Decompensated Heart Failure
Conditions
Keywords
ivabradine, heart rate, heart failure
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.
Interventions
DRUGivabradine
5 mg oral twice daily
DRUGPlacebo
A placebo pill (identical to ivabradine) will be administered twice daily
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline heart rate | Baseline, day 5 after intervention | Heart rate will be assessed at morning, after 30 minutes of rest, recorded by electrocardiogram. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline blood pressure | Baseline, day 5 after intervention | Blood pressure will be measured at morning by electronic cuff |
| Change from baseline ejection fraction | Baseline, day 5 after intervention | Ejection fraction will be measured by echocardiography using Simpson´s rule |
| Change from baseline stroke volume | Baseline, day 5 after intervention | Stroke volume will be measured by echocardiography using Doppler velocity-time integral technique. |
| Change from baseline brain natriuretic peptide | Baseline, day 5 after intervention | Serum brain natriuretic peptide will be measured |
| Clinical | Up to 6 months | Time of survival and free of readmission |
| Change from baseline creatinine | Baseline, day 5 after intervention | Serum creatinine will be measured |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety/Adverse Event Outcome Measure | Up to day 15 days after intervention | Number of Participants with Serious and Non-Serious Adverse Events |
Countries
Brazil
Contacts
Primary ContactMarco S. Alves, MD
Backup ContactEdimar A. Bocchi, MD-PHD
Outcome results
None listed