Dextran-based Priming vs. Crystalloid and Mannitol-based Priming Solution in Adult Cardiac Surgery

A Randomized Controlled Trial Comparing Dextran-based Priming (PrimECC), and Standard Crystalloid and Mannitol-based Priming Solution in Adult Cardiac Surgery

This study will compare two priming solutions for extracorporeal circulation, one based on Dextran 40, one based on crystalloid and mannitol. Primary endpoint is oncotic pressure during cardiopulmonary bypass. Secondary endpoints included fluid balance and organ functions.

Study Overview

• Status: Completed
• Conditions: Heart Disease
• Intervention / Treatment: Device: A colloid Dextran 40 solution for extracorporeal circulation; Device: Ringer-Acetate and Mannitol

Detailed Description

This is a prospective, single center, double-blinded, randomized controlled clinical trial. Eighty patients are randomized 1:1 to either cardiopulmonary bypass with the dextran-based solution or standard priming with Ringer-Acetate and Mannitol.

Primary endpoint will be oncotic pressure during cardio pulmonary bypass. Secondary endpoints include perioperative fluid balance, coagulation, platelet function, postoperative bleeding volume, transfusion requirements, renal function, liver function, pulmonary function, inflammatory activation and markers for brain and heart injury.

Blood samples for oncotic pressure measurements will be collected from an arterial line before and during surgery. Organ function will be assessed before surgery and 2 hours cardio pulmonary bypass.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • VGR
    • Gothenburg, VGR, Sweden, 41345
      • Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 50 - 75 years
• Elective cardiac surgery procedure with expected CBP time above 90 minutes
• Subject provides a legally effective informed consent.

Exclusion Criteria:

• Known previous cardiac surgery
• Coagulation disorder
• Malignancy
• Kidney failure
• Liver failure
• Ongoing septicaemia
• Ongoing antithrombotic treatment other than acetylsalicylic acid
• Systemic inflammatory disorders treated with corticosteroids
• Not able to understand Swedish

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: PrimECC; 1250 ml of a priming solution based on the colloid Dextran 40 to use for extracorporeal circulation.	Device: A colloid Dextran 40 solution for extracorporeal circulation; The oncotic pressure of the PrimECC solution is higher than that of a crystalloid Ringer-acetate/mannitol solution. It should maintain the plasma oncotic pressure during and after cardiopulmonary bypass (CPB). Subsequently, the leakage of fluids from the systemic circulation to the interstitial compartment during CPB can be reduced, and a higher plasma volume and a better fluid balance can be achieved.; Other Names: PrimECC
ACTIVE_COMPARATOR: Ringer-Acetate/Mannitol; 1250 ml of a priming solution based on the crystalloid Ringer-Acetate (1000ml) and Mannitol (250ml).	Device: Ringer-Acetate and Mannitol; Currently clinic standard for priming the CPB circuit.; Other Names: Standard crystalloid prime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oncotic pressure in plasma	The oncotic pressure in plasma is measured using an Osmomat 050 and reported in kPa. Points of measurement is before ECC and at 60 minutes into ECC	After 1 hour of cardiopulmonary bypass

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fluid balance	Patient fluid balance is registered from ECC-start until 24 hours post-ECC. Infusion of crystalloids and colloids and urine output is registered in ml.	Within 24 hours after cardiopulmonary bypass
Amount of bleeding	Bleeding is registered from ECC-start until 24 hours post-ECC. Intraoperative bleeding and postoperative chest tube drainage for 24 hours are added and registered in ml.	Within 24 hours after cardiopulmonary bypass
Amount of transfusions	Transfusions of red blood cells, platelets and plasma from ECC-start until 24 hours post-ECC are registered and reported in ml.	Within 24 hours after cardiopulmonary bypass
Change in coagulation (1).	Blood samples will be analyzed with modified rotational thromboelastometry (ROTEM) and calibrated automated thrombography. Points of measurement will be before ECC and at 2 hours post-ECC. Results will be reported as normal, above normal or below normal.	Within 2 hours after cardiopulmonary bypass
Change in coagulation (2).	Blood samples will be analyzed calibrated automated thrombography. Points of measurement will be before ECC and at 2 hours post-ECC. Results will be reported as normal, above normal or below normal.	Within 2 hours after cardiopulmonary bypass
Change in platelet function	Platelet function will be measured with impedance aggregometry (Multiplate). Points of measurement will be before ECC and at 2 hours post-ECC. Results will be reported as normal or below normal.	Within 2 hours after cardiopulmonary bypass
Change in renal function (1)	Renal function is measured as µmol/L of Creatinine in serum. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in renal function (2)	Renal tubular damage is measured by analysis of U-NAG. Urine is collected before ECC and at 60 minutes into ECC. Results will be reported as U-NAG/U-Creatinine ratio (U/min).	After 1 hour of cardiopulmonary bypass
Change in liver function (1)	The liver function is measured as µkat/L of ASAT in serum. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in liver function (2)	The liver function is measured as µkat/L of ALAT in serum. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in pulmonary function	The pulmonary function is measured by arterial blood gases assessing PaO2/FiO2 and reported in mmHg. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in ischemic heart injury marker.	The ischemic status of the heart is measures as ng/L of highly sensitive Troponin-T. Points of measurement will be before ECC and at 24 hours post-ECC.	Within 24 hours after cardiopulmonary bypass
Change in brain injury marker (1)	Brain damage is measured as ng/L Tau in plasma. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in brain injury marker (2)	Brain damage is measured as ng/L of NFL in serum. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in brain injury marker (3)	Brain damage is measured as µg/L of S100B in serum. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in brain injury marker (4)	Brain damage is measured as µg/L of NSE in serum. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass
Change in inflammatory activation	Inflammatory activation is measured as ng/L of IL-6 in plasma. Points of measurement will be before ECC and at 2 hours post-ECC.	Within 2 hours after cardiopulmonary bypass

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2016
• Primary Completion (ACTUAL): July 12, 2017
• Study Completion (ACTUAL): July 13, 2017

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (ESTIMATE): May 10, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 9, 2017
• Last Update Submitted That Met QC Criteria: October 6, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: extracorporeal circulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Anticoagulants; Plasma Substitutes; Blood Substitutes; Mannitol; Dextrans
• Other Study ID Numbers: 1003-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO