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 controlled trial
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
Affiliations
Nicholas G. Nickols
Radiation Oncology Service, VA Greater Los Angeles Healthcare System
Matthew B. Goetz
Infectious Diseases Section, VA Greater Los Angeles Healthcare System
Christopher J. Graber
Infectious Diseases Section, VA Greater Los Angeles Healthcare System
Debika Bhattacharya
Infectious Diseases Section, VA Greater Los Angeles Healthcare System
Guy Soo Hoo
Division of Pulmonary and Critical Care, VA Greater Los Angeles Healthcare System
Matthew Might
Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham
David B. Goldstein
Institute of Genomic Medicine, Columbia University Irving Medical Center
Xinchen Wang
Institute of Genomic Medicine, Columbia University Irving Medical Center
Rachel Ramoni
Office of Research and Development, Veterans Health Administration
Kenute Myrie
Office of Research and Development, Veterans Health Administration
Samantha Tran
Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System
Leila Ghayouri
Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System
Sonny Tsai
Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System
Michelle Geelhoed
Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System
Danil Makarov
Division of Hematology-Oncology, VA New York Harbor Healthcare System
Daniel J. Becker
Division of Hematology-Oncology, VA New York Harbor Healthcare System
Jun-Chieh Tsay
Division of Pulmonary and Critical Care, VA New York Harbor Healthcare System
Melissa Diamond
Division of Hematology-Oncology, VA New York Harbor Healthcare System
Asha George
Division of Hematology-Oncology, VA New York Harbor Healthcare System
Mohammad Al-Ajam
Division of Pulmonary and Critical Care, VA New York Harbor Healthcare System
Pooja Belligund
Division of Pulmonary and Critical Care, VA New York Harbor Healthcare System
R. Bruce Montgomery
Division of Hematology-Oncology, VA Puget Sound Healthcare System
Elahe A. Mostaghel
Geriatric Research Education and Clinical Care (GRECC), VA Puget Sound Health Care System
Carlie Sulpizio
Division of Hematology-Oncology, VA Puget Sound Healthcare System
Zhibao Mi
VA Cooperative Studies Program Coordinating Center
Ellen Dematt
VA Cooperative Studies Program Coordinating Center
Joseph Tadalan
VA Cooperative Studies Program Coordinating Center
Leslie E. Norman
VA Cooperative Studies Program Coordinating Center
Daniel Briones
VA Cooperative Studies Program Coordinating Center
Christina E. Clise
VA Cooperative Studies Program Coordinating Center
Zachary W. Taylor
VA Cooperative Research Pharmacy Coordinating Center
Jeffrey R. Huminik
VA Cooperative Research Pharmacy Coordinating Center
Kousick Biswas
VA Cooperative Studies Program Coordinating Center
Matthew B. Rettig
Division of Hematology-Oncology, VA Greater Los Angeles Healthcare System
Abstract Background 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. Methods 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. Discussion 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. Trial registration ClinicalTrials.gov NCT04397718. Registered on May 21, 2020
