A Phase 3 interventional study of ivabradine and "Drug:Carvedilol" and "Drug:Ivabradine" in Heart Failure, sponsored by IRCCS San Raffaele. Completed at 2 sites in Italy. Open to participants aged 35 Years and older. Per ClinicalTrials.gov, last updated 2014-09-30.
Sponsored by IRCCS San Raffaele · Phase 3, Interventional, and Treatment
Patients with heart failure (HF) have a limited exercise tolerance,few pharmacological interventions have been proven effective in improving exercise capacity. At the presence there i conflicting evidence on the effectiveness of beta-blockers on exercise capacity. Ivabradine has been shown to improve prognosis in patients with ischemic heart disease, left ventricular dysfunction and heart rate > 70 bpm. The association of ivabradine and atenolol has been proven effective in increasing exercise tolerance in patients with ischemic heart disease. Aim of the present study is to evaluate the effect of heart rate reduction with ivabradine, carvedilol or their combination in patients with heart failure of ischemic origin.
Patients with chronic heart failure of ischemic origin (120) Stable coronary artery disease Acute coronary syndromes > 3 months Revascularization procedures > 3 months Naive on heart rate reducing agents New York Heart Association (NYHA) Class II III 6 minute walking test (6MW) tolerance between 200 and 400 m Stable medications for the past 3 months
Treatment Ivabradine up to 7.5 mg b.i.d. Carvedilol up to 25 mg b.i.d. Carvedilol and Ivabradine up to 12.5/5 mg b.i.d.
Efficacy measure Intention to treat Exercise tolerance Quality of life
5,803 studies on the registry are indexed under Heart Failure; 1,222 are open to participants now.
This study's enrollment of 121 is above the median of 72 across 3,790 interventional studies indexed under Heart Failure.
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Exclusion Criteria:
7.5 mg bd
Drug: ivabradine
up to 25 mg bd
Drug: Carvedilol
up to 12.5/5 mg bd
Drug: "Drug:Carvedilol" and "Drug:Ivabradine"
7.5 mg bd
up to 12.5/5 mg bd
25 mg bd
Exercise Tolerance Assessed by 6 Minute Walking Test
Distance measured at 6 minute walking test. The 6 minute walking test was performed according to standardised procedure at baseline, before inclusion (at least 1 week after baseline evaluation), and at the end of the study. Patients who had not done at least two tests in the past underwent two practice 6 minute walking tests at least 3 days apart. Results are expressed in terms of distance walked (metres). The test was supervised by a physical therapist. Patients were asked to walk at their own maximal pace a 100 m long hospital corridor. At the beginning of the last (6th) minute of the test a standard phrase of encouragement was told. Patients were allowed to stop if signs or symptoms of significant distress occurred (dyspnea, angina), through they were instructed to resume walking as soon as possible.
Time frame: 3 months
Maximal Oxygen Consumption
Functional capacity was assessed by means of a cardiopulmonary exercise test with a bicycle ergometer with gas exchange monitoring (Vmax 29 C, SensorMedics). Peak oxygen consumption was defined as the maximal oxygen consumption (MVO2) observed during exercise.
Time frame: 3 months
Quality of Life
Quality of life (QoL) was evaluated using the Visual Analogue Scale (VAS) which is a global measurement of QoL, allowing a subjective assessment of the impact of the disease and treatment. Patients are asked to indicate their current state in a line from 0 (worst state) to 10 (best state), with higher values therefore representing a better outcome.
Time frame: 3 months
New York Heart Association (NYHA) Class
The 1994 NYHA Classification system is a measure of functional status. It was designed for clinical assessment of patients by physicians as NYHA class I, II, III, or IV, on the basis of patient's limitations in physical activities caused by cardiac symptoms. Class I describes patients with cardiovascular disease (CVD) but without resulting limitation of physical activity. There is no objective evidence of CVD. Class II describes patients with CVD resulting in slight limitation of physical activity. There is objective evidence of minimal CVD. Class III describes patients with CVD resulting in marked limitation of physical activity. There is objective evidence of moderately severe CVD. Class IV describes patients with CVD resulting in inability to carry on any physical activity without discomfort. There is objective evidence of severe CVD. Here we report data on number of patients showing an improvement by at least one NYHA class according to treatment allocation.
Time frame: 3 months
| Milestone | Ivabradine | Carvedilol | Carvedilol and Ivabradine |
|---|---|---|---|
| Started | 41 | 38 | 42 |
| Completed | 41 | 38 | 42 |
| Not completed | 0 | 0 | 0 |
Distance measured at 6 minute walking test. The 6 minute walking test was performed according to standardised procedure at baseline, before inclusion (at least 1 week after baseline evaluation), and at the end of the study. Patients who had not done at least two tests in the past underwent two practice 6 minute walking tests at least 3 days apart. Results are expressed in terms of distance walked (metres). The test was supervised by a physical therapist. Patients were asked to walk at their own maximal pace a 100 m long hospital corridor. At the beginning of the last (6th) minute of the test a standard phrase of encouragement was told. Patients were allowed to stop if signs or symptoms of significant distress occurred (dyspnea, angina), through they were instructed to resume walking as soon as possible.
| meters | Ivabradine | Carvedilol | Carvedilol and Ivabradine |
|---|---|---|---|
| Exercise Tolerance Assessed by 6 Minute Walking Test | 474.8 ± 127.3 | 435.7 ± 121.3 | 453.1 ± 87.4 |
Quality of life (QoL) was evaluated using the Visual Analogue Scale (VAS) which is a global measurement of QoL, allowing a subjective assessment of the impact of the disease and treatment. Patients are asked to indicate their current state in a line from 0 (worst state) to 10 (best state), with higher values therefore representing a better outcome.
| units on a scale | Ivabradine | Carvedilol | Carvedilol and Ivabradine |
|---|---|---|---|
| Quality of Life | 6.7 ± 0.9 | 4.1 ± 0.6 | 6.1 ± 0.6 |
Functional capacity was assessed by means of a cardiopulmonary exercise test with a bicycle ergometer with gas exchange monitoring (Vmax 29 C, SensorMedics). Peak oxygen consumption was defined as the maximal oxygen consumption (MVO2) observed during exercise.
| mL/Kg/min | Ivabradine | Carvedilol | Carvedilol and Ivabradine |
|---|---|---|---|
| Maximal Oxygen Consumption | 15.8 ± 1.9 | 12.9 ± 2.4 | 14.7 ± 1.6 |
The 1994 NYHA Classification system is a measure of functional status. It was designed for clinical assessment of patients by physicians as NYHA class I, II, III, or IV, on the basis of patient's limitations in physical activities caused by cardiac symptoms. Class I describes patients with cardiovascular disease (CVD) but without resulting limitation of physical activity. There is no objective evidence of CVD. Class II describes patients with CVD resulting in slight limitation of physical activity. There is objective evidence of minimal CVD. Class III describes patients with CVD resulting in marked limitation of physical activity. There is objective evidence of moderately severe CVD. Class IV describes patients with CVD resulting in inability to carry on any physical activity without discomfort. There is objective evidence of severe CVD. Here we report data on number of patients showing an improvement by at least one NYHA class according to treatment allocation.
| participants | Ivabradine | Carvedilol | Carvedilol and Ivabradine |
|---|---|---|---|
| New York Heart Association (NYHA) Class | 30 | 5 | 20 |
Collected over 3 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ivabradine | — | 0/41 (0%) | 0/41 (0%) |
| Carvedilol | — | 0/38 (0%) | 0/38 (0%) |
| Carvedilol and Ivabradine | — | 0/42 (0%) | 0/42 (0%) |
| Age, Categorical(Participants) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 30 | 29 | 32 | 91 |
| >=65 years | 11 | 9 | 10 | 30 |
| Sex/Gender, Customized(participants) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| MALE | 28 | 26 | 28 | 82 |
| FEMALE | 13 | 12 | 14 | 39 |
| Region of Enrollment(participants) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| Italy | 41 | 38 | 42 | 121 |
| Exercise Tolerance Assessed by 6 Minute Walking Test(meters) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| Mean | 346.7 ± 112.0 | 379.0 ± 96.3 | 358.2 ± 107.6 | 361.3 ± 105.3 |
| Maximal Oxygen Consumption(mL/Kg/min) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| Mean | 12.05 ± 2.1 | 12.3 ± 2.6 | 12.4 ± 2.5 | 12.25 ± 2.4 |
| Quality of Life(units on a scale) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| Mean | 4.3 ± 0.5 | 4.6 ± 0.8 | 4.7 ± 0.8 | 4.5 ± 0.7 |
| New York Heart Association (NYHA) class(participants) | Ivabradine | Carvedilol | Carvedilol and Ivabradine | Total |
|---|---|---|---|---|
| class II | 20 | 22 | 21 | 63 |
| class III | 21 | 16 | 21 | 58 |
The record gives a start of Sep 2009, a primary completion of Jun 2010 and a completion of Oct 2010. It does not say whether these dates are actual or estimated.
Results were first posted in Sep 2014, 4 years 3 months after primary completion.
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Studies of the drug tested here: Ivabradine