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

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.

Inclusion criteria

At least 18 years old Undergoing open-chest cardiac surgery With a history of SARS-CoV-2 infection Absence of respiratory infection-related symptoms or without the symptoms for more than 2 weeks Negative COVID-19 nucleic acid test result and without any sign of viral pneumonia based on a chest computed tomography (CT) scan on the day of randomization Exclusion criteria Emergent/urgent surgery, i.e., heart transplantation, surgeries for acute aortic dissection, et. al.

Renal insufficiency with estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73m2 Severe liver injury (Class C of Child-Pugh classification) Known allergy, intolerance, or contraindications to nirmatrelvir/ritonavir or ursodeoxycholic acid Having taken the following medications within the last 5 days (consideration for enrollment may be given if the patient's condition allows for a 5-day discontinuation period): alfuzosin, pethidine, piroxicam, propoxyphene, ranolazine, neratinib, venetoclax, amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone, quinidine, fusidic acid, voriconazole, astemizole, tefenadine, colchicine, rifabutin, rifampicin, lurasidone, clozapine, pimozide, quetiapine, ergot derivatives, cisapride, clorazepate, lovastatin, simvastatin, lomitapide, avanafil, sildenafil, vardenafil, diazepam, sulazepam, flurazepam, midazolam triazolam, carbamazepine, phenobarbital, and phenytoin