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.: PACTR202405571736678 Date of Registration: 31/05/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A pragmatic study to assess the efficacy/effectiveness, safety and tolerability of a single day artesunate-pyronaridine plus sulfadoxine-pyrimethamine for the treatment of uncomplicated malaria in adults and children.
Official scientific title A pragmatic study to assess the efficacy/effectiveness, safety and tolerability of a single day artesunate-pyronaridine plus sulfadoxine-pyrimethamine for the treatment of uncomplicated malaria in adults and children.
Brief summary describing the background and objectives of the trial There is an identified need for antimalarial medicines that are simpler and easier to take, such as a single-dose cure (Alonso et al., 2011). Not only would such a medicine facilitate “directly observed therapy”, which would help to prevent the emergence of drug resistance, it would also reduce the cost of treatment (Mischlinger et al., 2016). One of the defined ultimate goal for the development of next-generation antimalarial drugs is to develop a combination of new compounds that block all the stages and are potent enough to work as a curative single-dose, described as a Single Exposure, Radical Cure and Prophylaxis (SERCaP) treatment. This combination will also have to be affordable to the population in need of these drugs (Burrows et al., 2017, 2013; Drugs, 2011). However, a single dose cure can also be considered a pharmacological challenge as the administered dose needs to be excessively high to achieve curative plasma drug concentrations over a sufficient time, accounting for inter-individual differences in bioavailability, ensuring clearance of parasites in patients without significant semi-immunity, such as children, without posing any relevant safety concerns (Mbassi et al., 2023). Combining the current standard antimalarial treatments substantially reduces treatment failure, recrudescence and gametocyte carriage, preventing the emergence and spread of drug resistance and interrupting the transmission of P. falciparum. Coupled with early detection and confirmed diagnosis, this strategy represents one way forward in the chemotherapy of malaria. The triple-ACT strategy is expected to maximise the possibility of a transition to next-generation antimalarials currently under development. The main objectives of the study are to assess the efficacy/effectiveness, safety and tolerability of single day AP plus SP particularly in children younger than 10 years Primary: To compare the effectiveness of 1-day AP plus SP versus 3-day AL in treating uncomplicated m
Type of trial RCT
Acronym (If the trial has an acronym then please provide) 1DCURE
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 21/05/2024
Actual trial start date
Anticipated date of last follow up 31/12/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 1000
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 Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group AP plus SP Single dose single day Patients in the intervention arm will be given AP plus SP under direct observation. Fixed-dose artesunate-pyronaridine (Pyramax® Shin Poong Pharmaceutical, Seoul, South Korea) will be administered once for a single day with two formulations to facilitate the dosing in young infants, children and adults. The dose will be based on patient body weight. Two strengths and formulations of Pyramax will be provided to facilitate the dosing in adults, children, and young infants: • Tablets of 180:60 mg of pyronaridine and artesunate (patients ≥20kg), • Granules of 60:20 mg of pyronaridine and artesunate (patients 5-19kg). Fixed-dose sulfadoxine-pyrimethamine (500:75mg) tablets will be given orally once, according to bodyweight. 25mg/kg sulfadoxine and 1.25mg/kg pyrimethamine as single dose. 500
Control Group Artemether lumefantrine Twice daily for 3 days 3 days Control arm: Fixed-dose artemether-lumefantrine (20:120mg and 80:480mg) tablets will be given orally, twice daily. The patients will be instructed to take one AL dose every 12 hours over a period of three days, i.e. at Day 0 (initial dose at hour 0 and then after 8 hours), then at Day 1 (after 24 hours and 36 hours) and after on Day 2 (after 48 hours and then after 60 hours). Only the first dose will be administered under supervision in the clinic, the subsequent doses will be taken by the subject at home. 500 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations: o Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children. o Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear)). • Weight ≥5 kg. • Ability to take an oral medication. • Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old), or on verbal consent given in front of a witness signing the informed consent, and access to health facility. The patient has to comply with all scheduled follow-up visits. • Patients with clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4). • Known allergy to any of the study drugs. • Known pregnancy. • Lactating women should be excluded if other anti-malarial treatments are available. • Complicated malaria as per WHO 2012 definition (Annex 2). • Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study. 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: 1 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 6 Month(s) 100 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 17/05/2024 CEI CERMEL
Ethics Committee Address
Street address City Postal code Country
Route Abongo Lambarene 0242 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR) [intention to treat and per-protocol populations] 28 days
Secondary Outcome Main secondary evaluation criterion: Incidence of adverse events including serious adverse events and adverse events of special interest; All time points
Secondary Outcome Crude Day 28 cure rate by species and PCR adjusted cure rate for Day 28 cure rate for P. falciparum [intention to treat and per-protocol population] day 28
Secondary Outcome Recurrence, reinfection and recrudescence rate until day 28 Day 7 and day 28
Secondary Outcome Gametocyte carriage up to day 28 by microscopy. day 7 and day 28
Secondary Outcome Time between malaria episodes and frequency of repeat episodes before and after Day 28 All
Secondary Outcome Compliance of AL will be assessed by counting the number of tablets dispensed but not taken, when the CHW visits the patient at home Day 7
Secondary Outcome Safety (including hepatic safety) in retreated patients. Subsequent malaria episodes
Secondary Outcome Haematology recovery, that is, haemoglobin changes between day 0 and day 28. Day 0 and day 28
Secondary Outcome Time between malaria episodes and frequency of repeat episodes before and after Day 28 All
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de Recherches Medicales de Lambarene Route Abongo Lambarene 0242 Gabon
Four Place satellite site Massanga Four Place Gabon
Sindara satellite site ISSA Sindara Gabon
Mighoma satellite site Mougoutsi Tchibanga Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
CERMEL Route Abongo Lambarene 0242 Gabon
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor CERMEL Route Abongo Lambarene 0242 Gabon Research Centre
COLLABORATORS
Name Street address City Postal code Country
Michael Ramharter Bernhard-nocht-strasse 74 Hamburg 20359 Germany
Peter Kremsner Wilhelmstrasse 27 Tuebingen 72074 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ghyslain Mombo Ngoma ghyslain.mombongoma@cermel.org +24177092785 Route Abongo
City Postal code Country Position/Affiliation
Lambarene 0242 Gabon Head of Clinical Operations
Role Name Email Phone Street address
Public Enquiries Ghyslain Mombo Ngoma ghyslain.mombongoma@cermel.org +24177092785 Route Abongo
City Postal code Country Position/Affiliation
Lambarene 0242 Gabon Head of Clinical Operations
Role Name Email Phone Street address
Scientific Enquiries Peter Kremsner peter.kremsner@uni-tuebingen.de +49070712982365 Wilhelmstrasse 27
City Postal code Country Position/Affiliation
Tuebingen Germany Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared with Researchers who provide a methodologically sound proposal for any purpose by signing a data access agreement Informed Consent Form,Study Protocol Immediately after publication Provide a methodologically sound proposal Any purpose Sign a data access agreement
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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