Safety and Efficacy Study of PB127 Ultrasound Contrast Agent for Diagnosis of Coronary Artery Disease (POINT II)

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 Artery Disease II

The purpose of this study is to determine if the use of PB127 with cardiac ultrasound assists in the diagnosis or exclusion of coronary artery disease.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: PB127 for Injectable Suspension

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Saver Heart Clinic
  • California
    • Burlingame, California, United States, 94010
      • Cardiovascular Associates of the Peninsula
    • Long Beach, California, United States, 90822
      • Long Beach VA Medical Center Cardiology Division
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Division of Cardiology
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • 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
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Connecticut Clinical Research
  • Delaware
    • Newark, Delaware, United States, 19713
      • Alfieri Cardiology
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center Cardiovascular Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Kansas
    • Overland Park, Kansas, United States, 66209
      • Midwest Cardiology Associates
    • Shawnee Mission, Kansas, United States, 66204
      • The Center for Cardiovascular Studies Kramer & Crouse Cardiology
  • Kentucky
    • Paducah, Kentucky, United States, 42001
      • Western Baptist Hospital The Heart Group
  • Maine
    • Auburn, Maine, United States, 04210
      • Androscoggin Cardiovascular Associates
    • South Portland, Maine, United States, 04106
      • Maine Cardiology Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hosptial
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Department of Cardiology
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Cardiovascular Consultants
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Medical Center
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10025
      • St. Luke's Roosevelt Hospital Echocardiography Lab
    • Stonybrook, New York, United States, 11794
      • Stonybrook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • High Point, North Carolina, United States, 27262
      • Carolina Cardiology Associates
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation Department of Cardiology
    • Columbus, Ohio, United States, 43210
      • Ohio State University College of Medicine and Public Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • University of Oklahoma Health Sciences Center VA Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Cardiovascular Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Heart
    • Austin, Texas, United States, 78701
      • Seton Healthcare Network Brackenridge Hospital
    • Fort Worth, Texas, United States, 76104
      • Consultants in Cardiology
    • Galveston, Texas, United States, 77555
      • University of Texas Division of Cardiology
    • Houston, Texas, United States, 77030
      • Methodist DeBakery Heart Center Cardiovascular Imaging Institute
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center Memorial Hermann Heart & Vascular Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center Department of Cardiology
    • Spokane, Washington, United States, 99204
      • Heart Clinics Northwest
    • Spokane, Washington, United States, 99204
      • Northwest Cardiovascular Research Institute Spokane Cardiology
    • Spokane, Washington, United States, 99204
      • Inland 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

1. 18 years old or older and able to provide written informed consent;
2. All subjects must be scheduled for or have undergone SPECT within 28 days prior to or following Study Day 1
3. Subjects with very low/low pre-test probability of coronary artery disease must consent to participate in the extension trial 127-014-A
4. Subjects with very low/low pre-test probability of coronary artery disease must not have a current diagnosis of obstructive CAD on angiogram or prior MI
5. Subjects with very low/low pre-test probability of coronary artery disease with a current diagnosis of obstructive CAD on angiogram or prior MI may be enrolled into Stratum 2
6. Subjects with intermediate or high pre-test probability of coronary artery disease must be scheduled for coronary angiography within the 28 days following Study Day 1
7. Sinus rhythm at the time of the study procedure
8. Adequate visualization of myocardial segments
9. Appropriate candidate for stress testing according to ACC/AHA Guidelines for Exercise Testing

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 Study Day 1
4. Previous exposure to PB127 Ultrasound Contrast Agent
5. Major surgery within 7 days prior to Study Day 1 (requiring general anesthesia and/or overnight stay)
6. Heart transplant or history of CABG
7. Known hemodynamically significant or symptomatic right-to-left shunt (including shunts that are associated with prior TIAs or strokes)
8. Recent history of sustained ventricular tachycardia
9. Pacemaker or defibrillator

10. Unstable cardiac status

    1. Unstable angina grade CCS Class IV severity (any physical activity causes limiting symptoms; symptoms may be present at rest in a patient with prior exertional angina) with ongoing symptoms and/or ongoing infusion of intravenous nitroglycerin
    2. Decompensated heart failure
    3. Second-degree or greater heart block, sick sinus syndrome
    4. Frequent (>60/hour) or symptomatic ventricular ectopics at baseline
    5. Hypertension (SBP >200 and/or DBP >110 mmHg on two consecutive readings within one hour of PB127 MPE)
    6. Hypotension (SBP <90 mmHg)
    7. Severe aortic stenosis (>40 mmHg mean gradient or <0.6 cm2/m2 valve area index)
    8. Pulmonary edema within the 7 days prior to Study Day 1
    9. Resting oxygen saturation of less than 90% on room air
11. Myocardial infarction or cerebral vascular accident / transient ischemic attack within the 28 days prior to Study Day 1
12. Chronic Obstructive Pulmonary Disease (COPD) or bronchospastic airway disease, which in the opinion of the Investigator, is significant enough to contraindicate dipyridamole
13. Known history of severe pulmonary hypertension characterized by estimated pulmonary artery systolic pressure of >50 mmHg

14. Liver disease 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
    4. Current or previous hepatic viral infection (not including hepatitis A)
    5. Chronic hepatitis
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 or 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 clinical 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 evaluate the diagnostic performance of PB127 MPE for the detection and/or exclusion of significant obstructive coronary artery disease as defined by qualitative coronary angiography or qualifying clinical outcome	72 hours, 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the diagnostic performance of PB127 MPE to SPECT for the detection and/or exclusion of significant obstructive coronary artery disease.	72 hours, 6 months
To assess the concordance of PB127 MPE with SPECT in the differentiation of defect type (fixed versus reversible) in patients with significant obstructive CAD.	72 hours, 6 months
To evaluate the diagnostic performance characteristics of PB127 MPE for identifying the location of significant obstructive CAD as defined by quantitative coronary angiography	72 hours
To assess the change in diagnostic certainty when PB127 MPE and relevant clinical information are combined over relevant clinical information alone.	72 hours, 6 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 20, 2007
• First Posted (Estimate): January 2, 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: chest pain; ultrasound; coronary artery disease; SPECT; heart disease; perfusion; echocardiogram; angiogram
• 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: 127-014