered by the DAC on a case-by-case basis informed by an assessment criteria, defined in the DAC terms of reference. The type of agreement that applicants are asked to complete will be determined by the DAC. Consideration will involve consultation with PIs, relevant collaborators and other experts. Additional specific conditions of access may be implemented including collaboration and cost-recovery for preparation of datasets. Additional information here: MORU Data Sharing Policy https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing, WWARN Terms of Data Access https://www.wwarn.org/tools-resources/terms-data-access
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing 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