Oestrogen Treatment for COVID-19 Symptoms

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

Detailed Description
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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 .

Official Title
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The Impact of Oestrogen Administration on Covid-19 Disease

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Transdermal estradiol gel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open label, randomized controlled trial, with patients randomized 1:1 to usual care, or usual care + oestrogen therapy. Prior to enrolment, an online CRF will be completed which will confirm that the patient meets the inclusion and exclusion criteria. Randomisation will be undertaken by the statistician in Qatar. Separate randomisation codes will be allocated for patients in Qatar and those in India, and separate randomisation will be performed for males and females. Randomisation will be enclosed in sequentially numbered sealed envelopes (with separate envelopes for males and females). Patients will be allocated to either the treatment or control group.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Oestrogen