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Blood

Title:		A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis
Author(s):		Dampier CD; Telen MJ; Wun T; Brown RC; Desai P; El Rassi F; Fuh B; Kanter J; Pastore Y; Rothman J; Taylor JG; Readett D; Sivamurthy KM; Tammara B; Tseng LJ; Lozier JN; Thackray H; Magnani JL; Hassell KL; Investigators R;
Address:		"Department of Pediatrics, Emory University, Atlanta, GA. Aflac Cancer and Blood Disorders Center, Atlanta, GA. Children's Healthcare of Atlanta, Atlanta, GA. Division of Hematology, Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC. Division of Hematology Oncology, UC Davis School of Medicine, Sacramento, CA. James Comprehensive Cancer Hospital & Solove Research Institute, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH. Georgia Comprehensive Sickle Cell Center and Grady Health System, Atlanta, GA. Department of Medicine, Emory University, Atlanta, GA. East Carolina University Comprehensive Sickle Cell Center, Greenville, NC. Department of Medicine, University of Alabama, Birmingham, AL. CHU Sainte-Justine, Montreal, QC, Canada. Department of Pediatrics, University of Montreal, Montreal, QC, Canada. Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC. Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC. Pfizer Inc, Collegeville, PA. Pfizer Inc, New York, NY. GlycoMimetics Inc, Rockville, MD. Division of Hematology, University of Colorado, Aurora, CO"
Journal Title:		Blood
Year:		2023
Volume:		141
Issue:		2
Page Number:		168 - 179
DOI:		10.1182/blood.2022015797
ISSN/ISBN:		1528-0020 (Electronic) 0006-4971 (Linking)
Abstract:		"The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) were randomized and 320 were treated (162 with rivipansel, 158 with placebo) with an IV loading dose, followed by up to 14 additional 12-hourly maintenance doses of rivipansel or placebo, in addition to standard care. Rivipansel was similarly administered during subsequent VOCs in the Open-label Extension (OLE) study. In the full analysis population, the median time to readiness for discharge (TTRFD), the primary end point, was not different between rivipansel and placebo (-5.7 hours, P = .79; hazard ratio, 0.97), nor were differences seen in secondary end points of time to discharge (TTD), time to discontinuation of IV opioids (TTDIVO), and cumulative IV opioid use. Mean soluble E-selectin decreased 61% from baseline after the loading dose in the rivipansel group, while remaining unchanged in the placebo group. In a post hoc analysis, early rivipansel treatment within 26.4 hours of VOC pain onset (earliest quartile of time from VOC onset to treatment) reduced median TTRFD by 56.3 hours, reduced median TTD by 41.5 hours, and reduced median TTDIVO by 50.5 hours, compared with placebo (all P < .05). A similar subgroup analysis comparing OLE early-treatment with early-treatment RESET placebo showed a reduction in TTD of 23.1 hours (P = .062) and in TTDIVO of 30.1 hours (P = .087). Timing of rivipansel administration after pain onset may be critical to achieving accelerated resolution of acute VOC. Trial Registration: Clinicaltrials.gov, NCT02187003 (RESET), NCT02433158 (OLE)"
Keywords:		"Adult Child Humans E-Selectin/therapeutic use *Anemia, Sickle Cell/complications/drug therapy *Volatile Organic Compounds/therapeutic use Pain/drug therapy/etiology Analgesics, Opioid/therapeutic use *Hemoglobinopathies Double-Blind Method;"
Notes:		"MedlineDampier, Carlton D Telen, Marilyn Jo Wun, Ted Brown, R Clark Desai, Payal El Rassi, Fuad Fuh, Beng Kanter, Julie Pastore, Yves Rothman, Jennifer Taylor, James G Readett, David Sivamurthy, Krupa M Tammara, Brinda Tseng, Li-Jung Lozier, Jay Nelson Thackray, Helen Magnani, John L Hassell, Kathryn L eng Clinical Trial, Phase III Randomized Controlled Trial Research Support, Non-U.S. Gov't 2022/08/19 Blood. 2023 Jan 12; 141(2):168-179. doi: 10.1182/blood.2022015797"