Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients

Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients: A Randomized Placebo-Controlled Study

The goal of this randomized placebo-controlled study is to investigate the short-term effects of transdermal estrogen therapy on postmenopausal women with COVID-19 disease.

The main question[s] it aims to answer are:

• the clinical outcomes with adding estrogen treatment to conventional therapy of Covid-19 disease
• the biochemical outcomes with adding estrogen treatment to conventional therapy of Covid-19 disease

All participants received favipiravir for a week according to the national guidelines published by the Health Ministry of Turkish Republic at that time.

As an intervention, transdermal estradiol patch (7.8 mg patch/week) was applied for 14 days on the upper buttock of the patients in experimental arm. As a placebo, hydrogel patch (adhesive hydrogel patch/week) was applied to the female patients for 14 days.

Researchers compared experimental and control groups to see if the impact of adding estrogen on the clinical course of Covid-19 disease

Study Overview

• Status: Completed
• Conditions: COVID-19; Hormone Replacement Therapy
• Intervention / Treatment: Drug: Climara 0.1Mg/24Hr Transdermal System; Other: Hydrogel patch

Detailed Description

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, morbidity and mortality from Covid-19 disease were higher among men compared to women. This is caused by the differences in immunological response and viral pathogenesis between men and women. It is theoretically assumed that estrogen has a positive impact on female COVID-19 patients. In this randomized placebo-controlled study, we aimed to investigate the short-term effects of transdermal estrogen therapy on postmenopausal women with COVID-19 disease. Female patients diagnosed with Covid-19 disease were examined and only postmenopausal women were included into the study. The COVID-19 diagnosis was made with a positive reverse transcription-polymerase chain reaction (RT-PCR) test given with nasal and oral swabs. All participants received favipiravir for a week according to the national guidelines published by the Health Ministry of Turkish Republic at that time.

As an intervention, transdermal estradiol patch (7.8 mg patch/week) was applied for 14 days on the upper buttock of the patients in experimental arm. As a placebo, hydrogel patch (adhesive hydrogel patch/week) was applied to the female patients for 14 days.

Our primary outcome was to achieve better clinical and biochemical outcomes with adding estrogen treatment to conventional therapy of Covid-19 disease. The epidemiological and clinical data, the results of biochemical analysis, the information regarding the treatment and outcomes and serum estradiol levels were determined.

• Study Type: Interventional
• Enrollment (Actual): 9169
• Phase: Phase 2

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34098
    • Istanbul University-Cerrahpasa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female patients diagnosed with Covid-19 disease
• Postmenopausal women (who had 12 months of amenorrhea after their final menstrual period)
• Positive reverse transcription-polymerase chain reaction (RT-PCR) test given with nasal and oral swabs

Exclusion Criteria:

• Negative RT-PCR test
• Female patients at reproductive stage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; All patients were treated with favipiravir for a week. At the same time, the patients in this arm received Estradiol patch (Climara 7.8 mg patch/week, Bayer, Germany) for 14 days.	Drug: Climara 0.1Mg/24Hr Transdermal System; Transdermal estradiol patch is used.
Placebo Comparator: Placebo; All patients were treated with favipiravir for a week. At the same time, the patients in this arm received Hydrogel patch (Adhesive Hydrogel patch/week, Rebul Pharmacy, Turkey) for 14 days.	Other: Hydrogel patch; Adhesive Hydrogel patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of disease progression for mild cases	Proportion of patients who are hospitalised in 15 days	15 days
Evidence of disease progression for moderate and severe cases	Proportion of patients who required mechanical ventilation or died within 15 days	15 days
Kidney function tests	change of urea(mg/dL), creatinine(mg/dL) and uric acid (mg/dL) levels with estrogen and hydrogel patch application	15 days
Platelet	change of platelets in total blood count (*10^3/μL) with estrogen and hydrogel patch application	15 days
Markers of coagulation	change of fibrinogen (mg/dL) and D-dimer (mg/L) with estrogen and hydrogel patch application	15 days
Marker of inflammation	change of C-reactive protein (mg/L) levels within 15 days	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum E2 levels	change of serum E2 levels with estrogen and hydrogel patch application	15 days
rate of death	comparison of rate of death in each arm	15 days
rate of complications	comparison of rate of complications in each arm	15 days

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa (IUC)
• Collaborators: Turkish Menopause and Osteoporosis Society; Karakoy Rotary Club; Rebul Pharmacy
• Investigators: Principal Investigator: Cemal Tamer Erel, Prof, Istanbul University - Cerrahpasa (IUC)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Covid-19; hormone replacement therapy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 68871907-604.01.01-67414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No