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.: PACTR202607738028407 Date of Registration: 31/07/2026
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Therapeutic Efficacy Study
Official scientific title Open label randomized study to evaluate the in vivo efficacies of Artemether-lumefantrine and Dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in children 6 months to 10 years of age in western Kenya
Brief summary describing the background and objectives of the trial In line with the World Health Organization (WHO) recommendations and standardized protocol, Kenya periodically conducts Therapeutic Efficacy Studies (TES) for the 1st and 2nd line antimalarial medicines to monitor the threat of emergence and spread of parasite resistance to antimalarial drugs. Artemether-lumefantrine (AL) was adopted as first-line antimalarial therapy in Kenya in 2006, and dihydroartemisinin-piperaquine (DHP) as the second-line therapy in 2010. In order to monitor the efficacy and potential development of resistance of Plasmodium falciparum parasites to these two drugs, we will conduct an open-label randomized in-vivo study to monitor the efficacy of these antimalarial therapies. The study design will be a two-arm randomized prospective study at two primary sites located in Kisumu and Kakamega counties of western Kenya: Each site will evaluate the efficacy of AL and DHP. Febrile patients aged between 6 months and 10 years with confirmed uncomplicated Plasmodium falciparum mono infection will be recruited at the two primary health facilities with a high outpatient attendance of malaria patients and followed up for 42 days. At each site, at least 125 study participants will be enrolled per drug (250 patients per site, 500 patients total). Primary clinical and parasitological outcomes will be monitored over a 42-day and 28-day follow-up period to evaluate efficacy of DHP and AL, respectively. The study will determine the proportion of patients with an adequate clinical and parasitological response (ACPR). Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis and capillary electrophoresis. The study will further characterize the polymorphisms of molecular markers of drug resistance and pfHRP2/3 gene deletion. The results from this study will enable the Ministry of Health (MOH) to make timely updates to its malaria treatment and diagnostic policies and add to the global antimalarial drug resistance database.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TES
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 01/12/2026
Actual trial start date
Anticipated date of last follow up 30/06/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 500
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
5440 Kenya Medical Research Institute - Scientific Ethics Review Unit
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 Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Artemether Lumefantrine Weight based, twice in a day 3 days Artemether-Lumefantrine will be administered at a target dose range of 5-24 mg/kg body weight of artemether and 29-144 mg/kg body weight of lumefantrine. Tablets will be administered with fatty food (e.g. a packet of whole milk), twice daily over three days (total, six doses). The first two doses will be given eight hours apart. The correct drug dosage will be determined from the dosing chart. 250 Active-Treatment of Control Group
Experimental Group Dihydroartesiminin Piperaquine Weight based, once a day 3 days Dihydroartemisinin-Piperaquine will be administered at a target dose (range) of 4 (2.5-10) mg/kg body weight per day Dihydroartemisinin, and 24 (20-32) mg/kg body weight per day piperaquine once a day for three days for children weighing <25kg. The target doses and ranges for children weighing ≥25 kg are 4 mg/kg (2-10) body weight per day dihydroartemisinin and 18 (16-27) mg/kg body weight per day piperaquine given once a day for three days. The correct drug dosage will be determined from the dosing chart. 250
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Age between 6 months to 10 years. 2. Mono-infection with P. falciparum confirmed by positive blood film (i.e., No mixed infection). 3. Parasitaemia of 1,000 – 100,000/μl asexual forms. 4. Presence of axillary temperature ≥ 37.5°c or history of fever during the past 24 hours. 5. Ability to swallow and retain oral medication. 6. Haemoglobin ≥8.0 g/dL. 7. Informed consent from a parent or guardian. 8. Parent or guardian agrees to bring the child for the completion of AL or DHP doses and planned follow-up visits on days 7, 14, 21, 28, 35, and 42. Parent or guardian also agrees to bring the child back to the clinic (or agrees to hospitalization for three days) to ensure administration of all doses of treatment, or have a community health promoter (CHP) or study staff visit them at home to administer all evening doses of AL. 9. Live or plan to stay within the catchment area (within a 15 km radius of the sub-county hospital) of the study site for the next three months. 10. Ability and willingness to comply with the protocol for the duration of the study. 11. Parent or caregiver has access to a phone so that study staff may contact them during study period for visit reminders. 12. Children who have received the malaria vaccine (RTS,S/R21) or monoclonal antibody (L9LS) in the study area will be eligible to participate, but vaccination status will not be an inclusion or exclusion criterion. Receipt of either of these preventative pharmaceutical interventions will be recorded at enrollment. 1. Presence of general danger signs or signs of severe P. falciparum malaria according to the definitions of WHO (Appendix 2). 2. History of receiving any antimalarial treatment or antibiotics with antimalarial activity in the preceding 2 weeks from any source outside the study team. 3. Weight < 5 kg. 4. Haemoglobin < 8g/dL. 5. Mixed or mono-infection with another Plasmodium species detected by microscopy. 6. Presence of severe malnutrition according to WHO child growth standards (WHO, 2006), children with marasmus or edematous malnutrition. 7. Presence of febrile conditions due to diseases other than malaria (e.g., measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g., cardiac, renal and hepatic diseases, HIV/AIDS, sickle cell disease). 8. Medication, which may interfere with antimalarial pharmacokinetics. These include antiretroviral drugs, anti-epileptic drugs, certain anti-fungal and anti-TB medications (List in Appendix 4) 9. History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s). 10. Regular antimalarial use for prophylaxis. These include use for malaria chemoprevention, e.g., in sickle cell disease, post-discharge malaria chemoprevention, etc. 11. Participating in another clinical trial. 12. Plan to travel or leave the study catchment area within the next three months. Child: 6 Year-12 Year,Infant: 1 Month(s)-12 Month(s),Preschool Child: 2 Year-5 Year 6 Month(s) 10 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 17/06/2026 Kenya Medical Research Institute Scientific Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Off Raila Odinga Way Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. To assess the therapeutic efficacy of Artemether-Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) for the treatment of uncomplicated P. falciparum malaria. 2. To measure the clinical and parasitological efficacy of AL and DHP in patients aged between 6 months and 10 years, diagnosed with uncomplicated P. falciparum malaria by determining the proportion with early treatment failure, late clinical failure, late parasitological failure, or adequate clinical and parasitological response as indicators of efficacy. 42 days post enrollment
Secondary Outcome 1. To assess the frequency of existing molecular markers associated with anti-malarial drug resistance, identify new molecular markers, and frequency of evasion of HRP2-based rapid diagnostic tests (RDT). 2. To evaluate the incidence of adverse/severe adverse events after treatment with AL and DHP. 3. Evaluate duration of malaria HRP2/pLDH RDT positivity after appropriate treatment with AL and DP (if funding allows) 42 days post enrollment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI CGHR 1578 Kisumu 40100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
PATH 437N 34th Street Seattle WA98103 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor PATH 437N 34th Street Seattle WA 98103 United States of America International NGO
COLLABORATORS
Name Street address City Postal code Country
CDC 1600 Clifton Road NE Atlanta GA 30329 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Dennis Bii denniskbii@gmail.com +254722401773 Off Kisumu-Busia Road
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Research Scientist KEMRI
Role Name Email Phone Street address
Public Enquiries Samuel Mahugu drsammymahugu@gmail.com +254726350808 Off Hospital Road
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya National Malaria Control Programme
Role Name Email Phone Street address
Scientific Enquiries Simon Kariuki skariuki1578@gmail.com +254725389246 Off Kisumu-Busia Road
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Senior Principal Research Scientist KEMRI
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All of the individual participant data collected during the trial, after deidentification. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Beginning 3 months and ending 5 years following article publication. Investigators whose proposed use of the data has been approved by an independent review committee.
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