Evaluation of the anti-anginal efficacy and safetv of oral administration of Ivabradine compared fo placebo on top of abackground therapy with a calcium antagonist (amlodipine or Qifedipioe) in patients with stable angina pectoris. A 6 week randomised double-blind parallel-group Internationai multicentre study.
- Conditions
- -I209 Angina pectoris, unspecifiedAngina pectoris, unspecifiedI209
- Registration Number
- PER-087-07
- Lead Sponsor
- Institut de Recherches Internationales Servier I.R.I.S.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 60
• Man or woman who potentially can not have children (for an effective contraceptive method, sterilization, hysterectomy or menopause for more than 2 years). If required by local regulations or authorities for clinical studies, a pregnancy test will be carried out before administering any drug.
• Outpatients,> 18 years of age (or of legal age if legal age is reached later).
• History of stable chronic exertion angina for a minimum of 3 months before the selection.
• Stable angina is defined as angina pain from more than 3 months duration without angina at rest or a pattern of accelerated chest pain.
• Stress angina is defined as an anginal pain, typical or atypical, associated with physical activity, which lasts several minutes and disappears when physical activity is interrupted and / or fast-acting nitrates are ingested.
• Clinical stability: No significant change is observed in the frequency or severity of anginal attacks or triggering factors within a month before selection, nor in the consumption of nitrates. Clinical stability will be determined by asking the patient directly.
• Severity: No angina at rest or type IV angina is observed according to the classification of the Canadian Cardiovascular Society (see Appendix 7).
• Patients with at least 3 anginal attacks per week for a minimum of 2 weeks before selection (average value).
• Patients with a normal sinus rhythm.
• Patients who have received, for a minimum of 4 weeks before the screening visit, 5 mg of amiodipine once a day or 30 mg of nifedipine GITS once a day (or an equivalent dose of nifedipine prolonged release, ie , 20 mg twice a day).
• Patients who receive NAP may be selected if such treatment began at least 2 weeks before the selection. The NAP dose of these patients should remain stable throughout the entire study.
• Coronary artery disease (CAD) documented.
• The CAD will be documented in one of the following ways: - Antecedents of myocardial infarction> 3 months before the selection. The diagnosis will be confirmed by the Q waves of the ECG and / or a laboratory results sheet showing a significant increase in the concentration of cardiac enzymes.
• Percutaneous coronary intervention (PCI) (> 6 months before the selection).
• A coronary bypass surgery (CABG) (> 3 months before the selection).
• Coronary angiography (coronary angiography can be accepted by computed tomography) that shows significant stenosis (stenosis of> 50% in the proximal two thirds of at least one of the main coronary arteries, except the main left coronary artery); Stenosis is defined as a relative decrease in diameter. In the case of men who do not have documentation for the disease, who have positive PE and symptomatic angina, coronary angiography can be scheduled after the patient is included in the study.
• A positive scintigraphy that shows a reversible effort-induced ischemia (transient perfusion defect). If an isotope other than the stem is used, the researcher must register it in the CRF. In the case of men who do not have documentation for the disease, who have positive PE and symptomatic angina, scintigraphy may be scheduled after the patient is included in the study.
• Positive stress echocardiography (exercise-induced echocardiography or pharmacological stress) that shows motor wall abnormalities with failure in the normal increase in ejection fraction of the left ventricle with stress.
• An ST segment th
• It is unlikely that they will collaborate with the study.
• Pregnant women, who are breastfeeding or of childbearing age, who do not use intrauterine or progestogen contraceptive methods, or a combination of estrogen and progestogens, or women who do use intrauterine or progestogen contraceptive methods, or a combination of estrogen and progestin, but who they plan to stop doing it during the study period.
• Participation in another study simultaneously or during the month prior to entering the present study, or patients already enrolled in this study, except that they could not be included due to a negative PE before the approval and implementation of amendment 3 .
• Recently, acute myocardial infarction (less than 3 months before the selection), coronary bypass (less than 3 months before the selection) or PCI (less than 6 months before the selection).
• Angina at rest, unstable angina, Prinzmetal´s angina or microvascular angina.
• Disease of the left main coronary artery, known and high grade (equal to or greater than 50%), that has not undergone revascularization or that has not been mechanically improved.
• Patients with a pacemaker or implanted cardioverter defibrillator (ICD).
• Patients for whom a CABG or ICP has been scheduled during the course of the study.
• Cardiogenic shock.
• Relating to PE: Patients who interrupted the PE prior to inclusion before reaching the positivity criteria.
• Patients who can not undergo stress tests:
• Due to physical impossibility related to a neurological, orthopedic or rheumatological limiting disease, or to a symptomatic peripheral vascular disease of the lower extremities.
• Because it is contraindicated (eg, due to severe disturbances of rhythm or conduction, or thrombi in the left ventricle).
• Patients with abnormalities in the ECG that may lead to a misinterpretation of PE: Wolff-Parkinson-White syndrome, left ventricular hypertrophy (according to the Sokoloff index:> 45 mm with a higher S-wave measurement in the derivation VI or V2, and in the highest R wave in the V5 or V6 derivation), a complete block of the left branch, or known hyperventilation repolarization abnormalities.
• Flutter, permanent atrial fibrillation or paroxysmal atrial fibrillation at the time of selection.
• Clinically significant heart disease other than coronary artery disease (eg, congenital, hypertensive, pericardial, valvular, rheumatic, or nonischemic cardiomyopathy).
• Aneurysm of the abdominal aorta> 5 cm, aneurysm of the left ventricle.
• Congestive heart failure grade III or IV according to the NYHA classification (see Appendix 8) or uncontrolled heart failure.
• Symptomatic hypotension or BP <90/50 mm Hg.
• Uncontrolled hypertension (resting systolic blood pressure> 180 mm Hg or resting diastolic blood pressure> 100 mm Hg).
• FC <60 Ipm measured with a resting ECG during the selection.
• Any treatment with unauthorized concomitant medications (see section 10.3) that can not be interrupted during the entire course of the study.
• Treatment with amiodarone within 3 months prior to selection.
• Contraindication to ivabradine:
• 3 degree atrioventricular block
• Sick node syndrome
• Sinoauricular block
• Known hypersensitivity to ivabradine
• Contraindication to nifedipine GITS or amlodipine:
• Known hypersensitivity to nifedipine or amlodipine
• Severe gastrointestinal stricture
•
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Evaluated during a treatment period of 6 weeks, defined as a decrease of at least 3 anginal attacks per week and / or an increase in the time that elapses until a depression of 1 mm of the ST segment of a minimum of 60s occurs. a stress test (PE) on an endless tape<br>Measure:Response to treatmente<br>Timepoints:6 weeks<br>
- Secondary Outcome Measures
Name Time Method