Pilot Study of Hemoglobin Based Oxygen Therapeutics in Elective Coronary Revascularization

Myocardial Infarction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00317512
• Other study ID #: COR-0001
• Status: Completed
• Phase: Phase 2
• First received: April 21, 2006
• Last updated: May 15, 2008
• Start date: December 2003
• Est. completion date: July 2007

Study information

• Verified date: May 2008
• Source: Biopure Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPGermany: Federal Institute for Drugs and Medical DevicesNetherlands: Dutch Health Care Inspectorate
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 2007
• Est. primary completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Unstable
• Infarction
• Myocardial Infarction
• Unstable Angina

Intervention

Procedure:
• Percutaneous Coronary Revascularization

Drug:
• Hemoglobin-Based Oxygen Carrier-201 (HBOC-201)

• Voluven

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biopure Corporation

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands, 

References & Publications (1)

Serruys PW, Vranckx P, Slagboom T, Regar E, Meliga E, de Winter RJ, Heyndrickx G, Schuler G, van Remortel EA, Dubé GP, Symons J. Haemodynamic effects, safety, and tolerability of haemoglobin-based oxygen carrier-201 in patients undergoing PCI for CAD. Eur — View Citation

Outcome

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