[Skip to Navigation]
Original Investigation
April 20, 2021

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial

James F. Casella, MD1; Bruce A. Barton, PhD2; Julie Kanter, MD3,4; et al L. Vandy Black, MD, MSc5,6; Suvankar Majumdar, MD7,8; Adlette Inati, MD9,10; Yasser Wali, MD11; Richard A. Drachtman, MD12; Miguel R. Abboud, MD13; Yurdanur Kilinc, MD14; Beng R. Fuh, MD15; Murtadha K. Al-Khabori, MD11; Clifford M. Takemoto, MD1,16; Emad Salman, MD17; Sharada A. Sarnaik, MD18,19; Nirmish Shah, MD20; Claudia R. Morris, MD21,22; Jennifer Keates-Baleeiro, MD23; Ashok Raj, MD24; Ofelia A. Alvarez, MD25; Lewis L. Hsu, MD, PhD26; Alexis A. Thompson, MD, MPH27; India Y. Sisler, MD28; Betty S. Pace, MD29; Suzie A. Noronha, MD30; Joseph L. Lasky III, MD31,32; Elena Cela de Julian, MD, MSc, PhD33; Kamar Godder, MD34; Courtney Dawn Thornburg, MD, MS35,36; Natalie L. Kamberos, DO37,38; Rachelle Nuss, MD39; Anne M. Marsh, MD40,41; William C. Owen, MD42; Anne Schaefer, MD43; Cameron K. Tebbi, MD44; Christophe F. Chantrain, MD, PhD45; Debra E. Cohen, MD46,47; Zeynep Karakas, MD48; Connie M. Piccone, MD49,50; Alex George, MD51,52; Jason M. Fixler, MD53; Tammuella C. Singleton, MD54,55; Thomas Moulton, MD56,57; Charles T. Quinn, MD, MS58; Clarisse Lopes de Castro Lobo, MD, PhD59; Abdulkareem M. Almomen, MD60; Meenakshi Goyal-Khemka, MD61,62; Philip Maes, MD63; Marty Emanuele, PhD, MBA64,65; Rebecca T. Gorney, MS1; Claire S. Padgett, PhD65,66; Ed Parsley, DO65,67; Shari S. Kronsberg, MS2; Gregory J. Kato, MD68,69; Mark T. Gladwin, MD69
Author Affiliations
  • 1Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2University of Massachusetts Medical School, Worcester
  • 3Medical University of South Carolina, Charleston
  • 4University of Alabama at Birmingham, Birmingham
  • 5Our Lady of the Lake Regional Medical Center, Baton Rouge, Louisiana
  • 6University of Florida College of Medicine, Gainesville
  • 7University of Mississippi Medical Center, Jackson
  • 8Children’s National Hospital, Washington, DC
  • 9Lebanese American University, Byblos and Beirut, Lebanon
  • 10Nini Hospital, Tripoli, Lebanon
  • 11Sultan Qaboos University, Muscat, Oman
  • 12Rutgers University, New Brunswick, New Jersey
  • 13American University of Beirut Medical Center, Beirut, Lebanon
  • 14Çukurova University Medical Faculty Balcali Hospital, University of Çukurova, Adana, Turkey
  • 15East Carolina University, Greenville, North Carolina
  • 16St Jude Children’s Research Hospital, Memphis, Tennessee
  • 17Golisano Children’s Hospital of Southwest Florida, Ft Myers
  • 18Wayne State University School of Medicine, Detroit, Michigan
  • 19Children’s Hospital of Michigan, Detroit
  • 20Duke University School of Medicine, Durham, North Carolina
  • 21Emory University School of Medicine, Atlanta, Georgia
  • 22Children’s Healthcare of Atlanta, Atlanta, Georgia
  • 23T.C. Thompson Children’s Hospital at Erlanger, University of Tennessee, Chattanooga
  • 24University of Louisville/Norton Children’s Hospital, Louisville, Kentucky
  • 25University of Miami, Miami, Florida
  • 26University of Illinois at Chicago, Chicago
  • 27Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Evanston, Illinois
  • 28Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond
  • 29Augusta University, Augusta, Georgia
  • 30University of Rochester School of Medicine and Dentistry, Golisano Children’s Hospital at University of Rochester Medical Center, Rochester, New York
  • 31Harbor-UCLA Medical Center, Torrance, California
  • 32Cure 4 The Kids Foundation, Las Vegas, Nevada
  • 33Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain
  • 34Nicklaus Children’s Hospital, Miami, Florida
  • 35Rady Children’s Hospital - San Diego, San Diego, California
  • 36UC San Diego School of Medicine, La Jolla, California
  • 37University of Iowa Children’s Hospital, Iowa City
  • 38Loyola University Medical Center, Maywood, Illinois
  • 39Children’s Hospital Colorado, University of Colorado, Aurora
  • 40UCSF Benioff Children’s Hospital Oakland (UBCHO), Oakland, California
  • 41University of Wisconsin–Madison, Madison
  • 42Children’s Hospital of the King’s Daughters, Norfolk, Virginia
  • 43Joe DiMaggio Children’s Hospital, Hollywood, Florida
  • 44Tampa General Hospital, Tampa, Florida
  • 45Clinique MontLegia, CHC, Liège, Belgium
  • 46UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
  • 47Studer Family Children’s Hospital Ascension Sacred Heart, University of Florida, Pensacola
  • 48Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  • 49Rainbow Babies and Children’s Hospital, Cleveland, Ohio
  • 50Carle Foundation Hospital, Urbana, Illinois
  • 51Baylor College of Medicine, Houston, Texas
  • 52Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 53The Herman and Walter Samuelson Children’s Hospital at Sinai, Baltimore, Maryland
  • 54Tulane University, New Orleans, Louisiana
  • 55Mississippi Center for Advanced Medicine, Slidell, Louisiana
  • 56Bronx-Lebanon Hospital, Bronx, New York City, New York
  • 57Bayer Pharmaceuticals, Whippany, New Jersey
  • 58Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  • 59Instituto estadual de Hematologia Arthur de Siqueira Cavalcanti – HEMORIO, Rio de Janeiro, Brasil
  • 60Blood and Cancer Center, King Khalid University Hospital (KKUH), King Saud University Medical City, Riyadh, Saudi Arabia
  • 61Phoenix Children’s Hospital, Phoenix, Arizona
  • 62Rutgers Cancer Institute of New Jersey, New Brunswick
  • 63University Hospital of Antwerp (UZA), Edegem, Belgium
  • 64Visgenx, San Diego, California
  • 65Mast Therapeutics Inc, San Diego, California
  • 66Sanifit Therapeutics, San Diego, California
  • 67Biotechnology, San Diego, California
  • 68CSL Behring, King of Prussia, Pennsylvania
  • 69University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
JAMA. 2021;325(15):1513-1523. doi:10.1001/jama.2021.3414
Key Points

Question  Can poloxamer 188, an agent that is reported to reduce blood viscosity and cell-cell interactions, effectively reduce the duration of vaso-occlusive episodes (painful crises) in hospitalized patients with sickle cell disease?

Findings  In this randomized clinical trial that included 388 children and adults with sickle cell disease, treatment with poloxamer 188 vs placebo resulted in mean time to last dose of parenteral opioids during vaso-occlusive episodes of 81.8 vs 77.8 hours, a difference that was not statistically significant.

Meaning  Among patients with sickle cell disease, poloxamer 188 did not significantly shorten the duration of painful vaso-occlusive episodes.

Abstract

Importance  Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea.

Objective  To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes.

Design, Setting, and Participants  Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included.

Interventions  A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194).

Main Outcomes and Measures  Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup.

Results  Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, −7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%).

Conclusions and Relevance  Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes.

Trial Registration  ClinicalTrials.gov Identifier: NCT01737814

×