Prophylactic Effect of Nirmatrelvir/Ritonavir and Ursodeoxycholic Acid on Reducing Complications After Cardiac Surgery (PEP)

Prophylactic Effect of Nirmatrelvir/Ritonavir and Ursodeoxycholic Acid on Reducing Complications After Cardiac Surgery During COVID-19 Pandemics: A Prospective, Randomized Controlled, Multicenter Trial

Prophylactic effect of nirmatrelvir/ritonavir and ursodeoxycholic acid on reducing complications after cardiac surgery during covid-19 pandemics (the pep trial) is a multicenter, randomized controlled trial. The aim of the pep trial is to investigate whether prophylactic use of nirmatrelvir/ritonavir and ursodeoxycholic could reduce complications after cardiac surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiac Surgery
• Intervention / Treatment: Drug: Nirmatrelvir/ritonavir; Drug: Ursodeoxycholic acid

Detailed Description

After informed consent, four centers and 436 eligible admissions will be recruited. Eligible patients would be randomized (1:1:1:1) to nirmatrelvir/ritonavir group (nirmatrelvir 300mg q12h and ritonavir 100 mg q12h for 5 days), ursodeoxycholic acid group (ursodeoxycholic acid group, 15mg/kg/day bid for5 days), combination group (nirmatrelvir/ritonavir and ursodeoxycholic acid for 5days) and control group.

• Study Type: Interventional
• Enrollment (Actual): 491
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 10010
      • Fuwai Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• COVID-19 nucleic acid test or antigen test positive history, without symptom or recover from COVID-19 related symptoms ≥2 weeks
• Receive open-chest cardiac surgery
• COVID-19 nucleic acid test and antigen test negative and no signs of pneumonia in chest CT
• Patients with written informed consent.

Exclusion Criteria:

• Emergency surgery
• eGFR ≤30ml/min
• Severe liver dysfunction
• Contraindication to nirmatrelvir/ritonavir or ursodeoxycholic acid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group; No intervention
Experimental: NR group; nirmatrelvir 300mg q12h and ritonavir 100 mg q12h for 5 days	Drug: Nirmatrelvir/ritonavir; nirmatrelvir 300mg q12h and ritonavir 100 mg q12h for 5 days
Experimental: UA group; ursodeoxycholic acid group, 15mg/kg/day bid for5 days	Drug: Ursodeoxycholic acid; ursodeoxycholic acid 15mg/kg/day bid for5 days
Experimental: combination group; nirmatrelvir 300mg q12h and ritonavir 100 mg q12h for 5 days and ursodeoxycholic acid group, 15mg/kg/day bid for5 days	Drug: Nirmatrelvir/ritonavir; nirmatrelvir 300mg q12h and ritonavir 100 mg q12h for 5 days; Drug: Ursodeoxycholic acid; ursodeoxycholic acid 15mg/kg/day bid for5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACCE	All-cause mortality, myocardial infarction, stroke, moderate to severe acute kidney injury, and COVID-19 pneumonia	30 days after surgery or during hospitalization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality	30 days after surgery or during hospitalization
Rate of Myocardial infarction	new onset of myocardial infarction	30 days after surgery or during hospitalization
Rate of Stroke	new onset of stroke	30 days after surgery or during hospitalization
Rate of Moderate to severe acute kidney injury	new onset of moderate to severe acute kidney injury	30 days after surgery or during hospitalization
Rate of COVID-19 pneumonia	new onset of COVID-19 pneumonia	30 days after surgery or during hospitalization
Rate of Cardiogenic death	Cardiogenic death	30 days after surgery or during hospitalization
Rate of Severe pneumonia	new onset of Severe pneumonia	30 days after surgery or during hospitalization
Rate of Ventilation ≥24h	Ventilation ≥24h after surgery	30 days after surgery or during hospitalization
Rate of Pulmonary embolism	new onset of Pulmonary embolism	30 days after surgery or during hospitalization
Rate of Re-operation for bleeding	Re-operation for bleeding after primary surgery	30 days after surgery or during hospitalization
All-cause mortality	All-cause mortality	1 year after surgery
Rate of Myocardial infarction	new onset of Myocardial infarction	1 year after surgery
Rate of Stroke	new onset of Stroke	1 year after surgery
Rate of Renal insufficiency	new onset of Renal insufficiency	1 year after surgery
Rate of Re-hospitalization for respiratory disease	Re-hospitalization for respiratory disease	1 year after surgery
Rate of Cardiogenic re-hospitalization	Cardiogenic re-hospitalization	1 year after surgery

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Investigators: Principal Investigator: Shengshou Hu, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2023
• Primary Completion (Actual): March 24, 2023
• Study Completion (Anticipated): January 6, 2026

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Gastrointestinal Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Cholagogues and Choleretics; Ritonavir; Ursodeoxycholic Acid
• Other Study ID Numbers: NCRC2023001

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