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Publications

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Ppublish 31 citations

PubMed: 33877274 DOI: 10.1001/jama.2021.3414

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

JAMA 325(15):1513-1523

Authors: James F Casella, Bruce A Barton, Julie Kanter, L Vandy Black, Suvankar Majumdar, Adlette Inati, Yasser Wali, Richard A Drachtman, Miguel R Abboud, Yurdanur Kilinc, Beng R Fuh, Murtadha K Al-Khabori, Clifford M Takemoto, Emad Salman, Sharada A Sarnaik, Nirmish Shah, Claudia R Morris, Jennifer Keates-Baleeiro, Ashok Raj, Ofelia A Alvarez, Lewis L Hsu, Alexis A Thompson, India Y Sisler, Betty S Pace, Suzie A Noronha, Joseph L Lasky, Elena Cela de Julian, Kamar Godder, Courtney Dawn Thornburg, Natalie L Kamberos, Rachelle Nuss, Anne M Marsh, William C Owen, Anne Schaefer, Cameron K Tebbi, Christophe F Chantrain, Debra E Cohen, Zeynep Karakas, Connie M Piccone, Alex George, Jason M Fixler, Tammuella C Singleton, Thomas Moulton, Charles T Quinn, Clarisse Lopes de Castro Lobo, Abdulkareem M Almomen, Meenakshi Goyal-Khemka, Philip Maes, Marty Emanuele, Rebecca T Gorney … and 5 other authors

Affiliations

  • Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • University of Massachusetts Medical School, Worcester.
  • Medical University of South Carolina, Charleston.
  • University of Alabama at Birmingham, Birmingham.
  • Our Lady of the Lake Regional Medical Center, Baton Rouge, Louisiana.
  • University of Florida College of Medicine, Gainesville.
  • University of Mississippi Medical Center, Jackson.
  • Children's National Hospital, Washington, DC.
  • Lebanese American University, Byblos and Beirut, Lebanon.
  • Nini Hospital, Tripoli, Lebanon.
  • Sultan Qaboos University, Muscat, Oman.
  • Rutgers University, New Brunswick, New Jersey.
  • American University of Beirut Medical Center, Beirut, Lebanon.
  • Çukurova University Medical Faculty Balcali Hospital, University of Çukurova, Adana, Turkey.
  • East Carolina University, Greenville, North Carolina.
  • St Jude Children's Research Hospital, Memphis, Tennessee.
  • Golisano Children's Hospital of Southwest Florida, Ft Myers.
  • Wayne State University School of Medicine, Detroit, Michigan.
  • Children's Hospital of Michigan, Detroit.
  • Duke University School of Medicine, Durham, North Carolina.
  • Emory University School of Medicine, Atlanta, Georgia.
  • Children's Healthcare of Atlanta, Atlanta, Georgia.
  • T.C. Thompson Children's Hospital at Erlanger, University of Tennessee, Chattanooga.
  • University of Louisville/Norton Children's Hospital, Louisville, Kentucky.
  • University of Miami, Miami, Florida.
  • University of Illinois at Chicago, Chicago.
  • Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Evanston, Illinois.
  • Children's Hospital of Richmond at Virginia Commonwealth University, Richmond.
  • Augusta University, Augusta, Georgia.
  • University of Rochester School of Medicine and Dentistry, Golisano Children's Hospital at University of Rochester Medical Center, Rochester, New York.
  • Harbor-UCLA Medical Center, Torrance, California.
  • Cure 4 The Kids Foundation, Las Vegas, Nevada.
  • Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain.
  • Nicklaus Children's Hospital, Miami, Florida.
  • Rady Children's Hospital - San Diego, San Diego, California.
  • UC San Diego School of Medicine, La Jolla, California.
  • University of Iowa Children's Hospital, Iowa City.
  • Loyola University Medical Center, Maywood, Illinois.
  • Children's Hospital Colorado, University of Colorado, Aurora.
  • UCSF Benioff Children's Hospital Oakland (UBCHO), Oakland, California.
  • University of Wisconsin-Madison, Madison.
  • Children's Hospital of the King's Daughters, Norfolk, Virginia.
  • Joe DiMaggio Children's Hospital, Hollywood, Florida.
  • Tampa General Hospital, Tampa, Florida.
  • Clinique MontLegia, CHC, Liège, Belgium.
  • UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  • Studer Family Children's Hospital Ascension Sacred Heart, University of Florida, Pensacola.
  • Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • Rainbow Babies and Children's Hospital, Cleveland, Ohio.
  • Carle Foundation Hospital, Urbana, Illinois.
  • Baylor College of Medicine, Houston, Texas.
  • Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • The Herman and Walter Samuelson Children's Hospital at Sinai, Baltimore, Maryland.
  • Tulane University, New Orleans, Louisiana.
  • Mississippi Center for Advanced Medicine, Slidell, Louisiana.
  • Bronx-Lebanon Hospital, Bronx, New York City, New York.
  • Bayer Pharmaceuticals, Whippany, New Jersey.
  • Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
  • Instituto estadual de Hematologia Arthur de Siqueira Cavalcanti - HEMORIO, Rio de Janeiro, Brasil.
  • Blood and Cancer Center, King Khalid University Hospital (KKUH), King Saud University Medical City, Riyadh, Saudi Arabia.
  • Phoenix Children's Hospital, Phoenix, Arizona.
  • Rutgers Cancer Institute of New Jersey, New Brunswick.
  • University Hospital of Antwerp (UZA), Edegem, Belgium.
  • Visgenx, San Diego, California.
  • Mast Therapeutics Inc, San Diego, California.

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.

MeSH

Cells, Anemia, Sickle Cell, Pain, Thalassemia, Poloxamer, Therapeutics, Random Allocation, Child

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