Not Signed In -
Hemoglobin |
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Clinical Trial: Phase II Study To Evaluate The Safety and Efficacy of Hemoglobin Raffimer in Patients Undergoing First Time CABG Surgery
This study has been suspended.
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Purpose
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
| Condition | Treatment or Intervention | Phase |
|---|---|---|
| Cardiovascular Disease | Drug: Hemolink (hemoglobin raffimer IV solution) | Phase II Phase III |
MedlinePlus related topics: Heart Diseases; Vascular Diseases
Study Type: Interventional
Study Design: Treatment, Randomized, Single Blind, Placebo Control, Single Group Assignment, Safety/Efficacy Study
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
Expected Total Enrollment: 180
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
Ages Eligible for Study: 18 Years - 80 Years, Genders Eligible for Study: Both
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.
Location Information
California
Stanford University Medical Center: Department of Anesthesiology, Stanford, California, 94305, United States
Kaiser Permanente Medical Center - San Francisco-Division of Cardiovascular Anesthesia, San Francisco, California, 94115, United States
Florida
Clinical Research Center, Sarasota, Florida, 34239, United States
Iowa
Heart and Vascular Care, Des Moines, Iowa, 50314, United States
Michigan
Henry Ford Hospital, Detroit, Michigan, 48202, United States
Missouri
Washington University, St. Louis, Missouri, 63110, United States
New Jersey
Robert Wood Johnson Hospital, New Brunswick, New Jersey, 08901, United States
Englewood Hospital, Englewood, New Jersey, 07361, United States
New York
Mount Sinai Medical Center, New York, New York, 10029-6574, United States
North Carolina
Duke University Medical Center, Durham, North Carolina, 27710, United States
University of North Carolina: Department of Anesthesiology, Chapel Hill, North Carolina, 27514, United States
Ohio
The Ohio State University Department of Anesthesiology, Columbus, Ohio, 43210, United States
Oregon
Veterans Affairs Medical Center, Portland, Oregon, 97201, United States
Legacy Research, Portland, Oregon, 97232, United States
Pennsylvania
UPMC Health System, Pittsburgh, Pennsylvania, 15213, United States
Texas
Cardiovascular Anesthesia Research:Texas Heart Institute, Houston, Texas, 77225-0345, United States
Virginia
Inova Fairfax Hospital, Falls Church, Virginia, 55042-3300, United States
Medical College of Virginia: Department of Anesthesiology, Richmond, Virginia, 23298-0695, United States
McGuire VA Medical Center, Richmond, Virginia, 23249, United States
Canada, Alberta
Foothills Medical Centre, Calgary, Alberta, T2N 2T9, Canada
Canada, British Columbia
St. Paul's Hospital/ Vancouver General Hospital, Vancouver, British Columbia, VZ 4E3, Canada
Canada, Ontario
St. Michael's Hospital, Toronto, Ontario, M5B 1W8, Canada
The Toronto Hospital - General Division, Toronto, Ontario, M5G 2C4, Canada
Kingston General Hospital, Kingston, Ontario, K7L 2V7, Canada
Canada, Quebec
Hopital Laval, Ste Foy, Quebec, G1V 4G5, Canada
Institut de Cardiologie de Montreal, Montreal, Quebec, H1T 1C8, Canada
United Kingdom, England
Southampton General Hospital, Southampton, England, SO16 6YD, United Kingdom
St. Thomas Hospital: Department of Anesthesia, London, England, SE1 7EH, United Kingdom
More Information
Publications
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.
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.
Topfer LA, Hailey D. Oxygen carriers ("blood substitutes"). Issues Emerg Health Technol. 2001 Jul;(21):1-6.
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.
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.
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.
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.
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.
Cohn SM. Blood substitutes in surgery. Surgery. 2000 Jun;127(6):599-602. Review. No abstract available.
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.
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.
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.
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.
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.
Glaser V. Fake blood market gets hemoglobin transfusion from reticulocytes. Nat Biotechnol. 1998 Aug;16(8):709. No abstract available.
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.
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.
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.
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.
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.
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.
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.
Arnoldo BD, Minei JP. Potential of hemoglobin-based oxygen carriers in trauma patients. Curr Opin Crit Care. 2001 Dec;7(6):431-6. Review.
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. 1999 Feb;86(2):541-8.
Record last reviewed: April 2003
Last Updated: October 13, 2004
Record first received: May 30, 2002
ClinicalTrials.gov Identifier: NCT00038454
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08
Source: ClinicalTrials.gov
Cache Date: April 9, 2005
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