Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial

Trials

Study Protocol

Elliott Vichinsky¹  Hagar Wilkinson²  Deborah Leake²  Todd Chang³  Christopher Denton³  Angela Ellison⁴  Alexis Thompson⁴  Kathleen Brown⁵  Andrew Campbell⁵  Dunia Hatabah⁶  Carlton Dampier⁷  Claudia R. Morris⁷  Chris A. Rees⁷  David C. Brousseau⁸  Nitya Bakshi⁹  Keli D. Coleman^1,10  Anthony Villella^1,11  Daniel M. Cohen^1,11  Gladstone Airewele^1,12  Corrie E. Chumpitazi^1,12  Sara Leibovich^1,13  T. Charles Casper^1,14  Michelle Robinson^1,14  Fahd Ahmad^1,15 

[1] Center for Maternal-Fetal Precision Medicine, University of California, San Francisco, CA, USA;Department of Pediatrics, UCSF-Benioff Children’s Hospital-Oakland, Oakland, CA, USA;Children’s Healthcare of Atlanta, Atlanta, GA, USA;Children’s Hospital Los Angeles and Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;Children’s Hospital of Philadelphia, Philadelphia, PA, USA;Children’s National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA;Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine, 1760 Haygood Drive NE, W45830322, Atlanta, GA, USA;Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine, 1760 Haygood Drive NE, W45830322, Atlanta, GA, USA;Children’s Healthcare of Atlanta, Atlanta, GA, USA;Department of Pediatrics, Nemours Children’s Health Delaware and the Sidney Kimmel Medical College, Thomas Jefferson University, Wilmington, DE, USA;Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA;Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA;Medical College of Wisconsin and Children’s Wisconsin, Milwaukee, WI, USA;Nationwide Children’s Hospital, Columbus, OH, USA;Texas Children’s Hospital and Baylor College of Medicine, Houston, TX, USA;University of California, San Francisco, CA, USA;University of Utah School of Medicine, Salt Lake City, UT, USA;Washington University in St. Louis, St. Louis, MO, USA;

关键词: Sickle cell disease;    Arginine;    Vaso-occlusive pain;    Randomized controlled trial;   

DOI  :  10.1186/s13063-023-07538-z

 received in 2023-05-08, accepted in 2023-07-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDespite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.MethodsSTArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant’s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE.DiscussionBuilding on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children.Trial registrationThe STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354).

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 1

Fig. 1

13690_2023_1154_Article_IEq7.gif

Fig. 3