A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery

J Thorac Cardiovasc Surg. 2004 Jan;127(1):79-86. doi: 10.1016/j.jtcvs.2003.08.024.

Abstract

Background: We performed this study to determine the dose-response of hemoglobin raffimer administered in conjunction with intraoperative autologous donation in patients undergoing coronary artery bypass grafting surgery. A secondary objective was to evaluate hemoglobin raffimer for reducing the incidence of allogeneic red blood cell transfusions.

Methods: This was a phase II, single-blind, multicenter, placebo-controlled, open-label study. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation were randomized to receive a single dose of hemoglobin raffimer or control (10% pentastarch). Patients were sequentially enrolled in a dose block of 250, 500, 750, and 1000 mL.

Results: Sixty patients received hemoglobin raffimer (n = 30) or control (n = 30). Hemoglobin raffimer was well tolerated. Most (98%) adverse events were mild or moderate in severity. There was an expected dose-dependent increase in the incidence of blood pressure increases and jaundice in hemoglobin raffimer-treated patients. In a dose-pooled analysis of hemoglobin raffimer versus control, increased blood pressure (43% vs 17%), nausea (37% vs 33%), and atrial fibrillation (37% vs 17%) were the most frequently reported adverse events. All serious adverse events were considered unrelated or unlikely to be related to study drug. No hemoglobin raffimer-treated patient required an intraoperative allogeneic red blood cell transfusion, compared with 5 (17%) pentastarch-treated patients (P =.052). This advantage of hemoglobin raffimer was maintained at 24 hours after surgery (7% vs 37%; P =.010) and up to 5 days after surgery (10% vs 47%; P =.0034).

Conclusions: Hemoglobin raffimer was not associated with any serious adverse events in patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation in a dose-response study up to 1000 mL. Hemoglobin raffimer was effective in facilitating decreased exposure or avoidance of allogeneic red blood cell transfusions when used in conjunction with intraoperative autologous donation.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Coronary Angiography
  • Coronary Artery Bypass / adverse effects
  • Coronary Artery Bypass / methods*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / surgery*
  • Dose-Response Relationship, Drug
  • Elective Surgical Procedures
  • Female
  • Follow-Up Studies
  • Hemoglobins / administration & dosage*
  • Humans
  • Intraoperative Period
  • Male
  • Maximum Tolerated Dose*
  • Middle Aged
  • Probability
  • Raffinose / administration & dosage*
  • Raffinose / analogs & derivatives*
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Single-Blind Method
  • Treatment Outcome

Substances

  • Hemoglobins
  • O-raffinose cross-linked human hemoglobin
  • Raffinose