Comparison of Priming Constituents in Patients Undergoing CPB Assisted Cardiac Surgery: HES 130/0.4 or Albumin 5%

April 30, 2019 updated by: Jo-Anne Marcoux, University of Saskatchewan
The purpose of the study is to determine which priming fluid is the safest for use for priming the heart-lung machine used during cardiopulmonary bypass for patients undergoing cardiac surgery. The fluids to be compared are albumin and voluven. A control group will receive only crystalloid.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Project title:

Comparison of priming constituents in patients undergoing CPB assisted cardiac surgery: 6% HES 130/0.4 or Albumen 5%

Principal investigator:

Jo-Anne Marcoux M. Sc., CPC, CCP

Department:

Clinical Perfusion

Sub-investigators:

Victor Uppal B. Sc., CPC, CCP Taras Mycyk MD, FRCSC,

Research will be conducted at: the cardiac operating rooms of the Royal University Hospital, and affiliated hospitals

Hypothesis It is hypothesized that the use of an artificial colloid (6% hydroxyethyl starch 130/0.4) (HES) as a priming constituent is more disruptive to the coagulation and renal systems compared to the use of human derived albumen.

It is further hypothesized that patients who undergo cardiopulmonary bypass (CPB) with HES 130/0.4 as a priming constituent will demonstrate decreased creatinine clearance and increased post-operative bleeding and transfusion requirements.

Academic validity Permissive hemodilution results when crystalloids and colloids are substituted for blood as priming fluids in the cardiopulmonary bypass circuit. While there are obvious benefits to decreasing autologous blood exposure to the patients undergoing CPB, determining the most physiological substitution has not been conclusively resolved. Historically, available HES had a greater molecular weight then the product currently in use and was associated with detrimental adverse events when compared to saline as fluid replacement therapy (5.3% vs. 2.8%, p < 0.001). (1) When albumin was compared to HES 450/0.7 and HES 200/0.05 for fluid management in adult CPB surgery, (18 trials of 970 patients) HES increased transfusion of red blood cells by 28.4% (p = 0.027), increased the transfusion of fresh-frozen plasma by 30.6% (p = 0.008) and increased the transfusion of platelets by 29.8% (p = 0.027). HES 130/0.4 could not be compared to albumen in this same study because there was insufficient data collected. However, no significant differences were found when comparing transfusion requirements between HES 450/0.7, HES 200/0.05 and HES 130/0.4. (2) Viscoelastic device analysis concluded that the administration of HES 130/0.4 in patients or healthy volunteers resulted in a weaker and smaller clot. (3) Short-time infusions of HES 200/0.5 and HES 130/0.4 after cardiac surgery produced a temporary impairment of fibrin formation and clot strength while human albumin had no effect. (4)

In regards to the association between HES and renal failure, on the one hand use of HES 130/0.4 as a priming fluid used in children undergoing CPB did not result in any negative effects on renal function and was safe to use in the pediatric population. (5) On the other hand, when used for resuscitative measures in 7000 randomly assigned patients admitted to intensive care, though there was no difference in 90 day mortality between the group assigned HES 130/0.4 and the group assigned saline, more patients assigned HES 130/0.4 required renal replacement therapy. (1) When used immediately after CPB in a double-blind clinical trial comparing 4% gelatin, Ringer's solution and HES 130/0.4, it was found that significantly lower mean creatinine levels were found in the HES 130/0.4 group compared to the other two groups. (6)

Our research is directed toward determining conclusively if HES 130/0.4 has a similar risk profile to HES 450/0.7 and HES 200/0.05 when used as a priming constituent for the CPB circuit. Additionally we will determine if an albumin/crystalloid prime is superior to a HES 130/0.4/crystalloid prime. A fully crystalloid prime control group will be included for a controlled comparison.

Research design/Methods

The will be a randomized, control trial. Three groups of subjects will be studied:

  1. Control group: Crystalloid prime

    • 2 L crystalloid prime,
    • 2.5 mL/kg Mannitol 20%,
    • 1 ampoule of NaHCO-3 (50 mL),
    • 10,000 iu heparin

  2. Voluven (light?):

    • HES 130/0.4 prime 500 mL
    • balance of crystalloid
    • 2.5 mL/kg Mannitol 20%,
    • 1 ampoule of NaHCO-3 (50 mL),
    • 10,000 iu heparin

  3. Albumin:

    • Human albumin 500 mL 5%
    • balance of crystalloid
    • 2.5 mL/kg Mannitol 20%,
    • 1 ampoule of NaHCO-3 (50 mL),
    • 10,000 iu heparin

Statistical Analysis We would like to have 7000 subjects included in this research project. Study populations and outcomes for patients undergoing CPB assisted cardiac surgery are extremely varied. An extremely large population size will be necessary to answer the research question proposed as the priming differences in question result in very subtle outcome differences.

All patients will undergo CPB assisted cardiac surgery. Blood samples will be drawn at routine intervals from each subject. Blood will be sampled upon entering the operating room, at the completion of surgery, and at 24 hours post-operatively.

The amount of blood drawn will not be above and beyond the usual tests and analyses related to the care of all affected patients undergoing CPB assisted cardiac surgery.

a)

Inclusion criteria:

  • greater than 50 years of age
  • will be afflicted with co-morbidities associated with cardiac disease (increased cholesterol, hypertension, smoking, diabetes, previous myocardial infarctions and decreased ejection fraction)

Exclusion criteria:

  • emergencies
  • renal failure
  • dialysis dependent

The cardiac center involved to date is:

RUH Saskatoon The goal is recruitment of all cardiac centers in western Canada.

Primary end-points: are postoperative bleeding and transfusion of autologous units of red blood cells, frozen plasma and platelets.

Secondary end-points: Post-operative renal function parameter creatinine

Data collection will be ongoing. Interim analysis will be completed once half the patients have been recruited with final statistical analysis to be conducted once data capture is complete.

Potential Significance/Justification CPB assisted cardiac surgical outcomes have improved tremendously since the first such procedure was done in 1953. Outcome improvements have always come from small changes that were evidence based. This research project means to determine the safest prime for a procedure, which occurs roughly 2,000,000/year throughout the world. In regards to the cost of the study solutions in question, there is a $4.10 difference between the cost of 500 mL of HES 130/0.4 prime and 500 mL of 5% Albumin with HES 130/0.4 being more expensive.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Royal University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

patients undergoing cardiopulmonary bypass assisted cardiac surgery

-

Exclusion Criteria:

emergencies and patients in renal failure or dialysis -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Human Albumin
Human albumin solution used as part of the priming volume for the cardiopulmonary bypass circuit.
Other: Human Albumin
Used as a constituent for priming the CPB circuit
Other Names:
  • Albumin 5%
  • Albumin 25%
ACTIVE_COMPARATOR: Voluven or hydroethylstarch HES 130/0.4
Hydroethylstarch HES 130/0.4 used as part of the priming volume for the cardiopulmonary bypass circuit.
Other: Voluven
Used as a constituent for priming the CPB circuit
Other Names:
  • Hydroethylstarch HES130/0.4
PLACEBO_COMPARATOR: Crystalloid
Crystalloid will be used to prime the cardiopulmonary bypass circuit
Other: prime crystalloid
used for priming the CPB circuit
Other Names:
  • saline 0.9%
  • Plasmalyte
  • Ringer's lactate
  • Normosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-operative bleeding and transfusion requirements
Time Frame: 24-48 hours post-operatively
Postoperative cardiac patients have chest tubes in place which drain any blood oozing from around the pericardial cavity. The chest tubes are attached to a blood collection apparatus which measures the amount of blood loss. Too much post-operative blood loss results in a transfusion requirement of red blood cells, plasma and/or platelets.
24-48 hours post-operatively

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
renal function, creatinine levels
Time Frame: 24-48 hours post-operatively
Use of some colloids have been associated with a deterioration of renal function. Data will be collected post-operatively to determine he effect of the different priming fluids on renal function
24-48 hours post-operatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Saskatchewan

Investigators

  • Principal Investigator: Jo-Anne E Marcocoux, M. Sc., Royal University Hospital Foundation
  • Principal Investigator: Jo-Anne E Marcoux, M. Sc., RUH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (ANTICIPATED)

November 1, 2016

Study Completion (ANTICIPATED)

November 1, 2017

Study Registration Dates

First Submitted

May 6, 2013

First Submitted That Met QC Criteria

May 6, 2013

First Posted (ESTIMATE)

May 8, 2013

Study Record Updates

Last Update Posted (ACTUAL)

May 3, 2019

Last Update Submitted That Met QC Criteria

April 30, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ruh/westerncan/primestudy

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Coronary Artery Disease

Clinical Trials on Human Albumin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ghana

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe