title: Haemodynamic effects, safety, and tolerability of haemoglobin-based oxygen carrier-201 in patients undergoing PCI for CAD.
abstract: OBJECTIVE
  Haemoglobin based oxygen carriers (HBOCs) are considered in the treatment of patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). In light of their potential vasopressor and colloidal properties, their effect on coronary physiology, safety and tolerability needs to be established.
  
  
  RESULTS
  In this phase II pilot trial, 45 patients were randomly assigned, (1:1:1) to double blind treatment with a 30 minute intravenous (IV) infusion of either 15 or 30 g of HBOC-201, compared to an equivalent volume of non-oxygen carrier colloid control. Systemic, pulmonary, and coronary haemodynamics were studied during this infusion period. IV HBOC-201 administration produced an increase in systolic blood pressure (SBP), pulmonary capillary wedge pressure and calculated systemic vascular resistance (SVR) and a concomitant decrease in cardiac output (CO); there was a decrease in mixed venous saturation (SVO2) following IV HBOC-201. The left ventricular stroke work index (LVSWI) was not altered by HBOC-201 treatment. Of note, no coronary vasoconstriction was observed, nor were there significant changes in resting average peak velocity (APV), coronary-artery diameter, volumetric coronary blood flow, or coronary vascular resistance. The percentage of patients with adverse events did not differ between the HBOC-201 treated and control groups (76% vs. 63%, respectively, P=0.49). Seven serious adverse events (SAE) occurred in six patients in the treatment group and two in two patients in the control group. Only one SAE (hypertension) was judged HBOC-201 related. Patients in both the HBOC-201 and control group had a similar incidence of increased liver alanine transaminase (31% vs 31%, respectively, NS); 10% of the patients in the HBOC-201 group had increases greater than three times the upper limit of normal. Differential increases were noticed in some inflammatory markers (IL-6, CRP) 18-24 hours after infusion between the HBOC-201 arms and the control group.
  
  
  CONCLUSIONS
  No compromise in the coronary blood flow or LVSWI was observed despite HBOC-201's known vasoactive effects. One SAE was adjudicated as "drug related" and fully resolved. The clinical relevance of the differential rise in certain biochemical markers and the adverse effects of plasma haemoglobin in the context of ACS needs further investigation.
authors.affiliation: Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Pascal
authors.initials: P
authors.lastname: Vranckx
authors.forename: Ton
authors.initials: T
authors.lastname: Slagboom
authors.forename: Evelyn
authors.initials: E
authors.lastname: Regar
authors.forename: Emanuele
authors.initials: E
authors.lastname: Meliga
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: Guy
authors.initials: G
authors.lastname: Heyndrickx
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Eric Am
authors.initials: EA
authors.lastname: van Remortel
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Dubé
authors.forename: Janette
authors.initials: J
authors.lastname: Symons