Phase II Study To Evaluate The Safety and Efficacy of Hemoglobin Raffimer in Patients Undergoing First Time CABG Surgery

Cardiovascular Disease Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00038454
• Other study ID #: HLK-213
• Status: Suspended
• Phase: Phase 2/Phase 3
• First received: May 30, 2002
• Last updated: June 23, 2005

Study information

• Verified date: April 2003
• Source: Hemosol
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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:

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 180
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Hemolink (hemoglobin raffimer IV solution)

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Institut de Cardiologie de Montreal	Montreal	Quebec
Canada	Hopital Laval	Ste Foy	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	The Toronto Hospital - General Division	Toronto	Ontario
Canada	St. Paul's Hospital/ Vancouver General Hospital	Vancouver	British Columbia
United Kingdom	St. Thomas Hospital: Department of Anesthesia	London	England
United Kingdom	Southampton General Hospital	Southampton	England
United States	University of North Carolina: Department of Anesthesiology	Chapel Hill	North Carolina
United States	The Ohio State University Department of Anesthesiology	Columbus	Ohio
United States	Heart and Vascular Care	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Englewood Hospital	Englewood	New Jersey
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Cardiovascular Anesthesia Research:Texas Heart Institute	Houston	Texas
United States	Robert Wood Johnson Hospital	New Brunswick	New Jersey
United States	Mount Sinai Medical Center	New York	New York
United States	UPMC Health System	Pittsburgh	Pennsylvania
United States	Legacy Research	Portland	Oregon
United States	Veterans Affairs Medical Center	Portland	Oregon
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Medical College of Virginia: Department of Anesthesiology	Richmond	Virginia
United States	Kaiser Permanente Medical Center - San Francisco-Division of Cardiovascular Anesthesia	San Francisco	California
United States	Clinical Research Center	Sarasota	Florida
United States	Washington University	St. Louis	Missouri
United States	Stanford University Medical Center: Department of Anesthesiology	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Hemosol

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

References & Publications (24)

Ali AC, Campbell JA. Interference of o-raffinose cross-linked hemoglobin with routine Hitachi 717 assays. Clin Chem. 1997 Sep;43(9):1794-6. — View 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. — View Citation

Arnoldo BD, Minei JP. Potential of hemoglobin-based oxygen carriers in trauma patients. Curr Opin Crit Care. 2001 Dec;7(6):431-6. Review. — View Citation

Baines AD, Christoff B, Wicks D, Wiffen D, Pliura D. Cross-linked hemoglobin increases fractional reabsorption and GFR in hypoxic isolated perfused rat kidneys. Am J Physiol. 1995 Nov;269(5 Pt 2):F628-36. — View Citation

Balion CM, Champagne PA, Ali AC. Evaluation of HemogloBind for removal of o-raffinose cross-linked hemoglobin (Hemolink) from serum. Clin Chem. 1997 Sep;43(9):1796-7. — View Citation

Carmichael FJ, Ali AC, Campbell JA, Langlois SF, Biro GP, Willan AR, Pierce CH, Greenburg AG. A phase I study of oxidized raffinose cross-linked human hemoglobin. Crit Care Med. 2000 Jul;28(7):2283-92. — View Citation

Caron A, Malfatti E, Aguejouf O, Faivre-Fiorina B, Menu P. Vasoconstrictive response of rat mesenteric arterioles following infusion of cross-linked, polymerized, and conjugated hemoglobin solutions. Artif Cells Blood Substit Immobil Biotechnol. 2001 Jan;29(1):19-30. — View Citation

Caron A, Menu P, Faivre-Fiorina B, Labrude P, Alayash AI, Vigneron C. Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits. J Appl Physiol (1985). 1999 Feb;86(2):541-8. — View Citation

Cheng DC. Safety and efficacy of o-raffinose cross-linked human hemoglobin (Hemolink) in cardiac surgery. Can J Anaesth. 2001 Apr;48(4 Suppl):S41-8. Review. — View Citation

Cohn SM. Blood substitutes in surgery. Surgery. 2000 Jun;127(6):599-602. Review. — View 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. — View Citation

Glaser V. Fake blood market gets hemoglobin transfusion from reticulocytes. Nat Biotechnol. 1998 Aug;16(8):709. — View Citation

Jahr JS, Lurie F, Driessen B, Davis JA, Gosselin R, Gunther RA. The HemoCue, a point of care B-hemoglobin photometer, measures hemoglobin concentrations accurately when mixed in vitro with canine plasma and three hemoglobin-based oxygen carriers (HBOC). Can J Anaesth. 2002 Mar;49(3):243-8. — View Citation

Kerger H, Tsai AG, Saltzman DJ, Winslow RM, Intaglietta M. Fluid resuscitation with O2 vs. non-O2 carriers after 2 h of hemorrhagic shock in conscious hamsters. Am J Physiol. 1997 Jan;272(1 Pt 2):H525-37. — View Citation

Kingma JG Jr, Sandhu R, Hamelin ND, Gendron D, Trudel Y, Bosa M, Stewart R, Fargey MB, Biro GP. The effects of hemodilution with Hemolink upon hemodynamics and blood flow distribution in anesthetized dogs. Artif Cells Blood Substit Immobil Biotechnol. 2001 Nov;29(6):465-81. Corrected and republished in: Artif Cells Blood Substit Immobil Biotechnol. 2002 Mar;30(2):137-54. — View Citation

Lieberthal W, Fuhro R, Andry C, Valeri CR. Effects of hemoglobin-based oxygen-carrying solutions in anesthetized rats with acute ischemic renal failure. J Lab Clin Med. 2000 Jan;135(1):73-81. — View Citation

Lieberthal W, Fuhro R, Freedman JE, Toolan G, Loscalzo J, Valeri CR. O-raffinose cross-linking markedly reduces systemic and renal vasoconstrictor effects of unmodified human hemoglobin. J Pharmacol Exp Ther. 1999 Mar;288(3):1278-87. — View Citation

Macdonald RL, Zhang J, Weir B, Marton LS, Wollman R. Adenosine triphosphate causes vasospasm of the rat femoral artery. Neurosurgery. 1998 Apr;42(4):825-32; discussion 832-3. — View Citation

Ning J, Wong LT, Christoff B, Carmichael FJ, Biro GP. Haemodynamic response following a 10% topload infusion of HemolinkTM in conscious, anaesthetized and treated spontaneously hypertensive rats. Transfus Med. 2000 Mar;10(1):13-22. — View Citation

Scatena R, Giardina B. O-raffinose-polymerised haemoglobin. A biochemical and pharmacological profile of an oxygen carrier. Expert Opin Biol Ther. 2001 Jan;1(1):121-7. Review. — View Citation

Topfer LA, Hailey D. Oxygen carriers ("blood substitutes"). Issues Emerg Health Technol. 2001 Jul;(21):1-6. — View Citation

Toussaint M, Latger-Cannard V, Caron A, Lecompte T, Stoltz JF, Vigneron C, Menu P. Effects of three Hb-based oxygen-carrying solutions on neutrophil activation in vitro: quantitative measurement of the expression of adherence receptors. Transfusion. 2001 Feb;41(2):226-31. — View Citation

Wong LT, Er SS, Ning J, Christoff B, Carmichael FJ. Hemolink-induced effects on intestinal motor function and attenuation of these effects by selected agents. Artif Cells Blood Substit Immobil Biotechnol. 1998 Nov;26(5-6):529-48. — View Citation

Xue S, Paterson W, Valdez D, Miller D, Christoff B, Wong LT, Diamant NE. Effect of an o-raffinose cross-linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function. Neurogastroenterol Motil. 1999 Dec;11(6):421-30. — View Citation

* Note: There are 24 references in all — Click here to view all references