Molnupiravir and COVID-19 Mortality Reduction in the Omicron Era

NCT07720596 | Completed

• 1 other identifier: COVID-OMICRON-MPN-CFR
• Study Type: observational
• Target: 1,814,551
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective real-world target trial emulation uses complete Czech nationwide registry data to evaluate whether molnupiravir treatment is associated with lower COVID-19 mortality during the Omicron era. The study compares adults with confirmed acute COVID-19 treated with molnupiravir in addition to standard care versus matched controls treated with standard care without molnupiravir. Patients are followed for three months from time zero, and primary endpoints are the COVID-19 case fatality rate and all-cause mortality.

Conditions

COVID-19; SARS-CoV-2

Keywords

SARS-CoV-2 Infection; COVID-19; Omicron; pandemic; Molnupiravir; mortality; case fatality rate; CFR; risk factor; target trial emulation; real-world evidence

Outcome Measures

Primary Outcomes (2)

• COVID-19 CFR comparing patients treated with molnupiravir versus those not treated with molnupiravir.

  COVID-19 case fatality rate (CFR) comparing patients treated with molnupiravir in addition to standard care versus matched controls treated with standard care without molnupiravir among patients with acute COVID-19.

  Three months from time zero.

• ACM comparing patients treated with molnupiravir versus those not treated with molnupiravir.

  All-cause mortality (ACM) comparing patients treated with molnupiravir in addition to standard care versus matched controls treated with standard care without molnupiravir among patients with acute COVID-19.

  Three months from time zero.

Secondary Outcomes (4)

• CFR and ACM comparing outpatients treated with molnupiravir versus those not treated with molnupiravir.

  Three months from time zero.

• COVID-19 CFR and ACM comparing hospitalized patients treated with molnupiravir versus those not treated with molnupiravir.

  Three months from time zero.

• COVID-19 CFR and ACM comparing treatment with molnupiravir versus standard care alone among patients not receiving other targeted COVID-19 agents.

  Three months from time zero.

• COVID-19 CFR and ACM comparing treatment with molnupiravir versus standard care among patients receiving other targeted COVID-19 agents.

  Three months from time zero.

Other Outcomes (7)

• Healthy-user bias assessment: Number of health care contact episodes before SARS-CoV-2 positivity.

  One year preceding the patient's qualifying SARS-CoV-2 positivity.

• Healthy-user bias assessment: Number of hospitalization episodes before SARS-CoV-2 positivity.

  One year preceding the patient's qualifying SARS-CoV-2 positivity. Hospitalizations on the day of SARS-CoV-2 positivity are not counted, including hospitalizations that began before that day and were ongoing at the time of SARS-CoV-2 positivity.

• Healthy-user bias assessment: Number of hospitalization days before SARS-CoV-2 positivity.

  One year preceding the patient's qualifying SARS-CoV-2 positivity. Hospitalization days from a hospitalization that was ongoing on the day of SARS-CoV-2 positivity are not counted.

Study Arms (2)

Molnupiravir treatment in addition to standard care

Adults with confirmed COVID-19 who received molnupiravir in addition to standard care. Time zero is the date of molnupiravir treatment initiation proxied by dispensing.

Drug: Molnupiravir

Standard care without molnupiravir

Matched controls with confirmed COVID-19 who did not receive molnupiravir. Time zero is the matched date corresponding to the same number of days from positivity as the matched treated patient.

Interventions

Molnupiravir DRUG

800 mg of molnupiravir administered twice daily, i.e., four capsules every 12 hours for five days.

Also known as: Lagevrio, EIDD-2801

Molnupiravir treatment in addition to standard care

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All adult patients with confirmed SARS-CoV-2 infection recorded in Czech nationwide health registry data from January 1, 2022, through December 31, 2024.

You may qualify if:

• Adult infection episodes among patients aged 20 years or older.
• Confirmed acute SARS-CoV-2 positivity recorded in the Infectious Disease Information System (ISIN) during the Omicron-era study period.
• Eligible for analysis at time zero, defined as the date of molnupiravir dispensing for treated patients and the matched date for controls.
• Mild-to-moderate COVID-19 suitable for oral antiviral treatment, operationalized by excluding those already dead, in ICU, or receiving mechanical ventilation at time zero.

You may not qualify if:

• Age below 20 years at time of positivity.
• Death, ICU hospitalization, or mechanical ventilation at time zero.
• Receipt of molnupiravir, monoclonal antibodies, remdesivir, or nirmatrelvir/ritonavir within 14 days before positivity.
• Receipt of molnupiravir, monoclonal antibodies, remdesivir, or nirmatrelvir/ritonavir within 14 days after the qualifying SARS-CoV-2 positivity, but outside the treatment-initiation eligibility window according to the SmPC.

Sponsors & Collaborators

• Charles University, Czech Republic: lead
• Institute of Health Information and Statistics of the Czech Republic: collaborator

Study Sites (1)

Department of Pharmacology, Third Faculty of Medicine, Charles University

Prague, 10000, Czechia

Location

MeSH Terms

Conditions

COVID-19

Interventions

molnupiravir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Dalibor Veselý, M.D.

  Charles University, Prague, Third Faculty of Medicine

  PRINCIPAL INVESTIGATOR

• Jiří Slíva, M.D., Ph.D.

  Charles University, Prague, Third Faculty of Medicine

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: July 22, 2026
• Study Start: January 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Planned with manuscript publication as a public appendix.
• Access Criteria: Public appendix of a manuscript.

Locations

CZ (1)