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

Autor:	Casella JF; Johns Hopkins University School of Medicine, Baltimore, Maryland., Barton BA; University of Massachusetts Medical School, Worcester., Kanter J; Medical University of South Carolina, Charleston.; University of Alabama at Birmingham, Birmingham., Black LV; Our Lady of the Lake Regional Medical Center, Baton Rouge, Louisiana.; University of Florida College of Medicine, Gainesville., Majumdar S; University of Mississippi Medical Center, Jackson.; Children's National Hospital, Washington, DC., Inati A; Lebanese American University, Byblos and Beirut, Lebanon.; Nini Hospital, Tripoli, Lebanon., Wali Y; Sultan Qaboos University, Muscat, Oman., Drachtman RA; Rutgers University, New Brunswick, New Jersey., Abboud MR; American University of Beirut Medical Center, Beirut, Lebanon., Kilinc Y; Çukurova University Medical Faculty Balcali Hospital, University of Çukurova, Adana, Turkey., Fuh BR; East Carolina University, Greenville, North Carolina., Al-Khabori MK; Sultan Qaboos University, Muscat, Oman., Takemoto CM; Johns Hopkins University School of Medicine, Baltimore, Maryland.; St Jude Children's Research Hospital, Memphis, Tennessee., Salman E; Golisano Children's Hospital of Southwest Florida, Ft Myers., Sarnaik SA; Wayne State University School of Medicine, Detroit, Michigan.; Children's Hospital of Michigan, Detroit., Shah N; Duke University School of Medicine, Durham, North Carolina., Morris CR; Emory University School of Medicine, Atlanta, Georgia.; Children's Healthcare of Atlanta, Atlanta, Georgia., Keates-Baleeiro J; T.C. Thompson Children's Hospital at Erlanger, University of Tennessee, Chattanooga., Raj A; University of Louisville/Norton Children's Hospital, Louisville, Kentucky., Alvarez OA; University of Miami, Miami, Florida., Hsu LL; University of Illinois at Chicago, Chicago., Thompson AA; Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Evanston, Illinois., Sisler IY; Children's Hospital of Richmond at Virginia Commonwealth University, Richmond., Pace BS; Augusta University, Augusta, Georgia., Noronha SA; University of Rochester School of Medicine and Dentistry, Golisano Children's Hospital at University of Rochester Medical Center, Rochester, New York., Lasky JL 3rd; Harbor-UCLA Medical Center, Torrance, California.; Cure 4 The Kids Foundation, Las Vegas, Nevada., de Julian EC; Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain., Godder K; Nicklaus Children's Hospital, Miami, Florida., Thornburg CD; Rady Children's Hospital - San Diego, San Diego, California.; UC San Diego School of Medicine, La Jolla, California., Kamberos NL; University of Iowa Children's Hospital, Iowa City.; Loyola University Medical Center, Maywood, Illinois., Nuss R; Children's Hospital Colorado, University of Colorado, Aurora., Marsh AM; UCSF Benioff Children's Hospital Oakland (UBCHO), Oakland, California.; University of Wisconsin-Madison, Madison., Owen WC; Children's Hospital of the King's Daughters, Norfolk, Virginia., Schaefer A; Joe DiMaggio Children's Hospital, Hollywood, Florida., Tebbi CK; Tampa General Hospital, Tampa, Florida., Chantrain CF; Clinique MontLegia, CHC, Liège, Belgium., Cohen DE; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.; Studer Family Children's Hospital Ascension Sacred Heart, University of Florida, Pensacola., Karakas Z; Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Piccone CM; Rainbow Babies and Children's Hospital, Cleveland, Ohio.; Carle Foundation Hospital, Urbana, Illinois., George A; Baylor College of Medicine, Houston, Texas.; Wake Forest School of Medicine, Winston-Salem, North Carolina., Fixler JM; The Herman and Walter Samuelson Children's Hospital at Sinai, Baltimore, Maryland., Singleton TC; Tulane University, New Orleans, Louisiana.; Mississippi Center for Advanced Medicine, Slidell, Louisiana., Moulton T; Bronx-Lebanon Hospital, Bronx, New York City, New York.; Bayer Pharmaceuticals, Whippany, New Jersey., Quinn CT; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., de Castro Lobo CL; Instituto estadual de Hematologia Arthur de Siqueira Cavalcanti - HEMORIO, Rio de Janeiro, Brasil., Almomen AM; Blood and Cancer Center, King Khalid University Hospital (KKUH), King Saud University Medical City, Riyadh, Saudi Arabia., Goyal-Khemka M; Phoenix Children's Hospital, Phoenix, Arizona.; Rutgers Cancer Institute of New Jersey, New Brunswick., Maes P; University Hospital of Antwerp (UZA), Edegem, Belgium., Emanuele M; Visgenx, San Diego, California.; Mast Therapeutics Inc, San Diego, California., Gorney RT; Johns Hopkins University School of Medicine, Baltimore, Maryland., Padgett CS; Mast Therapeutics Inc, San Diego, California.; Sanifit Therapeutics, San Diego, California., Parsley E; Mast Therapeutics Inc, San Diego, California.; Biotechnology, San Diego, California., Kronsberg SS; University of Massachusetts Medical School, Worcester., Kato GJ; CSL Behring, King of Prussia, Pennsylvania.; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania., Gladwin MT; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2021 Apr 20; Vol. 325 (15), pp. 1513-1523.
DOI:	10.1001/jama.2021.3414
Abstrakt:	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.
Databáze:	MEDLINE
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