Efficacy Study of Digoxin & Ivabradine to Treat Heart Failure

Phase 4

Completed

• Conditions: Cardiac Failure
• Interventions: Drug: Ivabradine; Drug: Digoxin

• Registration Number: NCT01699776
• Lead Sponsor: Cocco, Giuseppe, M.D.

Brief Summary

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).

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.

Study Timeline

• Study Start: 2008-04
• Primary Completion: 2012-02
• Study Completion: 2012-02
• Study First Submitted: 2012-09-12
• Status Verified: 2012-10
• Study First Submitted QC: 2012-10-03
• Study First Posted: 2012-10-04
• Last Update Submitted: 2013-11-08
• Last Update Posted: 2013-11-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ivabradine	Ivabradine	Ivabradine, 7,5 mg b.id. by mouth for 14-16 weeks.
Digoxin	Digoxin	Digoxin 0.125 mg once a day, 5 times per week, for 12-14 weeks by mouth.

Primary Outcome Measures

Name	Time	Method
Comparative therapeutic effect.	6 months	Effects on symptoms and signs of cardiac failure.

Trial Locations

Locations (1)

Cardiology office; 🇨🇭 Rheinfelden, Argovia, Switzerland