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

Decompensated Heart Failure Clinical Trial

— CONSTATHE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02236247
• Other study ID #: CAAE:09145612.8.0000.0068
• Secondary ID: 2012/06163-6
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 2, 2014
• Last updated: December 30, 2016
• Start date: May 2013
• Est. completion date: August 2017

Study information

• Verified date: December 2016
• Source: University of Sao Paulo
• Contact: Marco S. Alves, MD
• Phone: +55 11 981431512
• Email: marco.alves[@]incor.usp.br
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• ivabradine
5 mg oral twice daily
• Placebo
A placebo pill (identical to ivabradine) will be administered twice daily

Locations

Country	Name	City	State
Brazil	Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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 Hear — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety/Adverse Event Outcome Measure	Number of Participants with Serious and Non-Serious Adverse Events	Up to day 15 days after intervention	Yes
Primary	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	Yes
Secondary	Change from baseline blood pressure	Blood pressure will be measured at morning by electronic cuff	Baseline, day 5 after intervention	Yes
Secondary	Change from baseline ejection fraction	Ejection fraction will be measured by echocardiography using Simpson´s rule	Baseline, day 5 after intervention	No
Secondary	Change from baseline stroke volume	Stroke volume will be measured by echocardiography using Doppler velocity-time integral technique.	Baseline, day 5 after intervention	Yes
Secondary	Change from baseline creatinine	Serum creatinine will be measured	Baseline, day 5 after intervention	Yes
Secondary	Change from baseline brain natriuretic peptide	Serum brain natriuretic peptide will be measured	Baseline, day 5 after intervention	No
Secondary	Clinical	Time of survival and free of readmission	Up to 6 months	No

External Links

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