Pericardiotomy in Cardiac Surgery (PRINCE)

Pericardiotomy in Cardiac Surgery Trial

PRINCE is an international, multicentre, randomized controlled trial of posterior pericardiotomy in patients without a history of atrial fibrillation (AF) or flutter undergoing cardiac surgery.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Atrial Flutter; Cardiac Events
• Intervention / Treatment: Procedure: Left Posterior Pericardiotomy

Detailed Description

Approximately 30% of cardiac surgical patients develop post-operative atrial fibrillation (POAF). Its incidence varies depending on the type of cardiac operation. POAF is associated with short- and long-term adverse events, including mortality, stroke, and heart failure. POAF has also been significantly associated with unplanned hospitalization for heart failure.

During cardiac surgery, pericardial fluid tends to collect posterior to the left atrium. Even small amounts of fluid may trigger atrial arrhythmias. A posterior left pericardiotomy is a surgical procedure that involves cauterizing an opening between the left inferior pulmonary vein and the diaphragm. This procedure may allow for more prolonged drainage of the pericardial fluid into the left pleural space. Recent research evidence found that posterior pericardiotomy was associated with a significantly lower incidence of POAF.

The existing data on posterior pericardiotomy is promising for a reduction in POAF. However, no high-quality study has demonstrated that this reduction improves clinical outcomes in the years after cardiac surgery. The PRINCE trial's long-term follow-up of patients randomized to left posterior pericardiotomy could conclusively demonstrate whether the relationship of POAF to post-discharge clinical outcomes is causal and modifiable.

The PRINCE trial will evaluate the effectiveness and safety of posterior left pericardiotomy in preventing POAF and improving post-discharge clinical outcomes in a broad spectrum of cardiac surgery patients.

The intervention under investigation is left posterior pericardiotomy which is compared to no posterior pericardiotomy during cardiac surgery. The early co-primary outcome is in-hospital POAF, and the late co-primary outcome is the hierarchical composite of time to all-cause death, time to ischemic stroke, time to systemic arterial embolism, time to unplanned hospital visit/readmission for cardiac reasons, and time to atrial fibrillation after index hospital discharge.

The study will enrol 1400 patients from 30 centres, globally. Follow-up visits will be performed in person or by telephone 1 and 6 months post-randomization (+7 days), and then every 6 months (+30 days) until an average follow-up of 5 years for the study participants (estimated to be 4 years after completion of enrolment).

• Study Type: Interventional
• Enrollment (Estimated): 1400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Richard Whitlock; Phone Number: 40306 9055274322; Email: Richard.Whitlock@phri.ca
• Study Contact Backup: Name: PRINCE Coordinators; Email: PRINCE@phri.ca

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University Vienna
    • Contact: Dr. Sigrid Sandner, MD; Phone Number: +43 (0)1 40400-69895; Email: sigrid.sandner@meduniwien.ac.at
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Emilie Belley-Côté, MD, PhD, FRCPC; Phone Number: 41147 (905) 527-4322; Email: Emilie.Belley-Cote@phri.ca
• Italy
  • Foggia, Italy, 71122
    • Recruiting
    • University of Foggia, Policlinico Foggia
    • Contact: Prof. Domenico Paparella, MD, PHD; Phone Number: +39 0881 736145; Email: domenico.paparella@unifg.it
• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Dr. Mario Gaudino, MD, PhD; Phone Number: 212-746-1815; Email: mfg9004@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients greater than or equal to 18 years of age
• Requiring surgical intervention on the proximal aorta, cardiac valves, and/or coronary arteries
• Able to provide informed consent

Exclusion Criteria:

• History of atrial fibrillation or flutter
• Cardiac surgery procedures not included in the inclusion criteria (planned ventricular assistance device, aortic arch, transplantation surgery)
• Prior cardiac surgery requiring opening of the pericardium
• Previous surgical instrumentation of the left pleural cavity
• Patient undergoing minimally invasive cardiac surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Left Posterior Pericardiotomy Group; The surgeon will perform a left posterior pericardiotomy during the patient's cardiac surgery.	Procedure: Left Posterior Pericardiotomy; The surgeon will perform a left posterior pericardiotomy while the patient is on cardiopulmonary bypass. A soft channel drain will be put into place at an angle directed toward the posterior pericardium. The surgeon will grasp the pericardium and use cautery to make a 4- to 5-cm opening between the left inferior pulmonary vein and the diaphragm. The previously prepared channel drain is cut to the desired length and placed through the pericardiotomy along the diaphragm and into the pleural space.
No Intervention: No Posterior Pericardiotomy Group; The surgeon will not perform a posterior pericardiotomy during the patient's cardiac surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical composite of all-cause death, ischemic stroke, systemic arterial embolism, unplanned hospital visit/readmission for cardiac reasons, and atrial fibrillation.	Number of patients with a composite of all-cause death, ischemic stroke, systemic arterial embolism, unplanned hospital visit/readmission for cardiac reasons, and atrial fibrillation events, evaluated using the win ratio (thereby accounting for the difference in importance of these outcomes).	Over the duration of the follow-up period to a common end date (mean follow-up of 5 years).
In-hospital post-operative atrial fibrillation	Number of patients with post-operative atrial fibrillation within the first 5 days postoperatively or up to hospital discharge, whichever occurs first	Within 5 days after index cardiac surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative atrial fibrillation (POAF)	Number of patients with post-operative atrial fibrillation	Over the duration of the follow-up period to a common end date (mean follow-up of 5 years).
Length of post-operative in-hospital stay	Length of time the patient in hospital after their index cardiac surgery	Over the duration of the follow-up period to a common end date (mean follow-up of 5 years).
Pericardial effusion without tamponade	Number of pericardial effusions that occur, excluding cardiac tamponade	From index surgery completion to within 30 days of index surgery
Death	Occurrence of death	From index surgery completion to within 30 days of index surgery
Ischemic stroke or systemic arterial embolism	Number of ischemic strokes or systemic arterial embolisms	From index surgery completion to within 30 days of index surgery
Hospital readmission or unplanned hospital visit	Number of hospital readmissions or unplanned hospital visits	From index surgery completion to within 30 days of index surgery
Quality of life assessed by the European quality of life index version 5D (EQ-5D-5L) questionnaire	The EQ-5D-5L consists of a descriptive system and the EQ visual analogue scale (EQ VAS) scale of 0-100 where the endpoints are labelled 'The best health you can image' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is measured on a 5 point scale: no problems, slight problems, moderate problems, severe problems and extreme problems.	Over the duration of the follow-up (mean follow-up of 5 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with phrenic nerve injuries	Safety outcome	Within 30 days of index surgery
Number of patients with left pleural interventions	Safety outcome	Within 30 days of index surgery
Number of patients with esophageal injuries	Safety outcome	Within 30 days of index surgery
Number of patients requiring re-operation for bleeding	Safety outcome	Within 48 hours of index surgery completion
Number of patients with cardiac tamponade	Safety outcome	Within 30 days of index surgery

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Weill Medical College of Cornell University; McMaster University; Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Richard Whitlock, Population Health Research Institute; Principal Investigator: Emilie Belley-Côté, Population Health Research Institute; Principal Investigator: Mario Gaudino, Weill Medical College of Cornell University; Principal Investigator: Sigrid Sandner, Medical University Vienna; Principal Investigator: Björn Redfors, Göteborg University

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Hospital Readmission; Pericardiotomy; Post-Operative Atrial Fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Cardiovascular Diseases; Atrial Fibrillation; Atrial Flutter
• Other Study ID Numbers: PRINCE - 2024

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