Comparison of Priming Constituents in Patients Undergoing CPB Assisted Cardiac Surgery: HES 130/0.4 or Albumin 5%
Primary Purpose
Coronary Artery Disease, Aortic Valve Disease, Mitral Valve Disease
Status
Withdrawn
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
prime crystalloid
Human Albumin
Voluven
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Artery Disease focused on measuring Cardiopulmonary bypass, prime, crystalloid, albumin, HES 130/0.4
Eligibility Criteria
Inclusion Criteria:
patients undergoing cardiopulmonary bypass assisted cardiac surgery
-
Exclusion Criteria:
emergencies and patients in renal failure or dialysis -
Sites / Locations
- Royal University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Human Albumin
Voluven or hydroethylstarch HES 130/0.4
Crystalloid
Arm Description
Human albumin solution used as part of the priming volume for the cardiopulmonary bypass circuit.
Hydroethylstarch HES 130/0.4 used as part of the priming volume for the cardiopulmonary bypass circuit.
Crystalloid will be used to prime the cardiopulmonary bypass circuit
Outcomes
Primary Outcome Measures
Post-operative bleeding and transfusion requirements
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01849757
Brief Title
Comparison of Priming Constituents in Patients Undergoing CPB Assisted Cardiac Surgery: HES 130/0.4 or Albumin 5%
Official Title
Comparison of Priming Constituents in Patients Undergoing CPB Assisted Cardiac Surgery: HES 130/0.4 or Albumin 5%
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Pentaspan is no longer used at our institution. Pentaspan was an arm of the study
Study Start Date
November 2013 (undefined)
Primary Completion Date
November 2016 (Anticipated)
Study Completion Date
November 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Saskatchewan
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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:
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
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Aortic Valve Disease, Mitral Valve Disease
Keywords
Cardiopulmonary bypass, prime, crystalloid, albumin, HES 130/0.4
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Human Albumin
Arm Type
Active Comparator
Arm Description
Human albumin solution used as part of the priming volume for the cardiopulmonary bypass circuit.
Arm Title
Voluven or hydroethylstarch HES 130/0.4
Arm Type
Active Comparator
Arm Description
Hydroethylstarch HES 130/0.4 used as part of the priming volume for the cardiopulmonary bypass circuit.
Arm Title
Crystalloid
Arm Type
Placebo Comparator
Arm Description
Crystalloid will be used to prime the cardiopulmonary bypass circuit
Intervention Type
Other
Intervention Name(s)
prime crystalloid
Other Intervention Name(s)
saline 0.9%, Normosol, Ringer's lactate, Plasmalyte
Intervention Description
used for priming the CPB circuit
Intervention Type
Other
Intervention Name(s)
Human Albumin
Other Intervention Name(s)
Albumin 5%, Albumin 25%
Intervention Description
Used as a constituent for priming the CPB circuit
Intervention Type
Other
Intervention Name(s)
Voluven
Other Intervention Name(s)
Hydroethylstarch HES130/0.4
Intervention Description
Used as a constituent for priming the CPB circuit
Primary Outcome Measure Information:
Title
Post-operative bleeding and transfusion requirements
Description
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.
Time Frame
24-48 hours post-operatively
Secondary Outcome Measure Information:
Title
renal function, creatinine levels
Description
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
Time Frame
24-48 hours post-operatively
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients undergoing cardiopulmonary bypass assisted cardiac surgery
-
Exclusion Criteria:
emergencies and patients in renal failure or dialysis -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jo-Anne E Marcocoux, M. Sc.
Organizational Affiliation
Royal University Hospital Foundation
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jo-Anne E Marcoux, M. Sc.
Organizational Affiliation
RUH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal University Hospital
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 0W8
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
23075127
Citation
Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, Glass P, Lipman J, Liu B, McArthur C, McGuinness S, Rajbhandari D, Taylor CB, Webb SA; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012 Nov 15;367(20):1901-11. doi: 10.1056/NEJMoa1209759. Epub 2012 Oct 17. Erratum In: N Engl J Med. 2016 Mar 31;374(13):1298.
Results Reference
background
PubMed Identifier
22578894
Citation
Navickis RJ, Haynes GR, Wilkes MM. Effect of hydroxyethyl starch on bleeding after cardiopulmonary bypass: a meta-analysis of randomized trials. J Thorac Cardiovasc Surg. 2012 Jul;144(1):223-30. doi: 10.1016/j.jtcvs.2012.04.009. Epub 2012 May 9.
Results Reference
background
PubMed Identifier
21989733
Citation
Hartog CS, Reuter D, Loesche W, Hofmann M, Reinhart K. Influence of hydroxyethyl starch (HES) 130/0.4 on hemostasis as measured by viscoelastic device analysis: a systematic review. Intensive Care Med. 2011 Nov;37(11):1725-37. doi: 10.1007/s00134-011-2385-z. Epub 2011 Oct 12.
Results Reference
background
PubMed Identifier
19095827
Citation
Schramko AA, Suojaranta-Ylinen RT, Kuitunen AH, Kukkonen SI, Niemi TT. Rapidly degradable hydroxyethyl starch solutions impair blood coagulation after cardiac surgery: a prospective randomized trial. Anesth Analg. 2009 Jan;108(1):30-6. doi: 10.1213/ane.0b013e31818c1282.
Results Reference
background
PubMed Identifier
23228215
Citation
Akkucuk FG, Kanbak M, Ayhan B, Celebioglu B, Aypar U. The effect of HES (130/0.4) usage as the priming solution on renal function in children undergoing cardiac surgery. Ren Fail. 2013;35(2):210-5. doi: 10.3109/0886022X.2012.747139. Epub 2012 Dec 11.
Results Reference
background
PubMed Identifier
23044498
Citation
Alavi SM, Ahmadi BB, Baharestani B, Babaei T. Comparison of the effects of gelatin, Ringer's solution and a modern hydroxyl ethyl starch solution after coronary artery bypass graft surgery. Cardiovasc J Afr. 2012 Sep;23(8):428-31. doi: 10.5830/CVJA-2012-026.
Results Reference
background
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Comparison of Priming Constituents in Patients Undergoing CPB Assisted Cardiac Surgery: HES 130/0.4 or Albumin 5%
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