Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.
| Title: | Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial. |
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| Authors: | 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. |
| Source: | JAMA [JAMA] 2021 Apr 20; Vol. 325 (15), pp. 1513-1523. |
| Publication Type: | Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Medical Association Country of Publication: United States NLM ID: 7501160 Publication Model: Print Cited Medium: Internet ISSN: 1538-3598 (Electronic) Linking ISSN: 00987484 NLM ISO Abbreviation: JAMA Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chicago : American Medical Association, 1960- |
| MeSH Terms: | Anemia, Sickle Cell/*drug therapy ; Pain/*drug therapy ; Poloxamer/*therapeutic use ; Vasodilator Agents/*therapeutic use; Analgesics, Opioid/therapeutic use ; Anemia, Sickle Cell/complications ; Pain/etiology ; Placebos/adverse effects ; Placebos/therapeutic use ; Poloxamer/adverse effects ; Vasodilator Agents/adverse effects ; Adolescent ; Adult ; Child ; Double-Blind Method ; Female ; Humans ; Male ; Young Adult |
| 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. |
| Comments: | Comment in: JAMA. 2021 Apr 20;325(15):1524. doi: 10.1001/jama.2021.3399.. (PMID: 33877286); Comment in: JAMA. 2021 Sep 14;326(10):975. doi: 10.1001/jama.2021.11100.. (PMID: 34519808); Comment in: JAMA. 2021 Sep 14;326(10):974-975. doi: 10.1001/jama.2021.11097.. (PMID: 34519809) |
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| Molecular Sequence: | ClinicalTrials.gov NCT01737814 |
| Substance Nomenclature: | 0 (Analgesics, Opioid); 0 (Placebos); 0 (Vasodilator Agents); 106392-12-5 (Poloxamer) |
| Entry Date(s): | Date Created: 20210420 Date Completed: 20210505 Latest Revision: 20211022 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8058640 |
| DOI: | 10.1001/jama.2021.3414 |
| PMID: | 33877274 |
| Database: | MEDLINE |
Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't