Oestrogen Treatment for COVID-19 Symptoms

The Impact of Oestrogen Administration on Covid-19 Disease

The aim of this trial is to determine whether oestrogen treatment mitigates disease progression and severity in confirmed COVID19.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Transdermal estradiol gel

Detailed Description

It is known that (i) women are relatively protected from the impacts of other respiratory viruses, and that oestrogen may partly mediate this effect (ii) Oestrogen protects rodents from SARS-CoV-1 related mortality (iii) Women are relatively protected from developing or dying from severe COVID-19 and (iv) Postmenopausal women taking oestrogen replacement appear less likely to suffer Covid19-related critical illness. These effects may be mediated through oestrogen-related immunomodulation. In addition, however, 17β estradiol reduces expression of ACE2 (the receptor protein through which SARS-CoV-2 gains cellular entry) in tissues such as the kidney. As such, supplemental oestrogen may represent an effective therapy for Covid19.

We will randomise adult men and postmenopausal women with confirmed Covid19 disease to receive 10 days of transdermal oestrogen (3mg/day). The primary endpoint will be evidence of disease progression, indicated by hospitalisation (mild cases) or need for mechanical ventilation or death within 28 days of randomisation for those hospiatlsied. Secondary outcomes will include hospital mortality, duration of hospital admission, admission to ICU/ HDU facility, ICU/ HDU length of stay, need for renal replacement therapy, receipt and duration of invasive mechanical ventilation, cause-specific mortality and time to being fit for hospital discharge

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• Study Type: Interventional
• Enrollment (Anticipated): 2000
• Phase: Phase 2

Contacts and Locations

Study Locations

• Qatar
  • Doha, Qatar, PO Box 3050
    • Hamad Medical Corporation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute Covid-19 disease (PCR-confirmed or clinically diagnosed with high certainty)
• Adult males > 18 years of age OR
• Post-menopausal women (spontaneous amenorrhoea for >12 months in the absence of any other cause)

Exclusion Criteria:

Women:

• taking oestrogen supplements or oestrogen receptor antagonists
• with abnormal genital bleeding
• with a history of breast cancer
• with a history of endometrial or ovarian cancer
• with untreated endometrial hyperplasia

Men:

• taking hormone therapies (e.g. for prostate cancer)

Any subject:

• failure to obtain consent
• taking lamotrigine
• with a thromboembolic disorder (e.g. Protein C or Protein S deficiency, antithrombin III deficiency)
• with pre-existing liver or renal disease
• with known allergy to exogenous oestrogens
• with a history of porphyria
• with a history of thromboembolic event including deep vein thrombosis, thromboembolic stroke or pulmonary emboli
• taking part in another interventional clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oestrogen Therapy; Patients will receive standard care + transdermal 17ß-estradiol gel (3 mg) for ten days.	Drug: Transdermal estradiol gel; Patients will receive standard care +/- (randomsed 1:1) transdermal 17ß-estradiol gel (3 mg; applied to forearm, upper arm and shoulder) for ten days.; Other Names: oestrogel; estrogel
No Intervention: Control Group; Patients will receive only standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of disease progression for mild cases	Proportion hospitalised within 28 days	28 days
Evidence of disease progression in hospitalised patients (moderate and severe cases)	Proportion requiring mechanical ventilation or dying within 28 days	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital mortality	Rate of mortality	28 days
Duration of hospital admission	Length of stay at hospital	28 days
Admission to ICU/ HDU facility	Length of stay at ICU/HDU facility	28 days
Need for renal replacement therapy	Proportion requiring renal replacement therapy	28 days
Ventilation	Proportion requiring mechanical ventilation within 28 days	28 days
Time to being fit for hospital discharge	Time of discharge	28 days

Collaborators and Investigators

• Sponsor: Hamad Medical Corporation
• Collaborators: Laboratoires Besins International

Study record dates

Study Major Dates

• Study Start (Anticipated): May 17, 2021
• Primary Completion (Anticipated): February 28, 2022
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 21, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Oestrogen
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: MRC-05-099

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No