2. Academic Validation
  3. A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis

A randomized clinical trial of the efficacy and safety of rivipansel for sickle cell vaso-occlusive crisis

  • Blood. 2023 Jan 12;141(2):168-179. doi: 10.1182/blood.2022015797.
Carlton D Dampier 1 2 3,  Marilyn Jo Telen 4,  Ted Wun 5,  R Clark Brown 1 2 3,  Payal Desai 6,  Fuad El Rassi 7 8,  Beng Fuh 9,  Julie Kanter 10,  Yves Pastore 11 12,  Jennifer Rothman 13,  James G Taylor 14,  David Readett 15,  Krupa M Sivamurthy 15,  Brinda Tammara 15,  Li-Jung Tseng 16,  Jay Nelson Lozier 17,  Helen Thackray 17,  John L Magnani 17,  Kathryn L Hassell 18
Affiliations

Affiliations

  • 1 Department of Pediatrics, Emory University, Atlanta, GA.
  • 2 Aflac Cancer and Blood Disorders Center, Atlanta, GA.
  • 3 Children's Healthcare of Atlanta, Atlanta, GA.
  • 4 Division of Hematology, Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC.
  • 5 Division of Hematology Oncology, UC Davis School of Medicine, Sacramento, CA.
  • 6 James Comprehensive Cancer Hospital & Solove Research Institute, The Ohio State University Wexner Medical Center, The Ohio State University, Columbus, OH.
  • 7 Georgia Comprehensive Sickle Cell Center and Grady Health System, Atlanta, GA.
  • 8 Department of Medicine, Emory University, Atlanta, GA.
  • 9 East Carolina University Comprehensive Sickle Cell Center, Greenville, NC.
  • 10 Department of Medicine, University of Alabama, Birmingham, AL.
  • 11 CHU Sainte-Justine, Montreal, QC, Canada.
  • 12 Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
  • 13 Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC.
  • 14 Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC.
  • 15 Pfizer Inc, Collegeville, PA.
  • 16 Pfizer Inc, New York, NY.
  • 17 GlycoMimetics Inc, Rockville, MD.
  • 18 Division of Hematology, University of Colorado, Aurora, CO.
PMID: 35981565 DOI: 10.1182/blood.2022015797
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).

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