Clinical trial NCT00038454: Phase II Study To Evaluate The Safety and Efficacy of Hemoglobin Raffimer in Patients Undergoing First Time CABG Surgery
Official title: A Phase II, Randomized, Single-Blind, Controlled Clinical Trial to Evaluate the Efficacy and Safety of Hemolink[Tm] (o-Raffinose Cross-Linked Human Hemoglobin) in Subjects Undergoing Primary Coronary Artery Bypass Grafting Surgery
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Cardiovascular Disease
Keywords: Oxygen Therapeutics
CABG
Transfusion
Lead sponsor: Hemosol
Sponsor class: INDUSTRY
First posted: 2002-05-31
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of Hemolink™ in combination with Intraoperative Autologous Donation (IAD) versus control (IAD alone) in facilitating avoidance of allogeneic RBC transfusion during and following primary CABG surgery

Detailed description: All subjects who consent to take part in the protocol and who meet the inclusion/exclusion criteria will undergo the IAD harvest following a post-induction IAD harvest calculation. IAD blood will be collected into citrate-phosphate-dextrose-adenine 1 (CPDA-1) blood bags. All subjects will receive a volume of Hespan® equal to the volume of their IAD harvest (to a maximum of 1 liter) performed as a result of the harvest calculation (0-1200 mL inclusive). Additional volume replacement required owing to IAD \>1000mL will be performed with crystalloid, as required. Subjects will be randomized into one of two treatment arms (Hemolink™ arm or control arm) upon meeting a transfusion trigger for the first time while on CPB. Randomization will be administered centrally. Subjects will be transfused upon reaching predetermined transfusion triggers, reflecting a decrease in hemoglobin concentration and/or oxygenation:

Eligibility criteria: Inclusion Criteria:

Subjects meeting all of the following criteria are eligible for inclusion in the study:

* Written Informed Consent.
* Age 18 through 80 years, inclusive.
* Scheduled for primary CABG surgery with CPB and are candidates for IAD.
* Post-induction hemoglobin, which will allow collection of 0-1200 mL inclusive of IAD blood to achieve a target hemoglobin of 7.5 g/dL at 15 minutes on-CPB.
* For women of childbearing potential only, able to use and using a highly-effective contraceptive method from the time of study screening through week 4 - 8 post CABG surgery (follow-up visit).

Note: International Conference on Harmonization (ICH) guidelines define a highly-effective contraceptive method as one with a failure rate of less than one percent when used consistently and correctly

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

* Previous treatment with Hemolink(tm) or any other hemoglobin-based oxygen carrier.
* Participation in any clinical trial of an investigational drug, device, or medical procedure within the two months prior to enrollment, or concurrent with participation in this study.
* History of stroke with residual paralysis or of transient ischemic attacks within 6 months prior to surgery.
* Congenital coagulation disorder or treatment with Coumadin within seven days prior to surgery.
* Alcohol or drug use within the 12 months prior to enrollment, which the investigator considers abusive.
* Planned simultaneous surgery (e.g., valve repair or carotid endarterectomy).
* Emergency CABG.
* Previous surgery using sternotomy.
* Current pregnancy or nursing.
* Chronic pancreatitis with or without pancreatic insufficiency.

Any subject who is medically cleared for both the surgical procedure and the intraoperative autologous donation will be eligible for enrollment in the study.

Medical clearance requires the following:

* No current congestive heart failure, New York Heart Association class IV.
* Most recent (within 1 year of surgery) ejection fraction must not be less than or equal to 25 percent, or left ventricular function of grade 4.
* No current uncontrolled hypertension.
* No current severe pulmonary disease which will render the subject at high risk of requiring prolonged post-operative ventilation.
* No serum creatinine \> 2.0 mg/dL (177 umol/L).
* No known AST and ALT and bilirubin \> 3 times the upper limit of normal.
* No uncontrolled angina within 24 hours prior to surgery despite maximal medical treatment, and/or presence of an intraaortic balloon pump preoperatively.
* No history of transmural myocardial infarction within the five days prior to the scheduled CABG surgery.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center - San Francisco-Division of Cardiovascular Anesthesia
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center: Department of Anesthesiology
state: California
city: Sarasota
country: United States
facility: Clinical Research Center
state: Florida
city: Des Moines
country: United States
facility: Heart and Vascular Care
state: Iowa
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Englewood
country: United States
facility: Englewood Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Hospital
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina: Department of Anesthesiology
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Department of Anesthesiology
state: Ohio
city: Portland
country: United States
facility: Veterans Affairs Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Research
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Health System
state: Pennsylvania
city: Houston
country: United States
facility: Cardiovascular Anesthesia Research:Texas Heart Institute
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Medical College of Virginia: Department of Anesthesiology
state: Virginia
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital/ Vancouver General Hospital
state: British Columbia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Toronto Hospital - General Division
state: Ontario
city: Montreal
country: Canada
facility: Institut de Cardiologie de Montreal
state: Quebec
city: Ste Foy
country: Canada
facility: Hopital Laval
state: Quebec
city: London
country: United Kingdom
facility: St. Thomas Hospital: Department of Anesthesia
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
Study officials:
References:
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citation: Freilich D, Branda R, Hacker M, Leach L, Barry B, Ferris S, Hebert J. Decreased lactic acidosis and anemia after transfusion of o-raffinose cross-linked and polymerized hemoglobin in severe murine malaria. Am J Trop Med Hyg. 1999 Feb;60(2):322-8. doi: 10.4269/ajtmh.1999.60.322.
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citation: Ali AC, Mihas CC, Campbell JA. Interferences of o-raffinose cross-linked hemoglobin in three methods for serum creatinine. Clin Chem. 1997 Sep;43(9):1738-43.
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