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

University of Sao Paulo

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Decompensated Heart Failure

Treatments: Drug: ivabradine; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02236247

CAAE:09145612.8.0000.0068

2012/06163-6 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

ivabradine

Experimental group

Description:

I(f) inhibitor, heart rate controller

Treatment:

Drug: ivabradine

placebo

Placebo Comparator group

Description:

placebo pill will be administered orally twice daily

Treatment:

Drug: Placebo