Efficacy Study of Digoxin & Ivabradine to Treat Heart Failure (Dig&Iva)

This study has been completed.
Sponsor:
Collaborator:
Cardiology Office Rheinfelden
Information provided by (Responsible Party):
Cocco G., M.D., Cocco, Giuseppe, M.D.
ClinicalTrials.gov Identifier:
NCT01699776
First received: September 12, 2012
Last updated: November 8, 2013
Last verified: October 2012
  Purpose

It is established that at a serum concentration 0.5-0.9 ng/ml digoxin is effective in patients with heart failure, especially in the presence of atrial fibrillation (AF). It is the claimed that ivabradine by lowering heart rate reduces symptoms and improves clinical outcomes in patients with heart failure. The effect of ivabradine and digoxin in heart failure was compared.

Patients 22 patients with ischemic heart failure, AF, and diastolic dysfunction with preserved left ventricular systolic function were treated with digoxin and ivabradine for 3 months, according to a randomization cross-over design.

Collected data Medical history, physical examination, laboratory (including proBNP and serum digoxin concentrations), ECG, 6-minute walk test, and echocardiographic data (LVEF, LAVi, e/e1 ratio).


Condition Intervention Phase
Cardiac Failure
Drug: Ivabradine
Drug: Digoxin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Comparison of Digoxin and Ivabradine in Heart Failure With Preserved Systolic Function. Time to Rethink About Digoxin.

Resource links provided by NLM:


Further study details as provided by Cocco, Giuseppe, M.D.:

Primary Outcome Measures:
  • Comparative therapeutic effect. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Effects on symptoms and signs of cardiac failure.


Enrollment: 22
Study Start Date: April 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ivabradine
Ivabradine, 7,5 mg b.id. by mouth for 14-16 weeks.
Drug: Ivabradine
7.5 my b.id. by mouth for 12-14 weeks
Other Name: Procoralan
Active Comparator: Digoxin
Digoxin 0.125 mg once a day, 5 times per week, for 12-14 weeks by mouth.
Drug: Digoxin
1.25 mg once a day by mouth, for 12-14 weeks.
Other Name: Digoxin

Detailed Description:

Protocol This is an investigator-started study, coded GC&PJ-dig-Iva 2009-2012. The study was planned according to the Good Clinical Quality standards and the analysis was performed using an intention-to-treat method. The protocol was approved from an Ethics Committee. Selected patients gave their written informed consent. The family practitioners agreed and obtained the data and analysis. Collected data were analyzed from single-blinded investigators (without knowledge of the used test drug and time of collection).

Patients Study design: same patients were assigned to DIG or IVA for 3 months, according to a randomization cross-over design.

Tested drugs Commercial brands of digoxin and ivabradine were used. Digoxin was given by mouth at a dose of 0.125 mg/day, 5 times per week, for 3 months.

Ivabradine was given by mouth at a dose of 7.5 mg bid for 3 months.

Inclusion criteria Chronic and stable coronary artery disease Permanent atrial fibrillation. Diastolic dysfunction with maintained systolic function.

Exclusion criteria Unstable angina pectoris. Reduced systolic cardiac function (LVEF<52%). Normal diastolic function. Diabetes requiring insulin. Moderate or severe renal or hepatic dysfunction. Technically insufficient echocardiographic quality.

Collected data Medical history and concomitant medications. Physical examination was performed. Laboratory values (including proBNP and serum digoxin concentration). ECG. Echocardiography. 6-minute walk test.

Statistical Analyses Data are expressed as mean ± 1 SD. Absolute values and percent changes in relation to baseline measurements were analyzed. The 2 hypotheses tested were: null hypothesis: mu1-mu2=0.0, and alternative hypothesis: mu1-mu2>>0.0. Comparisons within groups were made using paired t tests or the non-parametric Wilcoxon signed-rank test, where appropriate. Between-group comparisons were performed by unpaired t tests or the non-parametric Mann-Whitney U test, respectively. Chi-square test or Kruskal-Wallis test were used to compare continuous normally or not normally distributed and qualitative variables, where appropriate. Multivariate analysis of variance was performed. A p value of < 0.05 was considered statistically significant.

  Eligibility

Ages Eligible for Study:   60 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients had heart failure NYHA (New York Heart Association) class III. All had chronic and stable coronary artery disease which had been treated with percutaneous dilatation and stenting, and/or aortocoronary bypass. The pathology had induced a permanent AF and heart failure with left ventricular diastolic dysfunction and preserved systolic function. Preserved systolic function was defined by a LVEF (left ventricular ejection fraction) ≥52%. Left ventricular diastolic dysfunction was defined by a e/e1 ratio > 15 (septal spectral tissue-Doppler).

Exclusion Criteria:

Unstable myocardial ischemia, reduced systolic cardiac function (LVEF<52%), diabetes mellitus requiring insulin, moderate or severe renal or hepatic dysfunction, or technically insufficient echocardiography.

  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: NCT01699776

Locations
Switzerland
Cardiology office
Rheinfelden, Argovia, Switzerland, CH-4310
Sponsors and Collaborators
Cocco, Giuseppe, M.D.
Cardiology Office Rheinfelden
Investigators
Principal Investigator: Giuseppe Cocco, MD Cardiologist, senior lecturer
  More Information

No publications provided

Responsible Party: Cocco G., M.D., M.D., FESC, Cocco, Giuseppe, M.D.
ClinicalTrials.gov Identifier: NCT01699776     History of Changes
Other Study ID Numbers: CG&PJ-Dig-Iva 2009-2012
Study First Received: September 12, 2012
Last Updated: November 8, 2013
Health Authority: Switzerland: Laws and standards

Keywords provided by Cocco, Giuseppe, M.D.:
Digoxin
Ivabradine
with atrial fibrillation.

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Digoxin
Anti-Arrhythmia Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014