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Heart Rate Reduction in Heart Failure (CARVIVA-HF)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Giuseppe M.C. Rosano, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01178528
First received: April 19, 2010
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Drug: ivabradine
Drug: "Drug:Carvedilol" and "Drug:Ivabradine"
Drug: Carvedilol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Ivabradine, Carvedilol or Their Combination in Patients With Heart Failure

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • Exercise Tolerance Assessed by 6 Minute Walking Test [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    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.


  • Maximal Oxygen Consumption [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Quality of Life [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.

  • New York Heart Association (NYHA) Class [ Time Frame: 3 months ] [ Designated as safety issue: No ]

    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.



Enrollment: 121
Study Start Date: September 2009
Study Completion Date: October 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ivabradine
7.5 mg bd
Drug: ivabradine
7.5 mg bd
Active Comparator: Carvedilol
up to 25 mg bd
Drug: Carvedilol
25 mg bd
Experimental: "Drug:Carvedilol" and "Drug:Ivabradine"
up to 12.5/5 mg bd
Drug: "Drug:Carvedilol" and "Drug:Ivabradine"
up to 12.5/5 mg bd

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

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178528

Locations
Italy
Centre for Clinical and Basic Research - IRCCS San Raffaele
Roma, Italy, 00100
IRCCS San Raffaele
Roma, Italy, 00100
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Principal Investigator: Maurizio Volterrani, MD IRCCS San Raffaele
Study Chair: Giuseppe MC Rosano, MD, PhD IRCCS San Raffaele
Study Director: Cristiana Vitale, MD, PhD IRCCS San Raffaele
  More Information

Additional Information:
Publications:
Responsible Party: Giuseppe M.C. Rosano, Principal investigato, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT01178528     History of Changes
Other Study ID Numbers: CTG001-07
Study First Received: April 19, 2010
Results First Received: September 19, 2013
Last Updated: September 29, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by IRCCS San Raffaele:
heart failure
heart rate
ivabradine
carvedilol

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Carvedilol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 27, 2014