Pilot Study of Hemoglobin Based Oxygen Therapeutics in Elective Coronary Revascularization

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Angina Pectoris, Unstable Angina, Myocardial Infarction

Intervention / Treatment
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* Procedure: Percutaneous Coronary Revascularization
* Drug: Hemoglobin-Based Oxygen Carrier-201 (HBOC-201)
* Drug: Voluven


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Voluven will be administered at 7.7 ml/min over 15 minutes,followed by Voluven at 7.7 ml/min over 15 minutes | Procedure: Percutaneous Coronary Revascularization<br> <br> Drug: Voluven<br> <br> |
| Active Comparator: 2<br>HBOC-201 will be administered at 7.7 ml/min over 15 minutes,followed by Voluven at 7.7 ml/min over 15 minutes | Procedure: Percutaneous Coronary Revascularization<br> <br> Drug: Hemoglobin-Based Oxygen Carrier-201 (HBOC-201)<br> <br> Drug: Voluven<br> <br> |
| Experimental: 3<br>HBOC-201 will be administered at 7.7 ml/min over 15 minutes,followed by HBOC-201 at 7.7 ml/min over 15 minutes | Procedure: Percutaneous Coronary Revascularization<br> <br> Drug: Hemoglobin-Based Oxygen Carrier-201 (HBOC-201)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| In hospital thrombotic events |  |  | 
| Anaphylactic reactions |  |  | 
| Inflammatory reactions |  |  | 
| Substantial changes to systemic & coronary hemodynamics |  |  | 
| Circulatory overload |  |  | 
| Renal dysfunction |  |  | 
| Untoward drug interaction effects |  |  | 
| substantial changes in laboratory parameters |  |  | 
| Life threatening cardiac arrhythmias |  |  | 
| Other adverse events |  |  | 
| Feasibility: |  |  | 
| Number of subjects requiring premature discontinuation of study drug for clinical or logistical reasons |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemoglobin Based Oxygen carrier, HBOC 201, Percutaneous Revascularization, Percutaneous Coronary Intervention, Non ST-segment Elevation Myocardial Infarction, Tissue Oxygenation, Transluminal Percutaneous Coronary Angioplasty