Clinical trial NCT04853069: Oestrogen Treatment for COVID-19 Symptoms
Official title: The Impact of Oestrogen Administration on Covid-19 Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
Oestrogen
Lead sponsor: Hamad Medical Corporation
Sponsor class: INDUSTRY
Collaborators: name: Laboratoires Besins International
First posted: 2021-04-21
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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

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

.

Eligibility criteria: 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

Primary outcomes:
measure: Evidence of disease progression for mild cases
timeFrame: 28 days
measure: Evidence of disease progression in hospitalised patients (moderate and severe cases)
timeFrame: 28 days
Secondary outcomes:
measure: Hospital mortality
timeFrame: 28 days
measure: Duration of hospital admission
timeFrame: 28 days
measure: Admission to ICU/ HDU facility
timeFrame: 28 days
measure: Need for renal replacement therapy
timeFrame: 28 days
measure: Ventilation
timeFrame: 28 days
measure: Time to being fit for hospital discharge
timeFrame: 28 days
Other outcomes:
Locations:
city: Doha
country: Qatar
facility: Hamad Medical Corporation
Study officials:
References: