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Estrogen Therapy in Non-severe COVID-19 Patients

Not Applicable
Active, not recruiting
Conditions
Covid-19
Interventions
Drug: Estrogen Therapy
Registration Number
NCT04539626
Lead Sponsor
CMN "20 de Noviembre"
Brief Summary

The primary objective of this study is to evaluate the effect of additional estradiol estrogen therapy on clinical response and mortality in non-severe COVID-19 patients

Detailed Description

Actually, there is not treatment or vaccine that can prevent or control the evolution of COVID-19. The epidemiological data reported in China by the Center for Disease Control (CDC) on February 2020, reported that 87% of the patients have been adults in an age range of 30-69 years. In addition, different studies have shown that male gender are more vulnerable for the contagion of the virus (60%-80%), as well as the clinical evolution of COVID-19 (including mortality) compared to the female sex (20-40%), independently of individual such as diabetes, cardiovascular diseases, obesity, mainly.

The mechanism of SARS-CoV-2 infection has been shown to occur with the interaction of angiotensin converting enzyme 2 (ACE2), this enzyme is expressed in lungs, brain, heart, kidneys and gastrointestinal tract. Also, has been shown that older people have higher levels of ACE2 expression. Among the different molecular functions of ACE2 are the regulation of cell proliferation, cytokine production, and inflammatory response.

It has been proposed that exogenous human recombinant ACE2 could be an alternative treatment for COVID-19, however, this treatment is not yet highly available and could entail high costs. Other molecules as estrogens have been proposed in different research groups, for its capacity to increase the gene expression of ACE2/Ang 1-7. This mechanism could reduce lung and endothelial damage and coagulopathy in COVID-19 patients.

So, it is relevant to evaluate the effect of additional estradiol estrogen (as adjuvant therapeutic element) therapy on clinical response and mortality in non-severe COVID-19 patients.

A controlled clinical trial will be conducted in a tertiary hospital in Mexico City, Mexico. Participants will be divide in two groups; 1) intervention: who will receive EVRA skin patches (1 patch every week during 21 days) with norelgesetromin 6mg / ethinyl estradiol 0.60mg and 2) control: who will receive conventional treatment

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
44
Inclusion Criteria
  • Male ≥ 18 years of age and female ≥ 55 years of age

  • Diagnosis of positive SARS-CoV-2 infection confirmed by clinical diagnosis and / or RT-PCR test

  • Hospitalized patients in acute disease* stages of the disease

  • Agree to participate in the study prior to signing an informed consent.

  • Patients with conventional treatment with anticoagulants (Noxaparin)

    • Acute disease: patients who are hospitalized, conscious, not intubated, with biochemical values of D-Dimer> 2, Ferritin> 1000 u.
Exclusion Criteria
  • Patients with abnormal genital bleeding
  • Patients with protein C or protein S deficiency
  • Patients with liver failure (cirrhosis, hepatitis C)
  • Patients with history of allergic reaction to estrogens use
  • Patients receiving lamotrigine therapy
  • Patients with a history of breast cancer and / or endometrial cancer
  • Patients with severe hypoxia at risk of acute intubation in ED
  • Patients with a history of cerebrovascular history
  • Male patients with testosterone treatment
  • Patients with a history of myocardial infarction, who have cardiac stents and / or unstable angina pectoris
  • Patients with previous hormonal treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Estrogen TherapyEstrogen TherapyDrug: Norelgesetromin 6mg / Ethinyl estradiol 0.60mg Dosage form: EVRA skin patches with norelgesetromin 6mg / ethinyl estradiol 0.60mg, (1 patch will be placed every week during 21 days)
Primary Outcome Measures
NameTimeMethod
Clinical improve to estrogen therapy in non-severe COVID-19 patients Clinical improve to estrogen therapy in non-severe COVID-19 patientsDay 7

* Success rate in reducing hospitalization days

* Success rate in no oxygen therapy use (low or high-flow oxygen)

* Success rate in no intubation and/or mechanical ventilation

* Success rate in non mortality occurrence

Clinical improve to estrogen therapy in non-severe COVID-19 patientsDay 21

* Success rate in reducing hospitalization days

* Success rate in no oxygen therapy use (low or high-flow oxygen)

* Success rate in no intubation and/or mechanical ventilation

* Success rate in non mortality occurrence

Secondary Outcome Measures
NameTimeMethod
Symptomatic improve to estrogen therapy in non-severe COVID-19 patientsDay 21

According to the National Committee for Epidemiological Surveillance (CONAVE) in Mexico, COVID-19 symptomatic onset rate defined as the presence of cough, fever or headache during the last 7 days, accompanied at least one of the following symptoms: dyspnea, arthralgia, myalgia, odynophagia / pharyngeal burning, rhinorrhea, conjunctivitis or chest pain.

Biochemical improve to estrogen therapy in non-severe COVID-19 patientsDay 14

Percentage change from hemoglobin, hematocrit, leukocytes, erythrocytes, platelets, prothrombin, partial thromboplastin activation time, anti-thrombin activity, fibrinogen, fibrin degradation products, D-Dimer, ALT, AST, ALP, GGT, LD, albumin, cholesterol, triglycerides, HDL, LDL, C-reactive protein, estrogens and progesterone levels, pro inflammatory cytokine and nitric oxide profile.

Angiotensin 1-7 change after estrogen therapy in non-severe COVID-19 patientsCOVID-19 patientsDay 21

Percentage change from Angiotensin 1-7, measured with the Human Angiotensin 1-7 ELISA kit (colorimetric) \[pg/mL\]

Trial Locations

Locations (1)

CMN "20 de Noviembre"

🇲🇽

Mexico City, Benito Juárez, Mexico

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