Ignite Creation Date:
2024-05-06 @ 4:05 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04865029
Status:
TERMINATED
Last Update Posted:
2023-06-27
First Post:
2021-04-21
Brief Title:
Estradiol and Progesterone in Hospitalized COVID-19 Patients
Sponsor:
Tulane University
Organization:
Tulane University
Study Overview
Official Title:
Acute Estradiol and Progesterone Therapy in Hospitalized Adults to Reduce Coronavirus Disease COVID-19 Severity A Randomized Control Trial
Status:
TERMINATED
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of enrollment due to change of COVID 19 variant prevalence
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine to what extent a short systemic steroid therapy with estradiol and progesterone administered early to hospitalized and confirmed COVID-19 positive patients of both sexes in addition to standard of care SOC can reduce the severity of symptoms and outcomes compared to SOC alone
Detailed Description:
Severe Acute Respiratory Syndrome Associated Corona Virus SARS-CoV-2 causing COVID-19 has killed over 28 million people globally including 550000 in the US as of March 2021 Although the vaccination campaign is ramping up vaccination hesitancy in the United States represents up to 25-30 of the population and hospitalizations and deaths are still at the level of 2020 Apart from corticosteroids most available therapeutic options are at best marginally efficient in reducing disease severity and mortality and extremely expensive Therefore the systematic investigation of clinically approved drugs is a priority in order to determine what does improve the disease and invest resources to go to full-scale production Our current understanding of the disease is that COVID-19 deaths result from an inappropriate immune response with outpouring of pro-inflammatory chemokines leading to lung infiltration and hyperactivation of monocytes and macrophages producing pro-inflammatory cytokines cytokine storm resulting in lung edema reduced gas exchange and ultimately leading to acute respiratory distress syndrome and multiorgan failure Men with COVID-19 have a uniformly more severe outcome than women In series from China Europe and the US COVID-19 mortality was consistently 15 to 2-fold higher in men than in women suggesting that female biological sex is protecting women from COVID-19 mortality It is established that women exhibit heightened immune responses to viral infections compared to men which is at least partially due to the genetic benefit of gene dosage in X-linked immune-response genes Ovarian steroids however also play a protective role In New York City among 5700 hospitalized patients the female protection from COVID-19 mortality was observed at all ages but was more pronounced in subjects under 50 years of age 18 mortality in women compared to patients 50 years of age 405 mortality in women suggesting that ovarian steroids are involved in mitigating COVID-19 mortality in pre-menopausal women Further the analysis of electronic health records of over 68000 COVID-19 patients revealed that estrogen therapy is associated with more than 50 reduction in mortality The main female steroids 17β-estradiol and progesterone exhibit potent immuno-modulatory and anti-inflammatory actions via estrogen and progesterone receptors expressed in all immune cells including epithelial cells macrophages dendritic cells cluster of differentiation 4 CD4 and cluster of differentiation 8 CD8 lymphocytes and B cells Progesterone also acts partially via the glucocorticoid receptor Together estradiol and progesterone produce a state of decreased innate immune cells production of proinflammatory cytokines enhanced T cells anti-inflammatory responses and immune tolerance and enhanced B-cell-mediated antibody production The National Institutes of Health NIH COVID-19 Treatment Guidelines Panel recommends the use of dexamethasone 6 mg per day for up to 10 days or until hospital Discharge whichever comes first as standard of care SOC for the treatment of hospitalized COVID-19 patients who require supplemental oxygen but who are not mechanically ventilated and for the treatment of hospitalized patients who are mechanically ventilated Remdesivir is SOC at Tulane for COVID-19 patients who require supplemental oxygen but who are not mechanically ventilated We believe that in hospitalized COVID-19 patients a short treatment with the combination estradiol and progesterone administered early and as a prevention in addition to SOC will prevent or mitigate the cytokine storm while increasing antibody production and prevent severe outcomes without side effects Therefore it will provide steroid immunomodulation without immunosuppression The advantage of repurposing estradiol and progesterone compounds is the depth of knowledge regarding their clinical efficacy and toxicity that has accumulated from decades of clinical and basic studies Estradiol and progesterone are widely available in hospitals inexpensive manufacturable to scale and can be prescribed immediately
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None