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Randomized Controlled Trial
. 2022 Apr 1;5(4):e227852.
doi: 10.1001/jamanetworkopen.2022.7852.

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

Nicholas G Nickols  1   2   3 , Zhibao Mi  4 , Ellen DeMatt  4 , Kousick Biswas  4 , Christina E Clise  5 , John T Huggins  6   7 , Spyridoula Maraka  8   9 , Elena Ambrogini  8   9 , Mehdi S Mirsaeidi  10 , Ellis R Levin  11   12 , Daniel J Becker  13   14 , Danil V Makarov  15   16 , Victor Adorno Febles  15   16 , Pooja M Belligund  17 , Mohammad Al-Ajam  17 , Muthiah P Muthiah  18   19 , Robert B Montgomery  20   21 , Kyle W Robinson  22   23 , Yu-Ning Wong  22   23 , Roger J Bedimo  24   25 , Reina C Villareal  26 , Samuel M Aguayo  27 , Martin W Schoen  28   29 , Matthew B Goetz  30   31 , Christopher J Graber  30 , Debika Bhattacharya  30 , Guy Soo Hoo  32 , Greg Orshansky  31   33 , Leslie E Norman  4 , Samantha Tran  34 , Leila Ghayouri  34 , Sonny Tsai  34 , Michelle Geelhoed  34 , Mathew B Rettig  34   35
Affiliations
Randomized Controlled Trial

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

Nicholas G Nickols et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Nickols reported receiving grants from Lantheus, Bayer, and Janssen and personal fees from Oncolinea outside the submitted work. Dr Wong reported receiving grants from the Prostate Cancer Foundation during the conduct of the study. Dr Bedimo reported receiving grants from Merck and ViiV Healthcare and personal fees from Merck, ViiV Healthcare, Janssen, Gilead Sciences, and Theratechnologies outside the submitted work. Dr Rettig reported receiving grants from Johnson & Johnson, Bayer, and Pfizer and having a patent for Inhibitors of the N-Terminal Domain of the Androgen Receptor pending. No other disclosures were reported.

Figures

Figure.
Figure.. Patient Recruitment Flowchart
Complete reasons for exclusion are in eTable 2 in Supplement 2.
See this image and copyright information in PMC

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