Control of Sinus Node Tachycardia as an Additional Therapy in Patients With Decompensated Heart Failure

Study Overview
=================
Brief Summary
-----------------
Study aims to compare the I(f) inhibitor ivabradine with placebo as strategy of heart rate control in patients with decompensated heart failure (DHF).

Detailed Description
-----------------
Sympathetic hyperactivity and consequent increase in heart rate (HR) are physiological responses to low cardiac output in patients with decompensated heart failure (DHF). However, elevated HR may become inappropriate in these patients, increasing myocardial oxygen demand and decreasing diastolic filling time and might lead to hemodynamic deterioration, ventricular dysfunction (tachycardiomyopathy) and clinical deterioration. Studies show the elevated HR is a predictor of poor prognosis in DHF. Subanalyses of large clinical trials using beta blockers (BBs) demonstrate the adequate control of HR correlates with a better outcome in patients with stable chronic heart failure (HF). However, use of BBs in patients with DHF is limited due to negative inotropic and hypotensive effects of these drugs. As alternative to BBs, ivabradine has shown to increase survival of patients with chronic stable systolic HF. Compared to BBs, ivabradine has the advantage of pure negative chronotropic effect, no effect on myocardial contractility or peripheral vascular resistance. Despite the inhibition of I (f) has been validated as a therapeutic option in patients with stable HF, there are no studies available on this strategy in patients with DHF. We hypothesized that HR control by ivabradine might improve clinical, hemodynamic and neurohormonal parameters in patients with DHF. The aim of this study was to evaluate the efficacy of HR control with ivabradine in patients with DHF.

Official Title
-----------------
Heart Rate Control as an Additional Therapeutic Strategy in Patients With Decompensated Heart Failure: a Prospective, Randomized, Double-blinded, Placebo-controlled Study.

Conditions
-----------------
Decompensated Heart Failure

Intervention / Treatment
-----------------
* Drug: ivabradine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sinus node rhythm HR> 80 bpm Hospitalization for DHF Ejection fraction ≤ 40% Sign informed consent Exclusion Criteria: Systolic blood pressure <85 mmHg Signs of hypoperfusion Dobutamine>15 mcg/Kg/min Acute myocarditis Primary valvular disease requiring surgery Stroke in the last three months Hypertrophic or restrictive cardiomyopathy Sinus node disease Atrial fibrillation or flutter Second or third degree atrio-ventricular blockade Long QT syndrome Severe pulmonary disease Pulmonary embolism in the last three months Need for invasive ventilatory support Septicemia or septic shock Hepatic failure Creatinine > 2.5 mg/dL Hemodialysis Advanced malignancy Pregnancy or lactation Immunosuppressive therapy Use of cytochrome P450 inhibitors

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ivabradine<br>I(f) inhibitor, heart rate controller | Drug: ivabradine<br>* 5 mg oral twice daily<br>* Other names: procoralan;|
| Placebo Comparator: placebo<br>placebo pill will be administered orally twice daily | Drug: Placebo<br>* A placebo pill (identical to ivabradine) will be administered twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline heart rate | Heart rate will be assessed at morning, after 30 minutes of rest, recorded by electrocardiogram. | Baseline, day 5 after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline blood pressure | Blood pressure will be measured at morning by electronic cuff | Baseline, day 5 after intervention | 
| Change from baseline ejection fraction | Ejection fraction will be measured by echocardiography using Simpson´s rule | Baseline, day 5 after intervention | 
| Change from baseline stroke volume | Stroke volume will be measured by echocardiography using Doppler velocity-time integral technique. | Baseline, day 5 after intervention | 
| Change from baseline creatinine | Serum creatinine will be measured | Baseline, day 5 after intervention | 
| Change from baseline brain natriuretic peptide | Serum brain natriuretic peptide will be measured | Baseline, day 5 after intervention | 
| Clinical | Time of survival and free of readmission | Up to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ivabradine, heart rate, heart failure