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

Phase 1
Conditions
Decompensated Heart Failure
Interventions
Drug: Placebo
Registration Number
NCT02236247
Lead Sponsor
University of Sao Paulo
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboPlaceboplacebo pill will be administered orally twice daily
ivabradineivabradineI(f) inhibitor, heart rate controller
Primary Outcome Measures
NameTimeMethod
Change from baseline heart rateBaseline, day 5 after intervention

Heart rate will be assessed at morning, after 30 minutes of rest, recorded by electrocardiogram.

Secondary Outcome Measures
NameTimeMethod
Change from baseline blood pressureBaseline, day 5 after intervention

Blood pressure will be measured at morning by electronic cuff

Change from baseline ejection fractionBaseline, day 5 after intervention

Ejection fraction will be measured by echocardiography using Simpson´s rule

Change from baseline stroke volumeBaseline, day 5 after intervention

Stroke volume will be measured by echocardiography using Doppler velocity-time integral technique.

Change from baseline creatinineBaseline, day 5 after intervention

Serum creatinine will be measured

Change from baseline brain natriuretic peptideBaseline, day 5 after intervention

Serum brain natriuretic peptide will be measured

ClinicalUp to 6 months

Time of survival and free of readmission

Trial Locations

Locations (1)

Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School

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Sao Paulo, Brazil

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