Phase II Study for the Diagnosis and Functional Assessment of CAD Using Transthoracic-Echodoppler

Ischemic Heart Disease Clinical Trial

Official title:

Phase 2, Monocentric, Single Blind Study, Comparing the Efficacy and Tolerance of a Dipyridamole/Adenosine Combination Given Intravenously, as a Slow Bolus and at Low Doses to Adenosine Alone for Coronary Flow Reserve Assessment (in Patients With Stable Ischemic Heart Disease) Using Transthoracic Echodoppler

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01593644
• Other study ID #: ADEN-Ph2-2011-1
• Status: Recruiting
• Phase: Phase 2
• First received: May 6, 2012
• Last updated: September 6, 2012
• Start date: June 2011

Study information

• Verified date: September 2012
• Source: Adenobio N.V
• Contact: Philippe GORNY, PhD,MD
• Phone: +33 616 764 464
• Email: pg[@]adenobio.com
• Is FDA regulated: No
• Health authority: France:ANSM formely called Afssaps - French Health Products Safety Agency
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Diseases
• Ischemic Heart Disease
• Myocardial Ischemia

Intervention

Drug:
• adenosine + dipyridamole
adenosine / dipyridamole combination given intravenously as a slow bolus at low doses

Locations

Country	Name	City	State
France	Centre Hospitalier de Compiègne	Compiègne

Sponsors (1)

Lead Sponsor	Collaborator
Adenobio N.V

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diastolic mean and peak coronary blood velocities	hemodynamic efficacy, with maintenance of the optimal hyperemic coronary effect for at least 45 to 60 seconds after the end of the injection	2 minutes	No
Secondary	Incidence rate and severity of adverse events, in particular, chest pain, dyspnoea, hypotension, bradycardia, AV blocks, arrhythmia.	Incidence rate of A1 adverse events and of the severity of A2 and A1 clinical symptoms	24 hours	No