drugset / Trial / NCT07798583
OPTIMAL LEAP: Optimizing Dihydroartemisinin-Piperaquine IPTsc Intervals to Advance Learning, Executive Function, Attendance, and Antimalarial Resistance Surveillance in Kenyan Schoolchildren
Phase 3
Not yet recruiting
1500 enrolled
Indiana University
Broad Institute of MIT and Harvard · collabHarvard School of Public Health (HSPH) · collabJaramogi Oginga Odinga University of Science and Technology · collabKEMRI Centre for Global Health Research (CGHR), Kisumu, Kenya · collab
RandomizedParallel-groupSingle-blindPrevention
Summary
Malaria remains a major cause of illness among school-aged children in sub-Saharan Africa, many of whom carry asymptomatic Plasmodium falciparum infections that may contribute to anemia, inflammation, school absenteeism, and impaired cognitive performance. Intermittent preventive treatment in school-aged children (IPTsc) is recommended by the World Health Organization in settings with moderate-to-high malaria transmission, but the optimal dosing frequency remains uncertain. This cluster-randomized trial will compare monthly versus quarterly administration of dihydroartemisinin-piperaquine (DP) among 1,500 children aged 6-10 years attending six primary schools in Siaya County, Kenya. The primary objective is to determine whether monthly IPTsc results in greater improvements in executive functioning compared with quarterly IPTsc. Secondary objectives include evaluating effects on literacy, numeracy, school attendance, malaria infection, anemia, inflammatory and metabolic biomarkers, and molecular markers of antimalarial resistance.
Timeline
- Start
- 2028-01-01
- Primary completion
- 2030-01-01
- Completion
- 2033-01-01
Publications
- Background McHenry MS, Ayodo G, Marete I, Hasund CM, Knight V, Cunningham KB, Gaskin EL, White G, Tu W, Neafsey DE, John CC, Tran TM. Association of asymptomatic Plasmodium falciparum infections and its treatment with short-term cognitive performance in school-aged children: a prospective cohort study in western Kenya. J Infect. 2026 Aug 19:106831. doi: 10.1016/j.jinf.2026.106831. Online ahead of print.
- Background Kane J, Li X, Kumar S, Button-Simons KA, Brenneman KMV, Dahlhoff H, Sievert MAC, Checkley LA, Shoue DA, Singh PP, Abatiyow BA, Haile MT, Nair S, Reyes A, Tripura R, Peto T, Lek D, Kappe SHI, Dhorda M, Nkhoma SC, Cheeseman IH, Vaughan AM, Anderson TJC, Ferdig MT. A Plasmodium falciparum genetic cross reveals the contributions of pfcrt and plasmepsin II/III to piperaquine drug resistance. bioRxiv [Preprint]. 2023 Sep 17:2023.06.06.543862. doi: 10.1101/2023.06.06.543862.
- Background Amato R, Lim P, Miotto O, Amaratunga C, Dek D, Pearson RD, Almagro-Garcia J, Neal AT, Sreng S, Suon S, Drury E, Jyothi D, Stalker J, Kwiatkowski DP, Fairhurst RM. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis. 2017 Feb;17(2):164-173. doi: 10.1016/S1473-3099(16)30409-1. Epub 2016 Nov 3.
- Background McHenry MS, Mukherjee D, Bhavnani S, Kirolos A, Piper JD, Crespo-Llado MM, Gladstone MJ. The current landscape and future of tablet-based cognitive assessments for children in low-resourced settings. PLOS Digit Health. 2023 Feb 23;2(2):e0000196. doi: 10.1371/journal.pdig.0000196. eCollection 2023 Feb.
- Background Andrade CM, Fleckenstein H, Thomson-Luque R, Doumbo S, Lima NF, Anderson C, Hibbert J, Hopp CS, Tran TM, Li S, Niangaly M, Cisse H, Doumtabe D, Skinner J, Sturdevant D, Ricklefs S, Virtaneva K, Asghar M, Homann MV, Turner L, Martins J, Allman EL, N'Dri ME, Winkler V, Llinas M, Lavazec C, Martens C, Farnert A, Kayentao K, Ongoiba A, Lavstsen T, Osorio NS, Otto TD, Recker M, Traore B, Crompton PD, Portugal S. Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season. Nat Med. 2020 Dec;26(12):1929-1940. doi: 10.1038/s41591-020-1084-0. Epub 2020 Oct 26.
- Background Salgado C, Ayodo G, Macklin MD, Gould MP, Nallandhighal S, Odhiambo EO, Obala A, O'Meara WP, John CC, Tran TM. The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya. Malar J. 2021 Sep 17;20(1):371. doi: 10.1186/s12936-021-03905-w.
- Background Cohee LM, Opondo C, Clarke SE, Halliday KE, Cano J, Shipper AG, Barger-Kamate B, Djimde A, Diarra S, Dokras A, Kamya MR, Lutumba P, Ly AB, Nankabirwa JI, Njagi JK, Maiga H, Maiteki-Sebuguzi C, Matangila J, Okello G, Rohner F, Roschnik N, Rouhani S, Sissoko MS, Staedke SG, Thera MA, Turner EL, Van Geertruyden JP, Zimmerman MB, Jukes MCH, Brooker SJ, Allen E, Laufer MK, Chico RM. Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses. Lancet Glob Health. 2020 Dec;8(12):e1499-e1511. doi: 10.1016/S2214-109X(20)30325-9. Epub 2020 Oct 22.
- Background Clarke SE, Jukes MC, Njagi JK, Khasakhala L, Cundill B, Otido J, Crudder C, Estambale BB, Brooker S. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2008 Jul 12;372(9633):127-138. doi: 10.1016/S0140-6736(08)61034-X.
- Background Johnson AE, Upadhye A, Knight V, Gaskin EL, Turnbull LB, Ayuku D, Nyalumbe M, Abuonji E, John CC, McHenry MS, Tran TM, Ayodo G. Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition. J Pediatric Infect Dis Soc. 2024 May 30;13(5):288-296. doi: 10.1093/jpids/piae025.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | ARTENIMOL | Small molecule | — | — |
| Comparator | piperaquine | Small molecule | — | — |