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

NCT00038454 | Suspended Phase 2

• 1 other identifier: HLK-213
• Study Type: interventional
• Target: 180
• Locations: 3 countries
• Sites: 28

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

Conditions

Cardiovascular Disease

Keywords

Oxygen Therapeutics; CABG; Transfusion

Interventions

Hemolink (hemoglobin raffimer IV solution) DRUG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hemosol: lead

Study Sites (28)

Kaiser Permanente Medical Center - San Francisco-Division of Cardiovascular Anesthesia

San Francisco, California, 94115, United States

Location

Stanford University Medical Center: Department of Anesthesiology

Stanford, California, 94305, United States

Location

Clinical Research Center

Sarasota, Florida, 34239, United States

Location

Heart and Vascular Care

Des Moines, Iowa, 50314, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Englewood Hospital

Englewood, New Jersey, 07361, United States

Location

Robert Wood Johnson Hospital

New Brunswick, New Jersey, 08901, United States

Location

Mount Sinai Medical Center

New York, New York, 10029-6574, United States

Location

University of North Carolina: Department of Anesthesiology

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University Department of Anesthesiology

Columbus, Ohio, 43210, United States

Location

Veterans Affairs Medical Center

Portland, Oregon, 97201, United States

Location

Legacy Research

Portland, Oregon, 97232, United States

Location

UPMC Health System

Pittsburgh, Pennsylvania, 15213, United States

Location

Cardiovascular Anesthesia Research:Texas Heart Institute

Houston, Texas, 77225-0345, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 55042-3300, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Medical College of Virginia: Department of Anesthesiology

Richmond, Virginia, 23298-0695, United States

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

St. Paul's Hospital/ Vancouver General Hospital

Vancouver, British Columbia, VZ 4E3, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

The Toronto Hospital - General Division

Toronto, Ontario, M5G 2C4, Canada

Location

Institut de Cardiologie de Montreal

Montreal, Quebec, H1T 1C8, Canada

Location

Hopital Laval

Ste Foy, Quebec, G1V 4G5, Canada

Location

St. Thomas Hospital: Department of Anesthesia

London, England, SE1 7EH, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Related Publications (24)

• 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. doi: 10.1007/BF03020522.

  PMID: 11861341 BACKGROUND

• 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. doi: 10.1081/bio-100108551.

  PMID: 11795632 BACKGROUND

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

  PMID: 11776287 BACKGROUND

• 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. doi: 10.1517/14712598.1.1.121.

  PMID: 11727541 BACKGROUND

• 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.

  PMID: 11336436 BACKGROUND

• 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. doi: 10.1081/bio-100001253.

  PMID: 11280681 BACKGROUND

• 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. doi: 10.1046/j.1537-2995.2001.41020226.x.

  PMID: 11239227 BACKGROUND

• 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. doi: 10.1097/00003246-200007000-00017.

  PMID: 10921554 BACKGROUND

• Cohn SM. Blood substitutes in surgery. Surgery. 2000 Jun;127(6):599-602. doi: 10.1067/msy.2000.106462. No abstract available.

  PMID: 10840352 BACKGROUND

• 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. doi: 10.1046/j.1365-3148.2000.00225.x.

  PMID: 10760199 BACKGROUND

• 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. doi: 10.1016/s0022-2143(00)70023-0.

  PMID: 10638697 BACKGROUND

• 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. doi: 10.1046/j.1365-2982.1999.00171.x.

  PMID: 10583849 BACKGROUND

• 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.

  PMID: 10072160 BACKGROUND

• 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.

  PMID: 10027869 BACKGROUND

• Glaser V. Fake blood market gets hemoglobin transfusion from reticulocytes. Nat Biotechnol. 1998 Aug;16(8):709. doi: 10.1038/nbt0898-709. No abstract available.

  PMID: 9702757 BACKGROUND

• 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. doi: 10.1097/00006123-199804000-00082.

  PMID: 9574647 BACKGROUND

• 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. No abstract available.

  PMID: 9299985 BACKGROUND

• 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.

  PMID: 9299969 BACKGROUND

• 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. doi: 10.1152/ajpheart.1997.272.1.H525.

  PMID: 9038975 BACKGROUND

• 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. doi: 10.1152/ajprenal.1995.269.5.F628.

  PMID: 7503228 BACKGROUND

• 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. doi: 10.3109/10731199809117473.

  PMID: 9844719 BACKGROUND

• Ali AC, Campbell JA. Interference of o-raffinose cross-linked hemoglobin with routine Hitachi 717 assays. Clin Chem. 1997 Sep;43(9):1794-6. No abstract available.

  PMID: 9299984 BACKGROUND

• Arnoldo BD, Minei JP. Potential of hemoglobin-based oxygen carriers in trauma patients. Curr Opin Crit Care. 2001 Dec;7(6):431-6. doi: 10.1097/00075198-200112000-00010.

  PMID: 11805546 BACKGROUND

• 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. doi: 10.1152/jappl.1999.86.2.541.

  PMID: 9931189 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

O-raffinose cross-linked human hemoglobin

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 30, 2002
• First Posted: May 31, 2002
• Last Updated: June 24, 2005

Record last verified: 2003-04

Locations

GB (2); CA (7); US (19)