Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19 A Randomized, Controlled Pilot Trial

• Type of Material: Article
• Authors: DONALD STEIN, Emory University; Sara Ghandehari, Cedars Sinai Medical Center; Yuri Matusov, Cedars Sinai Medical Center; Samuel Pepkowitz, Cedars Sinai Medical Cente; Donald Stein, Emory University; Tamana Kaderi, Cedars Sinai Medical Center; Divya Narayanan, Cedars Sinai Medical Center; Josephine Hwang, Cedars Sinai Medical Center; Stephanie Chang, Cedars Sinai Medical Center; Robert Goodman, Cedars Sinai Medical Center; Heli Ghandehari, Independent biostatistical consultant, San Diego; James Mirocha, Cedars Sinai Medical Center; Catherin Bresee, Cedars Sinai Medical Center; Victor Tapson, Cedars Sinai Medical Center; Michael Lewis, Cedars Sinai Medical Center
• Language: English
• Date: 2021-07-07
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 American College of Chest Physicians.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chest.2021.02.024
• Title of Journal or Parent Work: CHEST
• Volume: 160
• Issue: 1
• Start Page: 74
• End Page: 84
• Grant/Funding Information: This study was partially sponsored by Institut Biochimique SA (IBSA, Lugano, Switzerland). IBSA provided the study drug and partially supported this investigator-initiated study financially.
• Keywords: WOMEN; General & Internal Medicine; Respiratory System; Life Sciences & Biomedicine; HORMONES; COVID-19; EXPRESSION; SEX-DIFFERENCES; progesterone; Critical Care Medicine; sex difference in COVID-19 outcomes; Science & Technology
• Research Categories: Health Sciences, Public Health; Health Sciences, General

Abstract

Background: Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. Research Question: Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19? Study Design and Methods: We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes. Results: Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P = .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects. Interpretation: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19. Trial Registry: ClinicalTrials.gov; No.: NCT04365127; URL: www.clinicaltrials.gov.