Clinical trial NCT00584896: Safety and Efficacy Study of PB127 Ultrasound Contrast Agent for Diagnosis of Coronary Artery Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronary Artery Disease
Keywords: heart disease
coronary artery disease
echocardiogram
ultrasound
angiogram
SPECT
chest pain
perfusion
Lead sponsor: Point Biomedical
Sponsor class: INDUSTRY
First posted: 2008-01-02
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 72 hours, 6 months
Secondary outcomes:
measure: To compare the diagnostic performance of PB127 MPE to SPECT for the detection and/or exclusion of significant obstructive coronary artery disease.
timeFrame: 72 hours, 6 months
measure: To assess the concordance of PB127 MPE with SPECT in the differentiation of defect type (fixed versus reversible) in patients with significant obstructive CAD.
timeFrame: 72 hours, 6 months
measure: To evaluate the diagnostic performance characteristics of PB127 MPE for identifying the location of significant obstructive CAD as defined by quantitative coronary angiography
timeFrame: 72 hours
measure: To assess the change in diagnostic certainty when PB127 MPE and relevant clinical information are combined over relevant clinical information alone.
timeFrame: 72 hours, 6 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Saver Heart Clinic
state: Arizona
city: Burlingame
country: United States
facility: Cardiovascular Associates of the Peninsula
state: California
city: Long Beach
country: United States
facility: Long Beach VA Medical Center Cardiology Division
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center Division of Cardiology
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego Division of Cardiology
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center NCIRE
state: California
city: Bridgeport
country: United States
facility: Connecticut Clinical Research
state: Connecticut
city: Newark
country: United States
facility: Alfieri Cardiology
state: Delaware
city: Washington
country: United States
facility: Washington Hospital Center Cardiovascular Research Institute
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Overland Park
country: United States
facility: Midwest Cardiology Associates
state: Kansas
city: Shawnee Mission
country: United States
facility: The Center for Cardiovascular Studies Kramer & Crouse Cardiology
state: Kansas
city: Paducah
country: United States
facility: Western Baptist Hospital The Heart Group
state: Kentucky
city: Auburn
country: United States
facility: Androscoggin Cardiovascular Associates
state: Maine
city: South Portland
country: United States
facility: Maine Cardiology Associates
state: Maine
city: Boston
country: United States
facility: Brigham & Women's Hosptial
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Department of Cardiology
state: Minnesota
city: Kansas City
country: United States
facility: Cardiovascular Consultants
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University Medical Center
state: Missouri
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: St. Luke's Roosevelt Hospital Echocardiography Lab
state: New York
city: Stonybrook
country: United States
facility: Stonybrook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: High Point
country: United States
facility: Carolina Cardiology Associates
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation Department of Cardiology
state: Ohio
city: Columbus
country: United States
facility: Ohio State University College of Medicine and Public Health
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center VA Medical Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cardiovascular Institute
state: Pennsylvania
city: Austin
country: United States
facility: Seton Healthcare Network Brackenridge Hospital
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Fort Worth
country: United States
facility: Consultants in Cardiology
state: Texas
city: Galveston
country: United States
facility: University of Texas Division of Cardiology
state: Texas
city: Houston
country: United States
facility: Methodist DeBakery Heart Center Cardiovascular Imaging Institute
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center Memorial Hermann Heart & Vascular Institute
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center Department of Cardiology
state: Washington
city: Spokane
country: United States
facility: Heart Clinics Northwest
state: Washington
city: Spokane
country: United States
facility: Inland Cardiology
state: Washington
city: Spokane
country: United States
facility: Northwest Cardiovascular Research Institute Spokane Cardiology
state: Washington
Study officials:
affiliation: POINT Biomedical Corp
name: Alexander Ehlgen, MD, PhD
role: STUDY_DIRECTOR
References: