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
| العنوان: | 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 |
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| المؤلفون: | Zhibao Mi, Jun-Chieh Tsay, Zachary W Taylor, Sonny Tsai, Daniel Briones, Christina E. Clise, R. Bruce Montgomery, Michelle Geelhoed, Matthew Bidwell Goetz, Leila Ghayouri, Jeffrey R Huminik, Carlie Sulpizio, Rachel Ramoni, Guy W. Soo Hoo, Xinchen Wang, Kousick Biswas, David Goldstein, Nicholas G. Nickols, Danil V. Makarov, Kenute Myrie, Melissa Diamond, Mohammad Al-Ajam, Matthew Rettig, Christopher J. Graber, Debika Bhattacharya, Joseph Tadalan, Matthew Might, Samantha Tran, Asha George, Elahe A. Mostaghel, Leslie E Norman, Pooja Belligund, Daniel J. Becker, Ellen DeMatt |
| المصدر: | Trials, Vol 22, Iss 1, Pp 1-8 (2021) Trials |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Anti-androgen, medicine.medical_specialty, Medicine (General), Androgen suppression, Medicine (miscellaneous), Placebo, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Study Protocol, 0302 clinical medicine, Clinical Trials, Phase II as Topic, R5-920, Randomized controlled trial, law, Internal medicine, Severity of illness, Clinical endpoint, Medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), 030212 general & internal medicine, Degarelix, Hormone therapy, TMPRSS2, Randomized Controlled Trials as Topic, Veterans, Host cell surface, business.industry, SARS-CoV-2, COVID-19, Clinical trial, Hospitalization, Coronavirus, Androgen receptor, 030104 developmental biology, Treatment Outcome, chemistry, business, Oligopeptides |
| الوصف: | 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 |
| اللغة: | English |
| تدمد: | 1745-6215 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88546453d6bdf5c5e6c45ed94df8fe64 https://doaj.org/article/62f781dbd78244d99ccb944f53f3ca94 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....88546453d6bdf5c5e6c45ed94df8fe64 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17456215 |
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