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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Cardiac Surgery

Intervention / Treatment
-----------------
* Drug: Nirmatrelvir/ritonavir
* Drug: Ursodeoxycholic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 |