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Estrogen Therapy in Non-severe COVID-19 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04539626
Recruitment Status : Active, not recruiting
First Posted : September 7, 2020
Last Update Posted : July 11, 2022
Sponsor:
Information provided by (Responsible Party):
Alfredo Cortés Algara, CMN "20 de Noviembre"

Tracking Information
First Submitted Date  ICMJE September 3, 2020
First Posted Date  ICMJE September 7, 2020
Last Update Posted Date July 11, 2022
Actual Study Start Date  ICMJE October 1, 2020
Actual Primary Completion Date July 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2020)
  • Clinical improve to estrogen therapy in non-severe COVID-19 patients Clinical improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 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 patients [ Time Frame: Day 14 ]
    • 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 patients [ Time Frame: Day 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2022)
  • Symptomatic improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 7 ]
    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.
  • Symptomatic improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 14 ]
    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.
  • Symptomatic improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 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 patients [ Time Frame: Day 7 ]
    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.
  • Biochemical improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 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 patients [ Time Frame: Day 21 ]
    Percentage change from Angiotensin 1-7, measured with the Human Angiotensin 1-7 ELISA kit (colorimetric) [pg/mL]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2020)
  • Symptomatic improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 7 ]
    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.
  • Symptomatic improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 14 ]
    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.
  • Symptomatic improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 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 patients [ Time Frame: Day 7 ]
    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.
  • Biochemical improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 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.
  • Biochemical improve to estrogen therapy in non-severe COVID-19 patients [ Time Frame: Day 21 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Estrogen Therapy in Non-severe COVID-19 Patients
Official Title  ICMJE Estrogen Therapy in Non-severe COVID-19 Patients: Proposed Treatment Scheme in a Tertiary Hospital
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
The Outcome Assessor will be an external member of the Gynecology Service, which will be blinded to the intervention.
Primary Purpose: Treatment
Condition  ICMJE Covid-19
Intervention  ICMJE Drug: Estrogen Therapy
EVRA skin patches with norelgesetromin 6mg / ethinyl estradiol 0.60mg, (1 patch will be placed every week during 21 days)
Other Names:
  • Norelgesetromin
  • Ethinyl estradiol
Study Arms  ICMJE
  • Experimental: Estrogen Therapy

    Drug: 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)

    Intervention: Drug: Estrogen Therapy
  • No Intervention: Control Group
    Patients who will receive conventional COVID-19 treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 27, 2022)
44
Original Estimated Enrollment  ICMJE
 (submitted: September 3, 2020)
60
Estimated Study Completion Date  ICMJE December 2022
Actual Primary Completion Date July 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04539626
Other Study ID Numbers  ICMJE 03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Alfredo Cortés Algara, CMN "20 de Noviembre"
Original Responsible Party Same as current
Current Study Sponsor  ICMJE CMN "20 de Noviembre"
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Rodrigo Ruz Barros, MD CMN "20 de Noviembre"
Study Chair: Daniel Santillán Cortés, MSc CMN "20 de Noviembre"
Study Chair: Mónica Escamilla Tilch, PhD CMN "20 de Noviembre"
Study Chair: Juan A Pineda Juárez, PhD CMN "20 de Noviembre"
Study Chair: Sandra Muñoz López, MD CMN "20 de Noviembre"
Study Chair: Maricela Escarela Serrano, MD CMN "20 de Noviembre"
Study Chair: Paul Mondragón Terán, PhD CMN "20 de Noviembre"
Study Chair: Alberto H De la Vega Bravo, MD CMN "20 de Noviembre"
Principal Investigator: Alfredo L Cortés Algara, MD, MSc CMN "20 de Noviembre"
Study Chair: Samuel Reyes-Long, MSc Neurociencias básicas, Instituto Nacional de Rehabilitación LGII
Study Chair: Cindy Bandala, MD MSc PhD Neurociencias básicas, Instituto Nacional de Rehabilitación LGII; Escuela Superior de Medicina, Instituto Politécnico Nacional
PRS Account CMN "20 de Noviembre"
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP