Phase II Study for the Diagnosis and Functional Assessment of CAD Using Transthoracic-Echodoppler
Phase II Study for the Diagnosis and Functional Assessment of CAD Using Transthoracic-Echodoppler
The purpose of this study is to evaluate the efficacy and tolerance of a
 dipyridamole/adenosine combination given intravenously, as a slow bolus and at low doses to
 adenosine alone (given at its recommended dosage adjusted to patients' weight) for coronary
 flow reserve assessment (in 60-75 patients with stable ischemic heart disease) using
 transthoracic echodoppler
Phase 2, monocentric, single blind study, comparing the efficacy (primary endpoint) and the
 safety-tolerance profile (secondary endpoint) of a dipyridamole/adenosine combination given
 intravenously as a slow bolus and at low doses to adenosine alone given by the same route at
 its standard and recommended dose.

 Expected results: Non inferiority of the combination compared to standard adenosine alone in
 terms of hemodynamic efficacy, with maintenance of the optimal hyperemic coronary effect for
 at least 45 to 60 seconds after the end of the injection -Significant reduction of the
 incidence rate of A1 adverse events and of the severity of A2 and A1 clinical symptoms.

 Primary endpoint : diastolic mean and peak coronary blood velocities Secondary endpoint :
 incidence rate and severity of adverse events, in particular, chest pain, dyspnoea,
 hypotension, bradycardia, AV blocks, arrhythmia

 Number of patients: 60-75 pts with 42-50 pts acceptable for statistical analysis

 Operating procedures:

 Day 1 (visit): Informed consent signature, Review of inclusion and exclusion criteria,
 Hemodynamic variables and EKG, Cardiac history, Significant other medical diseases, Risk
 factors, Concomitant treatment and substances consumed within 48 hours, Transthoracic
 ultrasonography, Adverse events report Day 2 (telephone contact): Adverse events report

 Duration of the study: 15 months

 Statistical Analysis: Statistical tests will include :a paired test analysis and comparison
 of the means (quantitative variables) -Possibly the Mac-Nemar test for the assessment of
 clinical adverse events during the study test with both products.
Inclusion Criteria:

 -  Man or post-menopausal woman or with an oral contraceptive treatment , > 18 years

 -  Provided written consent by patient with good understanding of the study objectives as
 explained by the investigator during the initial visit

 -  Patient with a potential or known Coronary Artery Disease

 -  Patient for whom transthoracic ultrasonography for coronary reserve assessment is
 deemed useful

 Exclusion Criteria:

 -  Subjects under 18, pregnant or breast-feeding woman, psychotic patients or subjects
 placed under administrative and legal authority

 -  Patients judged by investigator as not able to understand the study objectives

 -  Patients with a medical history, in particular a heart disease history (eg AV block)
 judged as non eligible by investigator

 -  Patients whose medical treatment contra- indicates their inclusion in the study (eg
 chronic use of oral dipyridamole, pentoxifylline), if not stopped at least 72 hours
 before the study test

 -  Patients with symptomatic bradycardia (<40 beat/min) or with systemic hypotension (SBP
 > 90 mmHg

 -  Patients with a 2nd and 3rd degree AV block, a sick sinus syndrome, but not those with
 artificial pacemaker

 -  Patients with prolonged QT (QTc>480 ms)

 -  Patients with oral dipyridamole who did not stopped their medication 48hrs before the
 study test

 -  Patients who received theophylline within 5 days before study test

 -  Consumption of coffee, cola, tea, chocolate within 12 hrs before study test

 -  Patients with a history of unstable Asthma or Chronic Obstructive Pulmonary Disease
 with bronchoconstriction

 -  Patients with unstable angina pectoris or uncontrolled severe heart failure

 -  Patients with a recent myocardial infarction history (<7 days), or stroke episode (< 1
 month)

 -  Patients with known TC stenosis and not yet revascularized, uncontrolled hypovolemia,
 known and unfixed valvular stenosis, left-right shunt, pericarditis, sympathetic
 nervous system dysfunction, carotid stenosis , any significant cerebrovascular
 insufficiency

 -  Patients with known allergy to adenosine or dipyridamole