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

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

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

Study Overview

• Status: Unknown
• Conditions: Decompensated Heart Failure
• Intervention / Treatment: Drug: ivabradine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-900
    • Recruiting
    • Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School
    • Contact: Marco S Alves, MD; Phone Number: +55 11 981431512; Email: marco.alves@incor.usp.br
    • Contact: Edimar A Bocchi, MD-PHD; Phone Number: +55 11 2661-5419; Email: edimar.bocchi@incor.usp.br
    • Principal Investigator: Marco S Alves, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/Adverse Event Outcome Measure	Number of Participants with Serious and Non-Serious Adverse Events	Up to day 15 days after intervention

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Study Chair: Edimar A Bocchi, MD-PHD, Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): August 1, 2017

Study Registration Dates

• First Submitted: September 2, 2014
• First Submitted That Met QC Criteria: September 9, 2014
• First Posted (Estimate): September 10, 2014

Study Record Updates

• Last Update Posted (Estimate): January 2, 2017
• Last Update Submitted That Met QC Criteria: December 30, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: heart failure; ivabradine; heart rate
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CAAE:09145612.8.0000.0068; 2012/06163-6 (Other Grant/Funding Number: FAPESP - SAO PAULO RESEARCH FOUNDATION)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO