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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00595244
• Other study ID #: 127-006
• Status: Completed
• Phase: Phase 3
• First received: January 7, 2008
• Last updated: July 1, 2008
• Start date: July 2002
• Est. completion date: October 2003

Study information

• Verified date: July 2008
• Source: Point Biomedical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 456
• Est. completion date: October 2003
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• PB127 for injectable suspension
0.175 mg/kg diluted in 150 mL Dextrose in Water 5% in glass bottles to be infused at 250 mL/hour until stead state achieve, 150 mL/hour during rest image acquisition, and 100-150 mL/hr during stress image acquistion. Single IV infusion, not to exceed 60 minutes.

Locations

Country	Name	City	State
United States	New England Medical Center	Boston	Massachusetts
United States	The Cleveland Clinic Foundation Department of Cardiology	Cleveland	Ohio
United States	Long Beach VA Medical Center Cardiology Division	Long Beach	California
United States	Michael Morgan, MD	Phoenix	Arizona
United States	University of Pittsburgh Cardiovascular Institute	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	University of Texas Health Sciences Center at San Antonio	San Antonio	Texas
United States	University of California San Diego Division of Cardiology	San Diego	California
United States	San Francisco VA Medical Center NCIRE	San Francisco	California
United States	Harborview Medical Center Department of Cardiology	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	The Center for Cardiovascular Studies Kramer & Crouse Cardiology	Shawnee Mission	Kansas
United States	Northwest Cardiovascular Research Institute Spokane Cardiology	Spokane	Washington
United States	St. Louis University Medical Center	St. Louis	Missouri
United States	Washington Hospital Center Cardiovascular Research Institute	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Point Biomedical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	To compare the diagnostic performance of PB127 MCE with stress SPECT in identifying the location of stenosis as identified by coronary angiography.		28 days	Yes