Back to resultsOptimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass, Part I (PRIME part I)
Primary Purpose
Endothelial Dysfunction, Hemolysis, Fluid Overload
Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
A: gelofusine + ringers
B: albumine + ringers
C: ringers + retrograde autologous priming
Sponsored by
About this trial
This is an interventional treatment trial for Endothelial Dysfunction focused on measuring Microcirculation, Cardiopulmonary bypass, Colloid oncotic pressure, Hemodilution, Hemolysis
Eligibility Criteria
Inclusion Criteria: Adult subjects Informed consent Elective coronary artery bypass surgery with cardiopulmonary bypass Exclusion Criteria: Emergency operations Re-operation Elective thoracic aortic surgery Elective valve surgery Combined procedure CABG and valve surgery Known allergy for human albumin or gelofusine
Sites / Locations
- Amsterdam UMC, AMC locationRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
A: gelofusine + ringers
B: albumin + ringers
C: ringers + retrograde autologous priming
Arm Description
Prime fluid strategy containing gelofusine and ringers
Prime fluid strategy containing albumin and ringers
Prime fluid strategy containing ringers combined with retrograde autologous priming
Outcomes
Primary Outcome Measures
Perfused vessel density (PVD, mm mm-²)
reflecting microcirculatory diffusion capacity
Perfused vessel density (PVD, mm mm-²)
reflecting microcirculatory diffusion capacity
Perfused vessel density (PVD, mm mm-²)
reflecting microcirculatory diffusion capacity
Perfused vessel density (PVD, mm mm-²)
reflecting microcirculatory diffusion capacity
Perfused vessel density (PVD, mm mm-²)
reflecting microcirculatory diffusion capacity
Secondary Outcome Measures
Colloid oncotic pressure (COP, mmHg)
colloid oncotic pressure in plasma
albumin (g L-¹)
concentration of albumin in plasma
hemolysis index (H-index)
the grade of hemolysis in plasma
haptoglobin (g L-¹)
concentration of haptoglobin in plasma
NO consumption (μmol L-¹)
consumption of nitric oxide in plasma
syndecan-1 (ng/ml)
Concentration of syndecan-1 in plasma
heparan sulphate (ng/ml)
concentration of heparan sulphate in plasma
hemoglobin (Hb, mmol L-¹)
concentration of hemoglobin in serum
hematocrit (Ht, L L-¹)
hematocrit in serum
perioperative use of packed red blood cells (PRBCs, mL)
amount of packed red blood cells
fluid balance (mL)
fluid balance
fluid requirements (mL)
Amount of fluids required
Total vessel density (TVD, mm mm-²)
density of capillaries reflecting the functional state of the microcirculatory diffusion capacity
Proportion of perfused vessels (PPV, %)
reflecting the aspect of heterogeneity of microcirculatory perfusion
Heterogeneity index
reflecting the aspect of heterogeneity of microcirculatory perfusion
Full Information
NCT ID
NCT05647057
First Posted
November 9, 2022
Last Updated
October 18, 2023
Sponsor
Amsterdam UMC, location VUmc
1. Study Identification
Unique Protocol Identification Number
NCT05647057
Brief Title
Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass, Part I
Acronym
PRIME part I
Official Title
Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2023 (Actual)
Primary Completion Date
August 15, 2024 (Anticipated)
Study Completion Date
January 15, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Acute microcirculatory perfusion disturbances is common in critical illness and associated with higher morbidity and mortality. Recent findings by the investigators' group showed that microcirculatory perfusion is disturbed during cardiac surgery with cardiopulmonary bypass (CPB) and remain disturbed up to 72 (seventy two) hours after surgery. A cardiopulmonary bypass is a machine which takes over heart and lung function, during the procedure. The disturbed microcirculation is associated with organ dysfunction induced by cardiac surgery using CPB, which is frequently seen (up to 42%, forty two percent) and results in a six-fold increase in mortality rate. The underlying cause of disturbed microcirculation is a higher endothelial permeability and vascular leakage and are a consequence of systemic inflammation, hemodilution (dilution of blood), hypothermia and hemolysis (breakdown of red blood cells). To gain the knowledge regarding disturbed microcirculation the investigators previously showed that hemodilution attributes to this disturbed perfusion. Hemodilution lowers colloid oncotic pressure (COP). Also, COP is affected by free hemoglobin, which increases with hemolysis and attributes to a disturbed microcirculation following CPB. This is interesting, as to the best of our knowledge, the effect of minimizing hemodilution and hemolysis during cardiac surgery on the microcirculatory perfusion has never been investigated, but could be the key factor in reducing organ dysfunction.
Detailed Description
In this project the investigators focus on reducing microcirculatory perfusion disturbances by exploring therapeutic approaches with different prime fluid strategies, by acting on COP (part I) and free hemoglobin scavenging with human albumin (part II).
In part I, patients undergoing elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass will be randomized in three groups receiving different prime fluid strategies. The study endpoint is the reduction in functional capillary density during the perioperative period. Sublingual microcirculatory measurements and blood sampling will take place after induction of anesthesia, during and after surgery to determine microcirculatory perfusion and parameters for hemodilution, hemolysis, COP, markers for endothelial damage and glycocalyx shedding. Measurements start on the day of surgery and end one day after surgery.
In part II, participants will be randomized in two groups receiving the first dose directly after aortic cross clamping and blood cardioplegia administration, and the second dose after the third blood cardioplegia administration (± 30 min after the first dose).The most optimal prime fluid in order to preserve microcirculatory perfusion from study one, will be used as prime fluid in the second study. Microcirculatory perfusion parameters will be measured at time points comparable with study one. Blood samples are taken to determine markers for hemodilution, hemolysis, COP and endothelial damage and glycocalyx shedding. For part II see trial registration: PRIME, part II.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endothelial Dysfunction, Hemolysis, Fluid Overload
Keywords
Microcirculation, Cardiopulmonary bypass, Colloid oncotic pressure, Hemodilution, Hemolysis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
In two consecutive randomized controlled trials, the investigators study the effect of prime fluid strategies on perfused vessel density (part I) and the effect of additional albumin during cardiopulmonary bypass compared with ringers on perfused vessel density (part II).
In this study part (I), the effect of prime fluid strategies on perfused vessel density.
Masking
ParticipantInvestigator
Masking Description
Double blind
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A: gelofusine + ringers
Arm Type
Active Comparator
Arm Description
Prime fluid strategy containing gelofusine and ringers
Arm Title
B: albumin + ringers
Arm Type
Active Comparator
Arm Description
Prime fluid strategy containing albumin and ringers
Arm Title
C: ringers + retrograde autologous priming
Arm Type
Active Comparator
Arm Description
Prime fluid strategy containing ringers combined with retrograde autologous priming
Intervention Type
Combination Product
Intervention Name(s)
A: gelofusine + ringers
Intervention Description
750 milliliter (mL) modified fluid gelatin (Braun Melsungen, Germany), 650 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands)
Intervention Type
Combination Product
Intervention Name(s)
B: albumine + ringers
Intervention Description
200 mL human albumin (20%, Sanquin, Amsterdam, Netherlands), 1200 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands)
Intervention Type
Combination Product
Intervention Name(s)
C: ringers + retrograde autologous priming
Intervention Description
1400 mL Ringer's solution (Baxter, Utrecht, Netherlands) and 100 mL mannitol (15%, Baxter, Utrecht, Netherlands) with retrograde autologous priming.
Retrograde autologous priming (RAP) is applied using clinical parameters such as Central Venous Pressure, Mean Arterial Pressure (MAP), and intra cardiac filling pressure based on Trans Esophageal Echo as guidance to the amount of fluid displaced. RAP is applied to a maximum volume of 475 mL provided that systolic blood pressure will remain >90 millimeter of mercury (mmHg). Phenylephrine can be administered up to 200 mcg to keep the system hemodynamics stable during RAP. In case of a body surface area <1.7m2, a maximum volume of 375 mL is desired. Once the desired amount of prime is displaced, the transfusion bag is clamped and CPB is started. If additional fluids are needed during CPB to maintain optimal perfusion, the displaced prime is used prior to the vasoplegia protocol.
Primary Outcome Measure Information:
Title
Perfused vessel density (PVD, mm mm-²)
Description
reflecting microcirculatory diffusion capacity
Time Frame
T1: within 5-10 minutes after induction of anesthesia
Title
Perfused vessel density (PVD, mm mm-²)
Description
reflecting microcirculatory diffusion capacity
Time Frame
T2 within 5-10 minutes after aortic cross clamping
Title
Perfused vessel density (PVD, mm mm-²)
Description
reflecting microcirculatory diffusion capacity
Time Frame
T3 within 5-10 minutes after weaning from cardiopulmonary bypass
Title
Perfused vessel density (PVD, mm mm-²)
Description
reflecting microcirculatory diffusion capacity
Time Frame
T4 within 15-30 min after arrival on the intensive care unit
Title
Perfused vessel density (PVD, mm mm-²)
Description
reflecting microcirculatory diffusion capacity
Time Frame
T5 twenty four (24) hours after arrival on the intensive care unit
Secondary Outcome Measure Information:
Title
Colloid oncotic pressure (COP, mmHg)
Description
colloid oncotic pressure in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
albumin (g L-¹)
Description
concentration of albumin in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
hemolysis index (H-index)
Description
the grade of hemolysis in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
haptoglobin (g L-¹)
Description
concentration of haptoglobin in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
NO consumption (μmol L-¹)
Description
consumption of nitric oxide in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
syndecan-1 (ng/ml)
Description
Concentration of syndecan-1 in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
heparan sulphate (ng/ml)
Description
concentration of heparan sulphate in plasma
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
hemoglobin (Hb, mmol L-¹)
Description
concentration of hemoglobin in serum
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
hematocrit (Ht, L L-¹)
Description
hematocrit in serum
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
perioperative use of packed red blood cells (PRBCs, mL)
Description
amount of packed red blood cells
Time Frame
Intraoperative during cardiac surgery, postoperative period up to 24 hours postoperative
Title
fluid balance (mL)
Description
fluid balance
Time Frame
Intraoperative during cardiac surgery, postoperative period up to 24 hours postoperative
Title
fluid requirements (mL)
Description
Amount of fluids required
Time Frame
Intraoperative during cardiac surgery, postoperative period up to 24 hours postoperative
Title
Total vessel density (TVD, mm mm-²)
Description
density of capillaries reflecting the functional state of the microcirculatory diffusion capacity
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Proportion of perfused vessels (PPV, %)
Description
reflecting the aspect of heterogeneity of microcirculatory perfusion
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Heterogeneity index
Description
reflecting the aspect of heterogeneity of microcirculatory perfusion
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Other Pre-specified Outcome Measures:
Title
Age
Description
Age in years
Time Frame
Preoperative
Title
Gender
Description
Gender (male/female)
Time Frame
Preoperative
Title
Body Surface Area (BSA)
Description
BSA in m2
Time Frame
Preoperative
Title
Smoking
Description
Medical history of smoking (yes/no)
Time Frame
Preoperative
Title
Diabetes on medication
Description
Medical history of diabetes on medication (yes/no)
Time Frame
Preoperative
Title
Comorbidities
Description
Other comorbidities in medical history (yes/no)
Time Frame
Preoperative
Title
EuroSCORE II
Description
The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II predicts risk of in-hospital mortality after cardiac surgery.
Time Frame
Preoperative
Title
CPB time (min)
Description
Cardiopulmonary bypass time in minutes
Time Frame
intraoperative
Title
Aortic cross clamping time (AoX time, min)
Description
Aortic cross clamping time in minutes
Time Frame
intraoperative
Title
heparin (IU)
Description
Dosing of heparin in international units
Time Frame
intraoperative
Title
protamin (mg)
Description
dosing of protamin
Time Frame
intraoperative
Title
Activated Clotting Time (ACT, min)
Description
ACT in minutes
Time Frame
intraoperative
Title
Temperature (celsius)
Description
Temperature in celsius
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Oxygen saturation (Sat, %)
Description
Oxygen saturation in %
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Urine production (ml)
Description
Urine production
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Blood pressure (mmHg)
Description
Blood pressure (mmHg)
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Noradrenaline infusion
Description
Noradrenaline infusion (mcg/kg/min)
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Phenylephrine
Description
Phenylephrine (mcg)
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Vasopressin (IU/min)
Description
Vasopressin (IU/min)
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Methylene Blue (mg)
Description
Methylene blue (mg)
Time Frame
T1, 5-10 min after induction of anesthesia; T2, 5-10 min after aortic cross clamping; T3, 5-10 min after weaning from cardiopulmonary bypass; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Lactate (mmol/L)
Description
Serum lactate
Time Frame
T1, 5-10 min after induction of anesthesia; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Creatinin levels (umol/L)
Description
serum creatinin level
Time Frame
T1, 5-10 min after induction of anesthesia; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
estimated glomerular filtration rate (eGFR, ml/min/1,73 m2)
Description
estimated glomerular filtration rate
Time Frame
T1, 5-10 min after induction of anesthesia; T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit.
Title
Blood product use
Description
Blood product use (ml)
Time Frame
Intraoperative and up to 24 hours postoperative
Title
Blood loss (ml)
Description
Blood loss
Time Frame
T4, 15-30 min after arrival on the intensive care unit; T5, 24 hours after arrival on the intensive care unit
Title
Duration of mechanical ventilation (hours)
Description
Duration of mechanical ventilation (hours)
Time Frame
Postoperative until 30 days postoperative
Title
ICU stay (hours)
Description
ICU stay (hours)
Time Frame
Postoperative until 30 days postoperative
Title
Hospital stay (days)
Description
Days until hospital discharge (days)
Time Frame
Postoperative until 30 days postoperative
Title
Acute Kidney injury (AKI)
Description
Acute kidney injury (yes/no)
Time Frame
Postoperative until 30 days postoperative
Title
Respiratory failure
Description
Respiratory failure (yes/no)
Time Frame
Postoperative until 30 days postoperative
Title
Pneumonia
Description
Pneumonia (yes/no)
Time Frame
Postoperative until 30 days postoperative
Title
non-preexisting atrial fibrillation
Description
non-preexisting atrial fibrillation (yes/no)
Time Frame
Postoperative until 30 days postoperative
Title
re-do surgery
Description
re-do surgery (yes/no)
Time Frame
Postoperative until 30 days postoperative
Title
Extra corporeal membrane oxygenation (ECMO)
Description
Extra corporeal membrane oxygenation (yes/no)
Time Frame
Postoperative until 30 days postoperative
Title
Mortality
Description
In-hospital mortality (yes/no)
Time Frame
Postoperative until 30 days postoperative
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult subjects
Informed consent
Elective coronary artery bypass surgery with cardiopulmonary bypass
Exclusion Criteria:
Emergency operations
Re-operation
Elective thoracic aortic surgery
Elective valve surgery
Combined procedure CABG and valve surgery
Known allergy for human albumin or gelofusine
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
A.M. Beukers, MD
Phone
020-4444444
Email
a.beukers@amsterdamumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A.B.A. Vonk, MD, PhD
Organizational Affiliation
Cardiothoracic surgeon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam UMC, AMC location
City
Amsterdam
State/Province
Noord Holland
ZIP/Postal Code
1105AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A.M. Beukers, MD
Phone
020-4444444
Email
a.beukers@amsterdamumc.nl
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Upon request
IPD Sharing Time Frame
Upon request
Learn more about this trial
Optimization of Prime Fluid Strategy to Preserve Microcirculatory Perfusion During Cardiac Surgery With Cardiopulmonary Bypass, Part I
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