Clinical trial NCT00317512: Pilot Study of Hemoglobin Based Oxygen Therapeutics in Elective Coronary Revascularization
Official title: A Multi-Center,Randomized,Double-Blind,Placebo-Controlled,Dose Finding Pilot Study, to Evaluate Safety/Feasibility of HBOC-201 in Elective Percutaneous Coronary Revascularization of Subjects With Acute Coronary Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Angina Pectoris
Unstable Angina
Myocardial Infarction
Keywords: Hemoglobin Based Oxygen carrier
HBOC 201
Percutaneous Revascularization
Percutaneous Coronary Intervention
Non ST-segment Elevation Myocardial Infarction
Tissue Oxygenation
Transluminal Percutaneous Coronary Angioplasty
Lead sponsor: Biopure Corporation
Sponsor class: INDUSTRY
First posted: 2006-04-25
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and feasibility of a novel oxygen carrying solution, HBOC-201, in the setting of PCI for Acute Coronary Syndromes from randomization til hospital discharge.

Detailed description: Acute coronary syndromes are due to an acute or subacute primary reduction of myocardial oxygen supply provoked by disruption of an atherosclerotic plaque associated with inflammation, thrombosis, vasoconstriction and microembolization. Occlusive thrombosis superimposed on a ruptured atheroma in an epicardial coronary artery is firmly established as the immediate cause of an acute ST-segment Elevation Myocardial Infarction (STEMI). Rapid restoration of blood flow (oxygen supply) to jeopardized myocardium limits necrosis and reduces mortality. This can be accomplished medically with a thrombolytic agent, or mechanically, with so-called primary balloon angioplasty or stenting. Primary percutaneous coronary intervention (PCI) has become the preferred therapy for STEMI in most developed countries.

HBOC-201 is a solution belonging to a new class of biologic oxygen therapeutics, hemoglobin based oxygen carriers. HBOC-201 is a crosslinked and glutaraldehyde-polymerized hemoglobin (Hb) extracted from isolated bovine red blood cells. On a gram-for-gram basis, HBOC-201 was calculated to be approximately three times more potent than stored fresh red blood cell hemoglobin at restoring baseline tissue oxygenation following severe acute anemia. Evaluation of this Hemoglobin Based Oxygen Carrier has been undertaken in 57 preclinical studies and 21 human clinical trials. The compound is under review by the US FDA and has been approved in the Republic of South Africa. However, HBOC-201 has not yet been evaluated in the setting of this disease (narrowing of a coronary artery).

Biopure will be studying the safety and feasibility of HBOC-201 in patients with typical symptoms of Unstable Angina or Non ST-segment Elevation Myocardial Infarction eligible to undergo invasive revascularization through a PCI procedure.

Eligibility criteria: Inclusion Criteria:

* Written informed consent provided before initiation of any study-related procedure, and before any pre-procedural sedation, and agreement to comply with all protocol-specified procedures
* Acute Coronary Syndrome (Stable and unstable angina or non ST segment Elevation Myocardial Infarction (UA/non-STEMI) \[Braunwald class I-III Class B\], Appendix 1).
* Single vessel disease of the Left Coronary Artery (LCA)
* One vessel disease of the Right Coronary Artery (RCA)
* Have a single de novo lesion
* Older than 18 years and younger than 75 years of age
* Eligible to undergo PCI on the target vessel

Exclusion Criteria:

* Previous Q-wave myocardial infarction
* Congestive heart failure with Left ventricular Ejection Fraction \<35%
* Confirmed pregnancy
* Anemia to a hemoglobin level \<8.5g/dl
* Systemic mastocytosis
* History of known haemorrhagic stroke at any time or any stroke less than or equal to 30 days prior to randomization
* Severe hypertension (\>180/110mmHG) not adequately controlled by antihypertensive therapy at time of study entry
* Need for mechanical ventilation
* Renal impairment: Creatinine \> 1.6mg/dl
* Known history of COPD with FEV 1s \< 1.0 liter
* Contra-indications to the use of adenosine, i.e.History of bronchospasm and/or ongoing therapy with theophylline derivatives, \>1 degree atrioventricular block in the absence of a functioning electronic pacemaker and treatment with dipyridamole within the prior 24 hours
* Patients with significant hemodynamic compromise and/or cardiogenic shock requiring inotropic or pressor support or pulmonary edema
* History of or clinical documentation of severe aortic/mitral valve stenosis, significant aortic valve insufficiency
* Participation in another trial with an investigational drug or device (of other investigations) including the follow-up period, within the last 30 days before enrollment
* Inability or unwillingness to perform 30 day follow up
* Concomitant disease that interferes with prognosis (life expectancy of less than or equal to 6 months
* Contra-indications to standard drugs for coronary intervention and coronary heart disease: aspirin, heparin, low molecular weight heparin, clopidogrel, contrast dye
* Patient weight \> 110kg

Primary outcomes:
measure: Safety
measure: In hospital thrombotic events
measure: Anaphylactic reactions
measure: Inflammatory reactions
measure: Substantial changes to systemic & coronary hemodynamics
measure: Circulatory overload
measure: Renal dysfunction
measure: Untoward drug interaction effects
measure: substantial changes in laboratory parameters
measure: Life threatening cardiac arrhythmias
measure: Other adverse events
measure: Feasibility:
measure: Number of subjects requiring premature discontinuation of study drug for clinical or logistical reasons
Secondary outcomes:
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Site # 5 Onze Lieve Vrouw Ziekenhuis (OLVZ)
city: Antwerpen
country: Belgium
facility: Site # 6 Antwerpen
city: Leipzig
country: Germany
facility: Site # 2 Herzzentrum
city: Amsterdam
country: Netherlands
facility: Site # 3 OLVG Amsterdam
city: Amsterdam
country: Netherlands
facility: Site # 4 Academisch Medisch Centrum (AMC)
city: Rotterdam
country: Netherlands
facility: Site # 1 Erasmus Medical Center
Study officials:
affiliation: University Medical Center Rotterdam
name: P W Serruys, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Serruys PW, Vranckx P, Slagboom T, Regar E, Meliga E, de Winter RJ, Heyndrickx G, Schuler G, van Remortel EA, Dube GP, Symons J. Haemodynamic effects, safety, and tolerability of haemoglobin-based oxygen carrier-201 in patients undergoing PCI for CAD. EuroIntervention. 2008 Mar;3(5):600-9. doi: 10.4244/eijv3i5a108.