Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

Autor:	Nickols NG; Radiation Oncology Service, VA Greater Los Angeles Healthcare System, Los Angeles, California.; Department of Radiation Oncology, University of California, Los Angeles.; Department of Urology, University of California, Los Angeles., Mi Z; VA Cooperative Studies Program Coordinating Center, Perry Point, Maryland., DeMatt E; VA Cooperative Studies Program Coordinating Center, Perry Point, Maryland., Biswas K; VA Cooperative Studies Program Coordinating Center, Perry Point, Maryland., Clise CE; VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico., Huggins JT; Pulmonary and Critical Care Medicine, Ralph H. Johnson VA Medical Center, Charleston, South Carolina.; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston., Maraka S; Medicine Service, Central Arkansas Veterans Healthcare System, Little Rock.; Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock., Ambrogini E; Medicine Service, Central Arkansas Veterans Healthcare System, Little Rock.; Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock., Mirsaeidi MS; Division of Pulmonary, Critical Care and Sleep, College of Medicine-Jacksonville, University of Florida, Jacksonville., Levin ER; Division of Endocrinology, Long Beach VA Medical Center, Long Beach, California.; Division of Endocrinology, Department of Medicine, University of California, Irvine., Becker DJ; Division of Hematology and Oncology VA New York Harbor Healthcare System, Manhattan Campus, New York.; Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York., Makarov DV; VA New York Harbor Healthcare System, Manhattan Campus, New York.; NYU Grossman School of Medicine, New York, New York., Adorno Febles V; VA New York Harbor Healthcare System, Manhattan Campus, New York.; NYU Grossman School of Medicine, New York, New York., Belligund PM; VA New York Harbor Healthcare System, Brooklyn Campus, Brooklyn., Al-Ajam M; VA New York Harbor Healthcare System, Brooklyn Campus, Brooklyn., Muthiah MP; Veterans Affairs Medical Center, Memphis, Tennessee.; University of Tennessee Health Science Center, Memphis., Montgomery RB; Division of Hematology and Oncology, VA Puget Sound Health Care System, Seattle, Washington.; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle., Robinson KW; Department of Hematology and Oncology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania.; Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia., Wong YN; Department of Hematology and Oncology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania.; Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia., Bedimo RJ; VA North Texas Health Care System, Dallas.; UT Southwestern Medical Center, School of Medicine, Dallas, Texas., Villareal RC; Michael E. DeBakey VA Medical Center, Houston, Texas., Aguayo SM; Pulmonary and Critical Care Medicine, Phoenix VA Health Care System, Phoenix, Arizona., Schoen MW; John Cochran Veterans Affairs Medical Center, St Louis, Missouri.; Department of Medicine, Saint Louis University School of Medicine, St Louis, Missouri., Goetz MB; Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, California.; Department of Medicine, University of California, Los Angeles., Graber CJ; Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, California., Bhattacharya D; Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, California., Soo Hoo G; Pulmonary, Critical Care and Sleep Section, VA Greater Los Angeles Healthcare System, Los Angeles, California., Orshansky G; Department of Medicine, University of California, Los Angeles.; Clinical Informatics, VA Greater Los Angeles Healthcare System, Los Angeles, California., Norman LE; VA Cooperative Studies Program Coordinating Center, Perry Point, Maryland., Tran S; Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California., Ghayouri L; Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California., Tsai S; Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California., Geelhoed M; Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California., Rettig MB; Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California.; Departments of Medicine and Urology, University of California, Los Angeles.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2022 Apr 01; Vol. 5 (4), pp. e227852. Date of Electronic Publication: 2022 Apr 01.
DOI:	10.1001/jamanetworkopen.2022.7852
Abstrakt:	Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2. Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19. Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021. Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone. Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days. Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns. Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity. Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.
Databáze:	MEDLINE
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