Cardiac Surgical ProceduresFLUIDNCT05308589
CPPF After General Cardiac Surgery
A study testing CPPF in people with Cardiac Surgical Procedures and Retained Blood Syndrome, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 4 sites in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgical Procedures, Retained Blood Syndrome, Cardiac Tamponade
- What is being tested?
- CPPF
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 4 sitesNetherlands
- Study dates
- 2 Nov 2021to 18 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 10Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites
Amsterdam UMC
Amsterdam
Catharina Ziekenhuis
Eindhoven
Leiden University Medical Center
Leiden
St. Antonius Ziekenhuis
Nieuwegein
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiac Surgical Procedures, Retained Blood Syndrome, Cardiac Tamponade, Postoperative Hemorrhage
- Being tested
- CPPF
- Keywords
- Continuous Postoperative Pericardial Flush (CPPF), CABG, Retained Blood Syndrome, Chest tubes [Mesh], Blood Transfusion [mesh], Therapeutic irrigation [Mesh]
- Medical subject headings
- Cardiac Tamponade, Postoperative Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPPFDevice
Continuous Postoperative Pericardial Flush
| Study group | Role | What they receive |
|---|---|---|
| Continuous Postoperative Pericardial Flushing | Experimental | 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 Receives: Device: CPPF |
| Control | No intervention | Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of re-exploration
The incidence of re-exploration for either cardiac tamponade and/or excessive bleeding due to non-surgical bleeding.
Measured: 7 days
Secondary outcomes (6)
To assess safety and feasibility of the Haermonics investigational device
Incidence of treatment related serious Adverse Events
Measured: 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.
Measured: 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)
Measured: 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
Measured: 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
Measured: 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)
Measured: during hospital stay, average of 3-7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2022
- Study start2 Nov 2021
- Primary completion18 Apr 2023
- Study completion18 Apr 2023
Why it stopped: The study no longer fits our strategic goals. The preliminary results of FLUID have led to an improved version of the current device. We believe it is necessary to initiate a new study, with the improved version of the device.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac Surgical ProceduresStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Collaborators
- Haermonics BV, European Regional Development Fund
- Responsible party
- Principal investigator, Eva Diephuis, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- R. Klautz, Prof, Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05308589
- Sponsor's protocol ID
- NL74428
- Acronym
- FLUID
- Status last verified
- May 2024
- First submitted
- 28 Feb 2022
- Last updated
- 14 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous Postoperative Pericardial Flushing After General Cardiac Surgery Procedures With the Haermonics Investigational Device: Study Protocol of the FLUID (FLUsh With Investigational Device) Trial
- ClinicalTrials.gov ID
- NCT05308589
- Acronym / sponsor ID
- FLUID / NL74428
- Conditions
- Cardiac Surgical Procedures, Retained Blood Syndrome, Cardiac Tamponade, Postoperative Hemorrhage
- Keywords
- Continuous Postoperative Pericardial Flush (CPPF), CABG, Retained Blood Syndrome, Chest tubes [Mesh], Blood Transfusion [mesh], Therapeutic irrigation [Mesh]
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study no longer fits our strategic goals. The preliminary results of FLUID have led to an improved version of the current device. We believe it is necessary to initiate a new study, with the improved version of the device.
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Haermonics BV, European Regional Development Fund
- Study start
- 2 Nov 2021 (actual)
- Primary completion
- 18 Apr 2023 (actual)
- Study completion
- 18 Apr 2023 (actual)
- First posted
- 4 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous Postoperative Pericardial Flushing | Experimental | Device: CPPFContinuous 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 |
| Control | No intervention | –Standard care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CPPFContinuous Postoperative Pericardial Flush | Device | Continuous Postoperative Pericardial Flushing |
Primary outcome
Incidence of re-exploration
Time frame: 7 days
The incidence of re-exploration for either cardiac tamponade and/or excessive bleeding due to non-surgical bleeding.
6 secondary outcomes
To assess safety and feasibility of the Haermonics investigational device
Time frame: 8 hours
Hct-sensor validation
Time frame: 8 hours
Number of participants with new onset postoperative fibrillation requiring medical therapy or electrocardioversion (ECV)
Time frame: 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
Time frame: 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
Time frame: during hospital stay, average of 3-7 days
To investigate the clinical effects of CPPF on ICU and hospital stay
Time frame: during hospital stay, average of 3-7 days
Results and safety
The study was stopped early (reason given: The study no longer fits our strategic goals. The preliminary results of FLUID have led to an improved version of the current device. We believe it is necessary to initiate a new study, with the improved version of the device.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R. Klautz, Prof principal investigator
Amsterdam UMC
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CPPF in people with Cardiac Surgical Procedures and Retained Blood Syndrome, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The study no longer fits our strategic goals. The preliminary results of FLUID have led to an improved version of the current device. We believe it is necessary to initiate a new study, with the improved version of the device.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of re-exploration (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.