Safety and Efficacy Study of PB127 Ultrasound Contrast Agent in Patients With Suspected Coronary Artery Disease

CSP 127-006 A Phase 3 Clinical Trial to Assess Perfusion and Obstruction Identified by Non-Invasive Technology Using PB127 Ultrasound Contrast Agent in Patients With Suspected Obstructive Coronary Arter Disease

This trial is to compare PB127 echocardiography to other heart imaging studies.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: PB127 for injectable suspension

• Study Type: Interventional
• Enrollment (Actual): 456
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Michael Morgan, MD
  • California
    • Long Beach, California, United States, 90822
      • Long Beach VA Medical Center Cardiology Division
    • San Diego, California, United States, 92103
      • University of California San Diego Division of Cardiology
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center NCIRE
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center Cardiovascular Research Institute
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • The Center for Cardiovascular Studies Kramer & Crouse Cardiology
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation Department of Cardiology
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Cardiovascular Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Sciences Center at San Antonio
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center Department of Cardiology
    • Spokane, Washington, United States, 99204
      • Northwest Cardiovascular Research Institute Spokane Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Stratum 1:

1. Able to provide written informed consent
2. Low (less than 10%) pre-test probability of CAD (Appendix D)
3. Scheduled for clinically indicated stress echocardiography or stress SPECT within the 14 days prior to or following Study Day 1 (prior to coronary angiography) or coronary angiography within the 7 days following Study Day 1
4. Technically adequate unreconstructed stress SPECT data or scheduled for clinically indicated stress SPECT within 14 days of Study Day 1 and prior to coronary angiography
5. Adequate visualization of all myocardial segments in at least one view during non-contrast echocardiography (See Section 5.3.1)
6. No evidence of a right-to-left shunt during non-contrast echocardiography

Stratum 2:

1. Able to provide written informed consent
2. Intermediate (10% to 90%) pre-test probability of CAD (Appendix D)
3. Scheduled for clinically indicated coronary angiography within the 7 days following Study Day 1
4. Technically adequate unreconstructed stress SPECT data or scheduled for stress SPECT within 14 days of Study Day 1 and prior to coronary angiography
5. Adequate visualization of all myocardial segments in at least one view during non-contrast echocardiography (See Section 5.3.1)
6. No evidence of a right-to-left shunt during non-contrast echocardiography

Stratum 3:

1. Able to provide written informed consent
2. High (greater than 90%) pre-test probability of CAD (Appendix D)
3. Scheduled for clinically indicated coronary angiography within the 7 days following Study Day 1
4. Technically adequate unreconstructed stress SPECT data or scheduled for stress SPECT within 14 days of Study Day 1 and prior to coronary angiography
5. Adequate visualization of all myocardial segments in at least one view during non-contrast echocardiography (See Section 5.3.1)
6. No evidence of a right-to-left shunt during non-contrast echocardiography

Exclusion Criteria:

1. Women who are pregnant or lactating

2. Known hypersensitivity or known contraindication to:

   1. Dipyridamole
   2. Ultrasound contrast agents (including PB127 and excipients)
   3. Blood, blood products, albumin, egg, or protein
3. Use of caffeine or xanthine containing products within the 24 hours prior to PB127 MCE
4. Previous exposure to PB127 Ultrasound Contrast Agent
5. Heart transplant
6. Known right-to-left shunt including atrial septal defect
7. Current or history of uncontrolled ventricular tachycardia
8. Current atrial fibrillation, atrial tachycardia, or atrial flutter
9. Pacemaker or defibrillator

10. Unstable cardiac status

    1. Unstable angina grade CCS Class IV severity with ongoing symptoms and/or ongoing infusion of intravenous nitroglycerin (See Appendix F)
    2. Second-degree or greater heart block
    3. Frequent (>60/hour) or symptomatic ventricular ectopics at baseline
    4. Hypertension (SPB >200 and/or DBP >110 mmHg on two consecutive readings within one hour of PB127 MCE)
    5. Hypotension (SPB <90 mmHg)
    6. Severe aortic stenosis (>100 mmHg peak transvalvar gradient or <0.6 cm2 estimated valve area)
    7. Pulmonary edema within the 7 days prior to Study Day 1
    8. Resting oxygen saturation of less than 90%
    9. Q-wave myocardial infarction within the 7 days prior to Study Day 1
    10. PTCA or CABG within the 7 days prior to Study Day 1
11. Chronic Obstructive Pulmonary Disease (COPD) or bronchospastic airway disease which, in the opinion of the Investigator, is significant enough to contraindicate dipyridamole
12. Known history of severe pulmonary hypertension characterized by estimated pulmonary artery systolic pressure of >50 mmHg
13. Use of intravenous or intracoronary contrast agent other than thallium or technetium within the 24 hours prior to Study Day 1

14. Liver disease (i.e., current or previous hepatic viral infection, chronic hepatitis) characterized by one or more of the following

    1. Current jaundice
    2. Elevated bilirubin > upper limit of normal
    3. Currently elevated hepatic enzymes > 2X upper limit of normal
15. Medical conditions or other circumstances that would significantly decrease the chances of obtaining reliable data or achieving the study objectives (i.e., drug dependence, psychiatric disorder, dementia, or associated illness), extenuating circumstances, medical conditions that make it unlikely that a patient can complete the clinical trial or follow-up evaluations, or other reasons for expected poor compliance with the Investigator's instructions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To demonstrate the non-inferiority of the diagnostic performance of PB127 MCE versus stress SPECT in the detection and/or exclusion of significant obstructive CAD as defined by QCA or qualifying clinical outcome.	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the concordance of PB127 MCE with stress SPECT in differentiating between reversible vs. fixed defects in patients with significant obstructive CAD	28 days
To compare the diagnostic performance of PB127 MCE with stress SPECT in identifying the location of stenosis as identified by coronary angiography.	28 days

Collaborators and Investigators

• Sponsor: Point Biomedical
• Investigators: Study Director: Alexander Ehlgen, MD, PhD, POINT Biomedical Corp.

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): October 1, 2003
• Study Completion (Actual): October 1, 2003

Study Registration Dates

• First Submitted: January 7, 2008
• First Submitted That Met QC Criteria: January 7, 2008
• First Posted (Estimate): January 16, 2008

Study Record Updates

• Last Update Posted (Estimate): July 3, 2008
• Last Update Submitted That Met QC Criteria: July 1, 2008
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: SPECT; angiography; Chest pain; Perfusion; Echocardiograpy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 127-006