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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05647200
Other study ID # NL82500.029.22, part II
Secondary ID
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date October 15, 2023
Est. completion date January 15, 2025

Study information

Verified date April 2023
Source Amsterdam UMC, location VUmc
Contact A.M. Beukers, MD
Phone 020-4444444
Email a.beukers@amsterdamumc.nl
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Acute microcirculatory perfusion disturbances is common in critical illness and associated with increased morbidity and mortality. Recent findings by our 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 forty two percent, 42%) 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.


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. For part I see trial registration: PRIME, part I. 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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 64
Est. completion date January 15, 2025
Est. primary completion date July 15, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Treatment: additional albumin during cardiopulmonary bypass
Treatment group (T): administration of 100 mL Human Albumin (20%), first dose directly after aortic cross clamping and blood cardioplegia administration, second dose after the third blood cardioplegia administration (± 30 min after the first dose).
control: additional ringers during cardiopulmonary bypass
Control group (C): administration of 100 mL of Ringer's solution, first dose directly after aortic cross clamping and blood cardioplegia administration, second dose after the third blood cardioplegia administration (± 30 min after the first dose).

Locations

Country Name City State
Netherlands Amsterdam UMC, AMC location Amsterdam Noord Holland

Sponsors (1)

Lead Sponsor Collaborator
Amsterdam UMC, location VUmc

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Other Age Age in years Preoperative
Other Gender Gender (male/female) Preoperative
Other Body Surface area (BSA) BSA in m2 Preoperative
Other Smoking Medical history of smoking (yes/no) Preoperative
Other Diabetes on medication Medical history of diabetes on medication (yes/no) Preoperative
Other Comorbidities Other comorbidities in medical history (yes/no) Preoperative
Other EuroSCORE II The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II predicts risk of in-hospital mortality after cardiac surgery. preoperative
Other CPB time (min) Cardiopulmonary bypass time in minutes Intraoperative
Other Aortic cross clamping time (AoX time, min) Aortic cross clamping time in minutes Intraoperative
Other heparin (IU) Dosing of heparin in international units Intraoperative
Other protamin (mg) Dosing of protamin Intraoperative
Other Activated clotting time (ACT, min) Activated clotting time in minutes Intraoperative
Other Temperature (celsius) Temperature in Celsius 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 Oxygen saturation (Sat, %) Oxygen saturation in % 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 Urine production (ml) Urine production 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 Blood pressure (mmHg) Blood pressure (mmHg) 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 Noradrenaline Noradrenaline (mcg/kg/min) 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 Phenylephrine Phenylephrine (mcg) 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 Vasopressin (IU/min) Vasopressin (IU/min) 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 Methylene Blue Methylene Blue (mg) 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 Lactate (mmol/L) Serum lactate 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.
Other Creatinin levels (umol/L) serum creatinin level 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.
Other estimated glomerular filtration rate (eGFR)(ml/min/1,73 m2) estimated glomerular filtration rate 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.
Other Blood product use Blood product use (ml) Intraoperative and postoperative up to 24 hours postoperative
Other Blood loss (ml) Blood loss Intraoperative and postoperative up to 24 hours postoperative
Other Duration of mechanical ventilation (hours) Duration of mechanical ventilation (hours) Postoperative until 30 days postoperative
Other ICU stay (hours) ICU stay (hours) Postoperative until 30 days postoperative
Other Hospital stay (days) Days until hospital discharge (days) Postoperative until 30 days postoperative
Other Acute kidney injury (AKI) Acute kidney injury (yes/no) Postoperative until 30 days postoperative
Other Respiratory failure Respiratory failure (yes/no) Postoperative until 30 days postoperative
Other Pneumonia pneumonia (yes/no) Postoperative until 30 days postoperative
Other non-preexisting atrial fibrillation non-preexisting atrial fibrillation (yes/no) Postoperative until 30 days postoperative
Other re-do surgery re-do surgery (yes/no) Postoperative until 30 days postoperative
Other Extra corporeal membrane oxygenation (ECMO) Extra corporeal membrane oxygenation (yes/no) Postoperative until 30 days postoperative
Other Mortality in-hospital mortality (yes/no) Postoperative until 30 days postoperative
Primary Perfused vessel density (PVD, mm mm-²) reflecting microcirculatory diffusion capacity Timepoint 1: 5-10 min after induction of anesthesia
Primary Perfused vessel density (PVD, mm mm-²) reflecting microcirculatory diffusion capacity Timepoint 2: 5-10 min after aortic cross clamping
Primary Perfused vessel density (PVD, mm mm-²) reflecting microcirculatory diffusion capacity Timepoint 3: 5-10 min after weaning from cardiopulmonary bypass
Primary Perfused vessel density (PVD, mm mm-²) reflecting microcirculatory diffusion capacity Timepoint 4: 15-30 min after arrival on the intensive care unit
Primary Perfused vessel density (PVD, mm mm-²) reflecting microcirculatory diffusion capacity Timepoint 5: twenty four (24) hours after arrival on the intensive care unit
Secondary Colloid oncotic pressure (COP, mmHg) colloid oncotic pressure in plasma 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.
Secondary albumin (g L-¹) concentration of albumin in plasma 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.
Secondary hemolysis index (H-index) the grade of hemolysis in plasma 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.
Secondary haptoglobin (g L-¹) concentration of haptoglobin in plasma 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.
Secondary NO consumption (µmol L-¹) consumption of nitric oxide in plasma 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.
Secondary syndecan-1 (ng/ml) Concentration of syndecan-1 in plasma 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.
Secondary heparan sulphate (ng/ml) concentration of heparan sulphate in plasma 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.
Secondary hemoglobin (Hb, mmol L-¹) concentration of hemoglobin in serum 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.
Secondary hematocrit (Ht, L L-¹) hematocrit in serum 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.
Secondary perioperative use of packed red blood cells (PRBCs, mL) amount of packed red blood cells intraoperative and postoperative up to 24 hours postoperative
Secondary fluid balance (mL) fluid balance intraoperative and postoperative up to 24 hours postoperative
Secondary fluid requirements (mL) Amount of fluids required intraoperative and postoperative up to 24 hours postoperative
Secondary Total vessel density (TVD, mm mm-²) density of capillaries reflecting the functional state of the microcirculatory diffusion capacity 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.
Secondary Proportion of perfused vessels (PPV, %) reflecting the aspect of heterogeneity of microcirculatory perfusion 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.
Secondary Heterogeneity index reflecting the aspect of heterogeneity of microcirculatory perfusion 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.
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