Clinical trial NCT04539626: Estrogen Therapy in Non-severe COVID-19 Patients
Official title: Estrogen Therapy in Non-severe COVID-19 Patients: Proposed Treatment Scheme in a Tertiary Hospital
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Covid-19
Keywords: COVID-19
Estrogens
Severe Acute Respiratory Syndrome Coronavirus-2
Lead sponsor: CMN "20 de Noviembre"
Sponsor class: OTHER
First posted: 2020-09-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Clinical improve to estrogen therapy in non-severe COVID-19 patients Clinical improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 7
measure: Clinical improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 14
measure: Clinical improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 21
Secondary outcomes:
measure: Symptomatic improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 7
measure: Symptomatic improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 14
measure: Symptomatic improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 21
measure: Biochemical improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 7
measure: Biochemical improve to estrogen therapy in non-severe COVID-19 patients
timeFrame: Day 14
measure: Angiotensin 1-7 change after estrogen therapy in non-severe COVID-19 patientsCOVID-19 patients
timeFrame: Day 21
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: CMN "20 de Noviembre"
state: Benito Juárez
Study officials:
affiliation: CMN "20 de Noviembre"
name: Rodrigo Ruz Barros, MD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Daniel Santillán Cortés, MSc
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Mónica Escamilla Tilch, PhD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Juan A Pineda Juárez, PhD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Sandra Muñoz López, MD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Maricela Escarela Serrano, MD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Paul Mondragón Terán, PhD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Alberto H De la Vega Bravo, MD
role: STUDY_CHAIR
affiliation: CMN "20 de Noviembre"
name: Alfredo L Cortés Algara, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurociencias básicas, Instituto Nacional de Rehabilitación LGII
name: Samuel Reyes-Long, MSc
role: STUDY_CHAIR
affiliation: Neurociencias básicas, Instituto Nacional de Rehabilitación LGII; Escuela Superior de Medicina, Instituto Politécnico Nacional
name: Cindy Bandala, MD MSc PhD
role: STUDY_CHAIR
References: