We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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"

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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

Condition or disease Intervention/treatment Phase
Covid-19 Drug: Estrogen Therapy Not Applicable

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
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
Official Title: Estrogen Therapy in Non-severe COVID-19 Patients: Proposed Treatment Scheme in a Tertiary Hospital
Actual Study Start Date : October 1, 2020
Actual Primary Completion Date : July 30, 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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)

 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
No Intervention: Control Group
Patients who will receive conventional COVID-19 treatment


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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]


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04539626


Locations
Layout table for location information
Mexico
CMN "20 de Noviembre"
Mexico City, Benito Juárez, Mexico, 03100
Sponsors and Collaborators
CMN "20 de Noviembre"
Investigators
Layout table for investigator information
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
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Alfredo Cortés Algara, Gynecology Service Member, MD, MSc, CMN "20 de Noviembre"
ClinicalTrials.gov Identifier: NCT04539626    
Other Study ID Numbers: 03
First Posted: September 7, 2020    Key Record Dates
Last Update Posted: July 11, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alfredo Cortés Algara, CMN "20 de Noviembre":
COVID-19
Estrogens
Severe Acute Respiratory Syndrome Coronavirus-2
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
 Ethinyl Estradiol
Estradiol
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents, Hormonal
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Contraceptives, Oral, Hormonal
Contraceptives, Oral