The praziquantel in preschoolers (PIP) trial: study protocol for a phase II PK/PD-driven randomised controlled trial of praziquantel in children under 4 years of age

Trials

William W. Hope¹  Amaya L. Bustinduy²  Jennifer F. Friedman³  Hannah W. Wu³  Emily L. Webb⁴  Alison M. Elliott⁵  Andrew Edielu⁵  Patrice A. Mawa⁶  Moses Adriko⁷  Edridah M. Tukahebwa⁷  Alfred Mubangizi⁷  Narcis B. Kabatereine⁷ 

[1] Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool Health Partners, Liverpool, UK;Royal Liverpool, Broadgreen University Hospital Trust, Liverpool Health Partners, Liverpool, UK;Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK;Department of Pediatrics, Alpert Medical School of Brown University, Providence, RI, USA;Center for International Health Research, Lifespan Hospital, Providence, RI, USA;MRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK;MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda;Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK;MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda;Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda;Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK;Vector Control Division, Ministry of Health, Kampala, Uganda;

关键词: Praziquantel;    Preschool;    Children;    Intestinal schistosomiasis;    Schistosoma mansoni;    Schistosoma japonicum;   

DOI  :  10.1186/s13063-021-05558-1

来源: Springer

【 摘 要 】

BackgroundOver 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used “off label” in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis.MethodsWe will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12–47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters.DiscussionThe trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group.Trial registrationClinicalTrials.gov NCT03640377. Registered on 21 Aug 2018.

【 授权许可】

CC BY