CPPF After General Cardiac Surgery (FLUID)

Continuous Postoperative Pericardial Flushing After General Cardiac Surgery Procedures With the Haermonics Investigational Device: Study Protocol of the FLUID (FLUsh With Investigational Device) Trial

In two randomized clinical trials the investigators have demonstrated that continuous postoperative pericardial flushing (CPPF) therapy can reduce postoperative blood loss and bleeding-related complications after cardiac surgery and that CPPF therapy is safe and feasible in an experimental setting. The Haermonics investigational device is a novel medical device that enables CPPF therapy to be used in daily clinical setting. The aim of this study is three-fold. First, to evaluate the safety and functionality of the Haermonics investigational device. Secondly, to investigate the effect of CPPF therapy on bleeding related complications in the adulty cardiac surgery population. Thirdly, to explore the effect of CPPF therapy on intraluminal chest tube clogging.

Study Overview

• Status: Terminated
• Conditions: Postoperative Hemorrhage; Cardiac Tamponade; Cardiac Surgical Procedures; Retained Blood Syndrome
• Intervention / Treatment: Device: CPPF

Detailed Description

CPPF therapy

Prolonged or excessive bleeding after cardiac surgery can lead to a broad spectrum of secondary complications. One of the underlying causes is incomplete wound drainage, with subsequent accumulation of blood and clots in the pericardium. It has been demonstrated that this retained blood and clots lead to even more fibrinolytic activity in the mediastinum and pericardial space, and therefore may contribute to increased or prolonged bleeding. Based on this principle, the method of continuous postoperative pericardial flushing (CPPF) has been invented and further developed. The hypothesis is that CPPF therapy works by mechanical cleaning properties and by diminishing fibrinolysis and inflammation. The CPPF protocol includes the inflow of NaCl 0,9% flushing fluid into the pericardial cavity during the first postoperative hours in patients who underwent cardiac surgery. In this way, the blood and clot mixture can be diluted into a lower viscosity solution, thereby enhancing the evacuation of blood and clots from the pericardial space and preventing chest tube obstruction.

The Haermonics investigational device

Because CPPF therapy includes the dilution of the normal postoperative mediastinal chest tube drainage (MCTD), the clinical assessment of the exact amount of blood loss is more difficult. Yet, blood loss is an important factor in clinical decision making, namely the decision if the patient needs a surgical re-exploration for postoperative bleeding or not. Roughly, in patients who receive CPPF therapy, blood loss can be estimated by extracting the total inflow flushing volume from the total MCTD. This method was used in the experimental setting of the previous CPPF trails but is considered unsuitable for use in daily practice because of three reasons. First, the required registration of in- and outflow volume is labour intensive. Secondly, because this registration can only be done intermittently, which can be dangerous in case of a fast bleeding rate. Thirdly, blood loss calculation could potentially be inaccurate because sometimes, clinically insignificant, amounts of flushing fluid are retained or absorbed in the pericardial or pleural spaces, thereby making the blood loss calculation inaccurate.

The first commercial Haermonics device will have four essential functionalities that make CPPF therapy safe and feasible for daily clinical use. 1) Automatic monitoring of the outflow volume, 2) Quantification of the content of the outflow volume by means of real time and continuous haematocrit (hct) analysis of the MCTD, 3) Warming of the flushing fluid to body temperature and temperature measurements of the flushing fluid, and 4) Continuous intrapericardial pressure measurement. The investigational device that will be used in this study will have all these functionalities, but available data will not be used for clinical decision making yet.

Previous studies

CPPF, executed with a researcher instead of a medical device, has been investigated in two randomized clinical trials. The CPPF protocol included the inflow of 500 ml NaCl 0,9% flushing fluid into the pericardial cavity during the first 12 postoperative hours in patients who underwent cardiac surgery. In this way, the blood and clot mixture were diluted into a lower viscosity solution, thereby enhancing the evacuation of blood and clots from the pericardial space and preventing chest tube obstruction. In two distinct cardiac surgery populations, both trials showed CPPF led to a statistically significant reduction in the primary outcome, i.e., blood loss, while pooled data showed a statistically significant difference for the clinically most relevant secondary end points, like the incidence of re-interventions for either non-surgical bleeding and/or acute cardiac tamponade (0 vs. 8 in CPPF vs. control group).

The present study is powered to assess the effects of CPPF, executed by the Haermonics investigational device, in comparison with standard care on these clinically more relevant endpoints in a population of adult cardiac surgery patients.

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Nieuwegein, Netherlands
    • St. Antonius Ziekenhuis

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

In order to be eligible to participate in this study, a subject should be scheduled for a general cardiothoracic surgery procedure with the use of cardiopulmonary bypass, amongst others, the main categories are;

• Coronary artery bypass grafting (CABG),
• Valve surgery,
• CABG combined with valve surgery
• Elective patients scheduled for aortic surgery (including valve sparing root replacement (VSRR), Bentall procedures, ascending aorta- aortic arch replacement)

Including the initial study population:

• Patients scheduled for CABG with continued DAPT
• Patients with aIE scheduled for valve replacement
• Patients scheduled for complex or multiple cardiac (redo) procedures with an (expected) CPB time >300 minutes
• Patients undergoing aortic surgery with DHCA

Exclusion Criteria:

• Euroscore II > 20%
• Intraoperatively diaphragm injury leading to an open connection between the thoracic and abdominal cavity
• Age < 18
• Inability to understand study information
• Participation in any study involving an investigational drug or device
• Emergent procedures
• Procedures performed off pump, without the use of cardiopulmonary bypass.
• Minimal invasive cardiac surgery procedures (e.g. minithoracotomy and hemisternotomy)

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard care
Experimental: Continuous Postoperative Pericardial Flushing; Continuous Postoperative Pericardial Flushing (inflow of 500 ml NaCl 0,9% flushing fluid into the pericardial cavity during the first 8 postoperative hours) executed with the Haermonics investigational device	Device: CPPF; Continuous Postoperative Pericardial Flush

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of re-exploration	The incidence of re-exploration for either cardiac tamponade and/or excessive bleeding due to non-surgical bleeding.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess safety and feasibility of the Haermonics investigational device	Incidence of treatment related serious Adverse Events	8 hours
Hct-sensor validation	comparibility of the hct values of the chest drain volume measured by the Haermonics investigational device (hourly during the first 10 hours in the ICU and at chest tube removal) and hct values of chest drain samples (drawn from the outflow tube during the first 10 hours in the ICU and at chest tube removal) performed by the local laboratory.	8 hours
Number of participants with new onset postoperative fibrillation requiring medical therapy or electrocardioversion (ECV)	incidence of new onset postoperative fibrillation requiring medical therapy or electrocardioversion (ECV)	during hospital stay, average of 3-7 days
To investigate the clinical effects of CPPF on the use of blood products and administration of coagulation factors	Number of participants that reveived blood products and/or coagulation factors	during hospital stay, average of 3-7 days
To investigate the clinical effects of CPPF on the use of blood products and administration of coagulation factors	Number of units per patients	during hospital stay, average of 3-7 days
To investigate the clinical effects of CPPF on ICU and hospital stay	hospital stay in the operating hospital (days)	during hospital stay, average of 3-7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess cost-effectiveness	costs per QALY gained using the EQ-5D	3 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: European Regional Development Fund; Haermonics
• Investigators: Principal Investigator: R. Klautz, Prof, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): April 18, 2023

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 11, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: CABG; Continuous Postoperative Pericardial Flush (CPPF); Retained Blood Syndrome; Chest tubes [Mesh]; Blood Transfusion [mesh]; Therapeutic irrigation [Mesh]
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Postoperative Complications; Hemorrhage; Postoperative Hemorrhage; Cardiac Tamponade
• Other Study ID Numbers: NL74428

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