Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized control

Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity.

This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated.

In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19.

ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.

Trials. 2021 Jul 05*** epublish ***

Nicholas G Nickols, Matthew B Goetz, Christopher J Graber, Debika Bhattacharya, Guy Soo Hoo, Matthew Might, David B Goldstein, Xinchen Wang, Rachel Ramoni, Kenute Myrie, Samantha Tran, Leila Ghayouri, Sonny Tsai, Michelle Geelhoed, Danil Makarov, Daniel J Becker, Jun-Chieh Tsay, Melissa Diamond, Asha George, Mohammad Al-Ajam, Pooja Belligund, R Bruce Montgomery, Elahe A Mostaghel, Carlie Sulpizio, Zhibao Mi, Ellen Dematt, Joseph Tadalan, Leslie E Norman, Daniel Briones, Christina E Clise, Zachary W Taylor, Jeffrey R Huminik, Kousick Biswas, Matthew B Rettig

Radiation Oncology Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA., Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA., Division of Pulmonary and Critical Care, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA., Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, USA., Institute of Genomic Medicine, Columbia University Irving Medical Center, New York, USA., Office of Research and Development, Veterans Health Administration, Washington, D.C., USA., Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA., Division of Hematology-Oncology, VA New York Harbor Healthcare System, New York, USA., Division of Pulmonary and Critical Care, VA New York Harbor Healthcare System, New York, USA., Division of Hematology-Oncology, VA Puget Sound Healthcare System, Seattle, USA., Geriatric Research Education and Clinical Care (GRECC), VA Puget Sound Health Care System, Seattle, USA., VA Cooperative Studies Program Coordinating Center, Point, Perry, MD, USA., VA Cooperative Research Pharmacy Coordinating Center, Albuquerque, NM, USA., Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA. .

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