Pilot Study of Hemoglobin Based Oxygen Therapeutics in Elective Coronary Revascularization - Full Text View

Sponsored by:	Biopure Corporation
Information provided by:	Biopure Corporation
ClinicalTrials.gov Identifier:	NCT00317512

Purpose

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.

Condition	Intervention	Phase
Angina Pectoris Unstable Angina Myocardial Infarction	Procedure: Percutaneous Coronary Revascularization Drug: Hemoglobin-Based Oxygen Carrier-201 (HBOC-201) Drug: Voluven	Phase II

MedlinePlus related topics: Angina Heart Attack

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Factorial Assignment, Safety/Efficacy Study
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

Further study details as provided by Biopure Corporation:

Primary Outcome Measures:

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

Enrollment:	45
Study Start Date:	December 2003
Study Completion Date:	July 2007
Primary Completion Date:	April 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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 Drug: Voluven
2: Active Comparator 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 Drug: Hemoglobin-Based Oxygen Carrier-201 (HBOC-201) Drug: Voluven
3: Experimental 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 Drug: Hemoglobin-Based Oxygen Carrier-201 (HBOC-201)

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

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317512

Locations

Belgium
Site # 5 Onze Lieve Vrouw Ziekenhuis (OLVZ)
Aalst, Belgium
Site # 6 Antwerpen
Antwerpen, Belgium
Germany
Site # 2 Herzzentrum
Leipzig, Germany
Netherlands
Site # 4 Academisch Medisch Centrum (AMC)
Amsterdam, Netherlands
Site # 3 OLVG Amsterdam
Amsterdam, Netherlands
Site # 1 Erasmus Medical Center
Rotterdam, Netherlands

Sponsors and Collaborators

Biopure Corporation

Investigators

Principal Investigator:

P W Serruys, Professor

University Medical Center Rotterdam

More Information

Publications of Results:

Serruys PW, Vranckx P, Slagboom Tet al. Hemodynamic effects, safety, and tolerability of hemoglobin-based oxygen carrier-201 (HBOC-201) in patients undergoing PCI for CAD. EuroIntervention Journal. 3: 600-609, 2008

Responsible Party:	Biopure Corporation ( Biopure Corporation )
Study ID Numbers:	COR-0001
Study First Received:	April 21, 2006
Last Updated:	May 15, 2008
ClinicalTrials.gov Identifier:	NCT00317512
Health Authority:	Belgium: Directorate general for the protection of Public health: Medicines; Germany: Federal Institute for Drugs and Medical Devices; Netherlands: Dutch Health Care Inspectorate

Keywords provided by Biopure Corporation:

Hemoglobin Based Oxygen carrier
HBOC 201
Percutaneous Revascularization
Percutaneous Coronary Intervention

Non ST-segment Elevation Myocardial Infarction
Tissue Oxygenation
Transluminal Percutaneous Coronary Angioplasty

Study placed in the following topic categories:

Heart Diseases
Myocardial Ischemia
Angina Pectoris
Vascular Diseases
HBOC 201
Pain
Ischemia

Chest Pain
Signs and Symptoms
Necrosis
Acute Coronary Syndrome
Infarction
Myocardial Infarction
Angina, Unstable

Additional relevant MeSH terms:

Pathologic Processes
Therapeutic Uses
Hematologic Agents

Blood Substitutes
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009