Does androgen suppression improve clinical outcomes in hospitalized men with COVID-19?
In this randomized clinical trial including 96 men, androgen suppression with the addition of degarelix vs placebo plus standard care did not show reduction of the composite end point of mortality, ongoing hospitalization, or requirement for mechanical ventilation at day 15 after randomization.
This randomized clinical trial found that androgen suppression did not improve outcomes in men hospitalized for COVID-19.
SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT04397718
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: February 18, 2022.
Published: April 19, 2022. doi:10.1001/jamanetworkopen.2022.7852
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Nickols NG et al. JAMA Network Open.
Corresponding Author: Matthew B. Rettig, MD, Division of Hematology-Oncology, Department of Medicine, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073 (firstname.lastname@example.org).
Author Contributions: Drs Rettig and Nickols had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Nickols, Mi, Biswas, Clise, Becker, Makarov, Muthiah, Aguayo, Goetz, Graber, Soo Hoo, Norman, Tran, Tsai, Rettig.
Acquisition, analysis, or interpretation of data: Nickols, Mi, DeMatt, Clise, Huggins, Maraka, Levin, Ambrogini, Mirsaeidi, Levin, Becker, Makarov, Adorno Febles, Belligund, Al-Ajam, Muthiah, Montgomery, Robinson, Wong, Bedimo, Armamento-Villareal, Aguayo, Schoen, Graber, Bhattacharya, Soo Hoo, Orshansky, Ghayouri, Geelhoed, Rettig.
Drafting of the manuscript: Nickols, Mi, Clise, Becker, Aguayo, Tran, Ghayouri, Tsai, Geelhoed, Rettig.
Critical revision of the manuscript for important intellectual content: Nickols, Mi, DeMatt, Biswas, Huggins, Maraka, Ambrogini, Mirsaeidi, Levin, Becker, Makarov, Adorno Febles, Belligund, Al-Ajam, Muthiah, Montgomery, Robinson, Wong, Bedimo, Armamento-Villareal, Aguayo, Schoen, Goetz, Graber, Bhattacharya, Soo Hoo, Orshansky, Norman, Rettig.
Statistical analysis: Mi, DeMatt.
Obtained funding: Nickols, Rettig.
Administrative, technical, or material support: Nickols, Mi, Biswas, Clise, Ambrogini, Becker, Makarov, Adorno Febles, Belligund, Al-Ajam, Montgomery, Robinson, Wong, Bedimo, Aguayo, Schoen, Goetz, Graber, Soo Hoo, Norman, Tran, Ghayouri, Tsai, Geelhoed, Rettig.
Supervision: Nickols, Huggins, Maraka, Becker, Makarov, Robinson, Wong, Armamento-Villareal, Aguayo, Bhattacharya, Rettig.
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.
Funding/Support: The trial was funded by the Department of Veterans Affairs (VA) Office of Research and Development through a CSR&D Merit Review Award (Dr Rettig).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.
Additional Information: Some VA sites in the trial were additionally supported by the Prostate Cancer Foundation as Centers of Excellence.
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