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

Sponsor

University of Saskatchewan (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01849757

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Aortic Valve Disease Mitral Valve Disease	Other: prime crystalloid Other: Human Albumin Other: Voluven	N/A

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.

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2013

Anticipated Primary Completion Date :

Nov 1, 2016

Anticipated Study Completion Date :

Nov 1, 2017

Arms and Interventions

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% Normosol Ringer's lactate Plasmalyte

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%

Normosol

Ringer's lactate

Plasmalyte

Outcome Measures

Primary Outcome Measures

Post-operative bleeding and transfusion requirements [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.

Secondary Outcome Measures

renal function, creatinine levels [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