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.: PACTR202507605302954 Date of Registration: 01/07/2025
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Dihydroartemisinin-piperaquine + sulfadoxine-pyrimethamine for sickle cell anemia
Official scientific title Dihydroartemisinin-piperaquine plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone for the prevention of febrile illnesses in children with sickle cell anemia: a double-blind randomized controlled trial
Brief summary describing the background and objectives of the trial Although there is evidence that children with sickle cell anemia (SCA) have some protection against higher-density malaria infections, even low parasite density infections can precipitate crises, including severe anemia crises, painful crises, and acute chest syndrome. To reduce malaria-related morbidity in children with SCA, the World Health Organization (WHO) recommends malaria chemoprevention. However, optimal drug choices have not been identified. In Uganda, malaria chemoprevention with monthly doses of sulfadoxine-pyrimethamine (SP) is the current standard of care. However, the effectiveness of SP for chemoprevention is threatened by widespread antifolate resistance, especially in areas of eastern and central Africa. Dihydroartemisinin-piperaquine (DP), given monthly, has shown promising results in reducing symptomatic malaria, though it lacks the antibacterial benefits of SP. Combining DP plus SP for chemoprevention in children with SCA could reduce both malaria and non-malaria febrile illnesses. However, there are no data to support the use of this novel intervention. In this study, we will test the hypothesis that chemoprevention with monthly DP+SP is safe and more protective against all-cause febrile illnesses in children with SCA compared to monthly SP alone (the current standard of care). The specific objectives of the study are to 1) compare the incidence of all-cause febrile illness among children with SCA randomized to receive monthly SP vs. DP+SP; 2) compare the incidence of adverse events among children with SCA randomized to monthly SP vs. DP+SP; and 3) compare the prevalence of markers of antimalarial resistance, including those associated with SP and DP resistance, among children infected with malaria parasites randomized to monthly SP vs. DP+SP.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) DIPPS
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria,Sickle cell anemia and febrile illnesses
Purpose of the trial Prevention
Anticipated trial start date 01/07/2025
Actual trial start date 11/02/2026
Anticipated date of last follow up 30/07/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 232
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
Experimental Group Dihydroartemisinin piperaquine plus sulfadoxine pyrimethamine Every 4 weeks One year The intervention will consist of dihydroartemisinin piperaquine plus sulfadoxine pyrimethamine (DP+SP) given every 4 weeks. Every 4 weeks, children assigned to the intervention arm will be given a single dose of SP and a three-day dose of DP (D-ARTEPP® Dispersible, Guilin Pharmaceutical Company, China) based on bodyweight following the WHO and the manufacturer’s recommendation. 116
Control Group Sulfadoxine pyrimethamine Given once every 4 weeks For one year Children in the control arm will receive a single dose of SP (Kamsidar, 500 mg sulfadoxine/25 mg pyrimethamine tablets, Kampala Pharmaceutical Industries, Uganda, or Guilin Pharmaceutical Company, China) every 4 weeks. SP will be given following the Uganda Ministry of Health guidelines according to age (under 4 years will receive 1/2 tablet, 4 to less than 7 years 1 tablet, 7 to less than 10 years 1 ½ tablets, and 10 to 11 years 2 tablets) and will be administered by directly observed therapy. 116 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) Residence within Busia district or Tororo districts 2) Hemoglobin SS genotype by hemoglobin electrophoresis 3) Age between 2-10 years 4) Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol where possible 5) Provision of informed consent from parent/guardian and assent if children are ≥8 years of age 1) HIV infected 2) Planning to leave the study area during the study period. 3) History of allergy or serious drug reaction to SP or DP Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 2 Year(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 14/07/2025 Joint Clinical Research Centre Research Ethics Committe
Ethics Committee Address
Street address City Postal code Country
Lubowa, Entebbe Road Kampala 10005 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Incidence of all-cause febrile illnesses defined as an incident episode of subjective fever in the past 24 hours or axillary temperature >37.5°C. Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Primary Outcome Incidence of any grade 3-4 adverse events or serious adverse events Time at risk will begin the day study drugs are first given and will end when study participants complete one year of follow-up or early study termination
Primary Outcome Prevalence of resistance markers of high-grade antifolate resistance (Pfdhfr 164L and fdhps 581G). Samples with microscopic parasitemia obtained during the 1-year of follow-up
Secondary Outcome Incidence of documented fever, defined as all clinic visits during the follow-up period with an incident episode of axillary temperature >37.5°C. Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of symptomatic malaria defined as a new episode of fever plus a positive blood smear not preceded by another episode in the last 14 days. Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of pneumonia Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of all-cause hospitalizations Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of blood transfusions Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of all-cause sick visits Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of sickle cell crises Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of all-cause deaths Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Prevalence of malaria parasitemia Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Prevalence of moderate-severe anemia defined as hemoglobin level less than 8g/dL Time at risk will begin one day after administration of the first dose of study drugs and will end when the study participants complete one year of follow-up or upon early study termination.
Secondary Outcome Incidence of individual grade 3-4 adverse events Time at risk will begin the day study drugs are first given and will end when study participants complete one year of follow-up or early study termination.
Secondary Outcome Incidence of adverse events related to study drugs Time at risk will begin the day study drugs are first given and will end when study participants complete one year of follow-up or early study termination.
Secondary Outcome Incidence of individual adverse events of any severity Time at risk will begin the day study drugs are first given and will end when study participants complete one year of follow-up or early study termination.
Secondary Outcome Prevalence of observed or reported vomiting following administration of study drugs Time at risk will begin the day study drugs are first given and will end when study participants complete one year of follow-up or early study termination.
Secondary Outcome Measures of non-adherence with study drugs defined as the proportion of study drug doses to be administered at home reported not taken. Time at risk will begin the day study drugs are first given and will end when study participants complete one year of follow-up or early study termination.
Secondary Outcome Prevalence of DP resistance: PfK13 561H, 469Y, 675V and/or PfCRT 76T. Samples with microscopic parasitemia obtained during 1-year of follow-up
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
IDRC Site Masafu General Hospital Majanji Road Busia District Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Thrasher Research Fund 68 S. Main Street, Suite 400 Salt Lake City 84101 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Thrasher Research Fund 68 S. Main Street, Suite 400 Salt Lake City 84101 United States of America Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Dr Richard Idro Makerere University College of Health Sciences Kampala Uganda
Grant Dorsey San Francisco General Hospital, 995 Potrero Avenue San Francisco United States of America
Philip Rosenthal San Francisco General Hospital, 995 Potrero Avenue San Francisco United States of America
Michelle Hsiang 550 16th Street San Francisco 94158 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Amanda Atukunda aatukunda@idrc-uganda.org +256703428466 2C Nakasero Hill Road
City Postal code Country Position/Affiliation
Kampala Uganda Communications coordinator
Role Name Email Phone Street address
Principal Investigator Abel Kakuru akakuru@idrc-uganda.org +256783545585 2C Nakasero Hill Road
City Postal code Country Position/Affiliation
Kampala Uganda Medical Epidemiologist
Role Name Email Phone Street address
Scientific Enquiries Abel Kakuru akakuru@idrc-uganda.org +256783545585 2C Nakasero Hill Road
City Postal code Country Position/Affiliation
Kampala Uganda Medical Epidemiologist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes After completion of the study and publication of the analyzed data, the dataset will be shared on a public data-sharing platform such as ClinEpiDB, where it will be made accessible to other researchers. Statistical Analysis Plan,Study Protocol The data will be shared after study completion, data analysis, and publication of the results through a public data-sharing platform such as ClinEpiDB It will be freely available
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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 26/03/2026 To update the date of starting enrollment. 11 Feb 2026
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 26/03/2026 This revision is to reflect the anticipated date of last participant enrollment, expected in June-July 2026 31 Dec 2026 30 Jul 2027
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 26/03/2026 We have now started enrollment. Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/03/2026 To update the ethics approval status. The study is now approved. FALSE, Joint Clinical Research Centre Research Ethics Committe, Lubowa, Entebbe Road, Kampala, 10005, Uganda, 22 May 2025, , 256417723000, jcrc@jcrc.org.ug, 34871_32034_4737.pdf TRUE, Joint Clinical Research Centre Research Ethics Committe, Lubowa, Entebbe Road, Kampala, 10005, Uganda, 22 May 2025, 14 Jul 2025, 256417723000, jcrc@jcrc.org.ug, 34871_32034_4737.pdf