COVID-19
Conditions
Keywords
COVID-19, Oestrogen
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 .
Interventions
Patients will receive standard care +/- (randomsed 1:1) transdermal 17ß-estradiol gel (3 mg; applied to forearm, upper arm and shoulder) for ten days.
Sponsors
Laboratoires Besins International
Hamad Medical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evidence of disease progression for mild cases | 28 days | Proportion hospitalised within 28 days |
| Evidence of disease progression in hospitalised patients (moderate and severe cases) | 28 days | Proportion requiring mechanical ventilation or dying within 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of hospital admission | 28 days | Length of stay at hospital |
| Admission to ICU/ HDU facility | 28 days | Length of stay at ICU/HDU facility |
| Time to being fit for hospital discharge | 28 days | Time of discharge |
| Ventilation | 28 days | Proportion requiring mechanical ventilation within 28 days |
| Need for renal replacement therapy | 28 days | Proportion requiring renal replacement therapy |
| Hospital mortality | 28 days | Rate of mortality |
Countries
Qatar
Contacts
Primary ContactMichael P Frenneaux
Backup ContactAdel Ganaw
Outcome results
None listed