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Progesterone in Addition to Standard of Care Versus Standard of Care Alone in the Treatment of Men Admitted to the Hospital with Moderate to Severe COVID-19: A Randomised Control Phase 1 Trial

23 Pages Posted: 13 Oct 2020

See all articles by Sara Ghandehari

Sara Ghandehari

Cedars Sinai Medical Center - Department of Medicine

Yuri Matusov

Cedars Sinai Medical Center - Department of Medicine

Samuel Pepkowitz

Cedars Sinai Medical Center - epartment of Pathology and Laboratory Medicine

Donald Stein

Emory University - Department of Emergency Medicine

Tamana Kaderi

Cedars Sinai Medical Center - Department of Medicine

Divya Narayanan

Cedars Sinai Medical Center - Department of Medicine

Josephine Hwang

Cedars Sinai Medical Center - Department of Medicine

Stephanie Chang

Cedars Sinai Medical Center - Department of Medicine

Robert Goodman

Cedars Sinai Medical Center - Department of Medicine

Heli Ghandehari

Independent

James Mirocha

Cedars Sinai Medical Center - Biostatistics Core

Catherine Bresee

Cedars Sinai Medical Center - Biostatistics Core

Victor Tapson

Cedars Sinai Medical Center - Department of Medicine

Michael Lewis

Cedars Sinai Medical Center - Department of Medicine

More...

Abstract

Background: Severity of illness and mortality from coronavirus disease 2019 (COVID-19) is consistently lower in women than in men. While this outcome difference is not well understood, focus on sex as a biologic factor may suggest potential therapeutic intervention for this disease. We assessed whether adding progesterone, a steroid hormone with immune-modulatory properties, to standard of care, would improve clinical outcomes of hospitalized men with moderate to severe COVID-19.

Method: We conducted a Phase 1, randomised, open-label, controlled trial at a large academic hospital in Los Angeles, CA, USA, of subcutaneous progesterone in men hospitalized with confirmed COVID-19 and evidence of lower respiratory tract involvement. Patients were randomly assigned (1:1), using block randomization and a computer-generated randomization sequence, to receive standard of care (SOC) plus progesterone (100 mg subcutaneously twice daily for up to five days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status based on a 7-point ordinal scale noted at baseline compared to that on Day 7 of the trial. Control patients with significant clinical deterioration or absence of clinical improvement by Day 7 were permitted to cross over to receive progesterone therapy. Intention to treat analysis was performed and the patient’s last clinical assessment prior to receiving the study drug was imputed as the Day 7 assessment.

Findings: Forty-two patients were enrolled in the study from April 27 to August 20, 2020; 22 were randomised to the control group and 20 to the progesterone group. Of the 20 patients in the progesterone group, two withdrew from the study prior to receiving progesterone and were excluded from analysis. There was an overall improvement in clinical status from baseline to Day 7 in patients in the progesterone group as compared to controls (95% CI: 0-2; P = 0·010). There were no serious adverse events attributable to progesterone.

Interpretation: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to standard of care may represent a safe and novel approach for the treatment in men with moderate to severe COVID-19.

Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04365127.

Funding Statement: The Institut Biochimique SA (IBSA, Lugano, Switzerland)

Declaration of Interests: SG, YM, SP, TK, DN, JH, SC, RIG, JM, CB, ML, VT report grants and nonfinancial support from Institut Biochimique SA (IBSA, Lugano, Switzerland), during the conduct of the study; SG,SP report patent pending on method of use of progesterone agonist for treatment of COVID-19 VT reports grants from NIH/NIAID ACTT (ACTT 1-3), outside the submitted work. DS, HG declare no competing interests.

Ethics Approval Statement: This study was approved by the Cedars-Sinai Institutional Review Board (IRB).

Suggested Citation

Ghandehari, Sara and Matusov, Yuri and Pepkowitz, Samuel and Stein, Donald and Kaderi, Tamana and Narayanan, Divya and Hwang, Josephine and Chang, Stephanie and Goodman, Robert and Ghandehari, Heli and Mirocha, James and Bresee, Catherine and Tapson, Victor and Lewis, Michael, Progesterone in Addition to Standard of Care Versus Standard of Care Alone in the Treatment of Men Admitted to the Hospital with Moderate to Severe COVID-19: A Randomised Control Phase 1 Trial. Available at SSRN: https://ssrn.com/abstract=3709835 or http://dx.doi.org/10.2139/ssrn.3709835

Sara Ghandehari (Contact Author)

Cedars Sinai Medical Center - Department of Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA
United States

Yuri Matusov

Cedars Sinai Medical Center - Department of Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA
United States

Samuel Pepkowitz

Cedars Sinai Medical Center - epartment of Pathology and Laboratory Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA 90048
United States

Donald Stein

Emory University - Department of Emergency Medicine ( email )

201 Dowman Drive
Atlanta, GA 30322
United States

Tamana Kaderi

Cedars Sinai Medical Center - Department of Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA
United States

Divya Narayanan

Cedars Sinai Medical Center - Department of Medicine

8700 Beverly Blvd.
Los Angeles, CA
United States

Josephine Hwang

Cedars Sinai Medical Center - Department of Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA
United States

Stephanie Chang

Cedars Sinai Medical Center - Department of Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA
United States

Robert Goodman

Cedars Sinai Medical Center - Department of Medicine

8700 Beverly Blvd.
Los Angeles, CA
United States

Heli Ghandehari

Independent ( email )

James Mirocha

Cedars Sinai Medical Center - Biostatistics Core ( email )

8700 Beverly Blvd.
Los Angeles, CA 90048
United States

Catherine Bresee

Cedars Sinai Medical Center - Biostatistics Core ( email )

8700 Beverly Blvd.
Los Angeles, CA 90048
United States

Victor Tapson

Cedars Sinai Medical Center - Department of Medicine ( email )

8700 Beverly Blvd.
Los Angeles, CA
United States

Michael Lewis

Cedars Sinai Medical Center - Department of Medicine

8700 Beverly Blvd.
Los Angeles, CA
United States

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