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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2013 by University of Saskatchewan
Sponsor:
Information provided by (Responsible Party):
Jo-Anne Marcoux, University of Saskatchewan
ClinicalTrials.gov Identifier:
NCT01849757
First received: May 6, 2013
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention
Coronary Artery Disease
Aortic Valve Disease
Mitral Valve Disease
Other: prime crystalloid
Other: Human Albumin
Other: Voluven

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Comparison of Priming Constituents in Patients Undergoing CPB Assisted Cardiac Surgery: HES 130/0.4 or Albumin 5%

Resource links provided by NLM:


Further study details as provided by University of Saskatchewan:

Primary Outcome Measures:
  • Post-operative bleeding and transfusion requirements [ Time Frame: 24-48 hours post-operatively ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • renal function, creatinine levels [ Time Frame: 24-48 hours post-operatively ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 7000
Study Start Date: November 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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%
  • Normosol
  • Ringer's lactate
  • Plasmalyte

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

patients undergoing cardiopulmonary bypass assisted cardiac surgery

-

Exclusion Criteria:

emergencies and patients in renal failure or dialysis -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849757

Contacts
Contact: Jo-Anne E. Marcoux, M. Sc. 306-655-2128 laterreur2@yahoo.ca
Contact: Victor Uppal, B. Sc. 306-655-2128 victoruppal12@gmail.com

Locations
Canada, Saskatchewan
Royal University Hospital Not yet recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Contact: Marcoux    306-6552128      
Contact: Uppal    306-6552128      
Principal Investigator: Jo-Anne E Marcoux, M. Sc.         
Sponsors and Collaborators
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
  More Information

Publications:

Responsible Party: Jo-Anne Marcoux, Perfusionist M. Sc., CPC, CCP, University of Saskatchewan
ClinicalTrials.gov Identifier: NCT01849757     History of Changes
Other Study ID Numbers: ruh/westerncan/primestudy
Study First Received: May 6, 2013
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Saskatchewan:
Cardiopulmonary bypass
prime
crystalloid
albumin
HES 130/0.4

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Valve Diseases
Heart Defects, Congenital
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Albunex
Plasma-lyte 148
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions
Ophthalmic Solutions
Pharmaceutical Solutions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014