Clinical trial NCT02236247: Control of Sinus Node Tachycardia as an Additional Therapy in Patients With Decompensated Heart Failure
Official title: Heart Rate Control as an Additional Therapeutic Strategy in Patients With Decompensated Heart Failure: a Prospective, Randomized, Double-blinded, Placebo-controlled Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Decompensated Heart Failure
Keywords: ivabradine
heart rate
heart failure
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2014-09-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline heart rate
timeFrame: Baseline, day 5 after intervention
Secondary outcomes:
measure: Change from baseline blood pressure
timeFrame: Baseline, day 5 after intervention
measure: Change from baseline ejection fraction
timeFrame: Baseline, day 5 after intervention
measure: Change from baseline stroke volume
timeFrame: Baseline, day 5 after intervention
measure: Change from baseline creatinine
timeFrame: Baseline, day 5 after intervention
measure: Change from baseline brain natriuretic peptide
timeFrame: Baseline, day 5 after intervention
measure: Clinical
timeFrame: Up to 6 months
Other outcomes:
measure: Safety/Adverse Event Outcome Measure
timeFrame: Up to day 15 days after intervention
Locations:
city: Sao Paulo
country: Brazil
facility: Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School
Study officials:
affiliation: Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School
name: Edimar A Bocchi, MD-PHD
role: STUDY_CHAIR
References:
citation: Lofrano-Alves MS, Issa VS, Biselli B, Chizzola P, Ayub-Ferreira SM, Bocchi EA. Control of sinus tachycardia as an additional therapy in patients with decompensated heart failure (CONSTATHE-DHF): A randomized, double-blind, placebo-controlled trial. J Heart Lung Transplant. 2016 Oct;35(10):1260-1264. doi: 10.1016/j.healun.2016.06.005. Epub 2016 Jun 7. No abstract available.