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Heart Rate Reduction in Heart Failure

Effect of Ivabradine, Carvedilol or Their Combination in Patients With Heart Failure

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01178528
Acronym
CARVIVA-HF
Enrollment
121
Registered
2010-08-10
Start date
2009-09-30
Completion date
2010-10-31
Last updated
2014-09-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Keywords

heart failure, heart rate, ivabradine, carvedilol

Brief summary

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.

Detailed description

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

Interventions

DRUGivabradine

7.5 mg bd

DRUGDrug:Carvedilol and Drug:Ivabradine

up to 12.5/5 mg bd

DRUGCarvedilol

25 mg bd

Sponsors

IRCCS San Raffaele
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* heart failure II-III * ischemic origin * stable medications from at least 3 months * \> 3 months from an acute ischemic syndrome or revascularization procedure * naive on heart rate reducing agents

Exclusion criteria

* bradycardia * hypersensitivity or contraindications to study drugs * exercise tolerance at 6 minute walking test \<100 m or \>400 m

Design outcomes

Primary

MeasureTime frameDescription
Exercise Tolerance Assessed by 6 Minute Walking Test3 monthsDistance 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.
Maximal Oxygen Consumption3 monthsFunctional 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.

Secondary

MeasureTime frameDescription
Quality of Life3 monthsQuality 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.
New York Heart Association (NYHA) Class3 monthsThe 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.

Countries

Italy

Participant flow

Participants by arm

ArmCount
Ivabradine
up to 7.5 mg b.i.d.
41
Carvedilol
up to 25 mg b.i.d.
38
Carvedilol and Ivabradine
up to 12.5 / 5 mg b.i.d.
42
Total121

Baseline characteristics

CharacteristicIvabradineCarvedilolCarvedilol and IvabradineTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
11 Participants9 Participants10 Participants30 Participants
Age, Categorical
Between 18 and 65 years
30 Participants29 Participants32 Participants91 Participants
Exercise Tolerance Assessed by 6 Minute Walking Test346.7 meters
STANDARD_DEVIATION 112
379.0 meters
STANDARD_DEVIATION 96.3
358.2 meters
STANDARD_DEVIATION 107.6
361.3 meters
STANDARD_DEVIATION 105.3
Maximal Oxygen Consumption12.05 mL/Kg/min
STANDARD_DEVIATION 2.1
12.3 mL/Kg/min
STANDARD_DEVIATION 2.6
12.4 mL/Kg/min
STANDARD_DEVIATION 2.5
12.25 mL/Kg/min
STANDARD_DEVIATION 2.4
New York Heart Association (NYHA) class
class II
20 participants22 participants21 participants63 participants
New York Heart Association (NYHA) class
class III
21 participants16 participants21 participants58 participants
Quality of Life4.3 units on a scale
STANDARD_DEVIATION 0.5
4.6 units on a scale
STANDARD_DEVIATION 0.8
4.7 units on a scale
STANDARD_DEVIATION 0.8
4.5 units on a scale
STANDARD_DEVIATION 0.7
Region of Enrollment
Italy
41 participants38 participants42 participants121 participants
Sex/Gender, Customized
FEMALE
13 participants12 participants14 participants39 participants
Sex/Gender, Customized
MALE
28 participants26 participants28 participants82 participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 410 / 380 / 42
serious
Total, serious adverse events
0 / 410 / 380 / 42

Outcome results

Primary

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

ArmMeasureValue (MEAN)Dispersion
IvabradineExercise Tolerance Assessed by 6 Minute Walking Test474.8 metersStandard Deviation 127.3
CarvedilolExercise Tolerance Assessed by 6 Minute Walking Test435.7 metersStandard Deviation 121.3
Carvedilol and IvabradineExercise Tolerance Assessed by 6 Minute Walking Test453.1 metersStandard Deviation 87.4
Primary

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

ArmMeasureValue (MEAN)Dispersion
IvabradineMaximal Oxygen Consumption15.8 mL/Kg/minStandard Deviation 1.9
CarvedilolMaximal Oxygen Consumption12.9 mL/Kg/minStandard Deviation 2.4
Carvedilol and IvabradineMaximal Oxygen Consumption14.7 mL/Kg/minStandard Deviation 1.6
Secondary

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

ArmMeasureValue (NUMBER)
IvabradineNew York Heart Association (NYHA) Class30 participants
CarvedilolNew York Heart Association (NYHA) Class5 participants
Carvedilol and IvabradineNew York Heart Association (NYHA) Class20 participants
Secondary

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

ArmMeasureValue (MEAN)Dispersion
IvabradineQuality of Life6.7 units on a scaleStandard Deviation 0.9
CarvedilolQuality of Life4.1 units on a scaleStandard Deviation 0.6
Carvedilol and IvabradineQuality of Life6.1 units on a scaleStandard Deviation 0.6

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026