Losartan in Decompensated Heart Failure

Short-term add-on Therapy With Angiotensin Receptor Blocker for End-stage Inotrope-dependent Heart Failure Patients: B-type Natriuretic Peptide Reduction in a Randomized Clinical Trial

The dual blockade of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor and an angiotensin-receptor blocker used together in heart failure patients has been demonstrated to be beneficial. However, the dual inhibition has not been studied during heart failure decompensation or even when low cardiac output is present.

The objective of this study was to assess the effects of add-on therapy with angiotensin receptor blocker on plasma B-type natriuretic peptide levels and hemodynamic measurements in heart failure patients with low cardiac output during hospitalization for decompensation.

This was a randomized, double-blind, placebo-controlled clinical trial.

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure; Low Cardiac Output
• Intervention / Treatment: Drug: Placebo; Drug: Losartan

Detailed Description

The inclusion criteria were hospitalization for decompensated heart failure defined by worsening of symptoms until fatigue or dyspnea at rest, low cardiac output defined by the clinical-hemodynamic profile, dobutamine dependence, and ejection fraction < 0.45, spontaneous breathing and receiving angiotensin-converting enzyme inhibitors. The patients could have jugular ingurgitation, lower limbs edema, ascites and rales. Dobutamine dependence was defined by infusion for more than 15 days or an unsuccessful attempt of withdrawal.

The exclusion criteria were serum creatinine > 3.0 mg/dL, serum potassium > 6.0 mEq/L, systolic blood pressure < 70 mm Hg, aortic stenosis, and acute coronary syndrome in the previous 2 months. The patients were randomly assigned by permuted block of 4, stratified by sex, to losartan or placebo.

The endpoints were change in B-type natriuretic peptide levels, cardiac index, pulmonary wedge capillary pressure, systemic vascular resistance, and successful withdrawal of dobutamine.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05021-010
      • Cotoxó Hospital, Heart Institute (InCor), University of São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• hospitalization for decompensated heart failure
• dobutamine dependence
• ejection fraction < 0.45
• taking angiotensin-converting enzyme inhibitor

Exclusion Criteria:

• serum creatinine > 3.0 mg/dL
• serum potassium > 6.0 mEq/L
• systolic blood pressure < 70 mm Hg
• aortic stenosis
• acute coronary syndrome in the previous 2 months

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: Losartan; Losartan 50 mg bid orally	Drug: Losartan
Placebo Comparator: Placebo; Placebo 1 pill bid orally	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B-type natriuretic peptide	Serum B-type natriuretic peptide	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful withdrawal from dobutamine	Successful withdrawal from dobutamine with clinical stability	7 days
Worsening renal function	Increase > 0.3 mg/dL in serum creatinine	7 days
Hyperkalemia	Serum potassium > 5.5 mEq/L	7 days
Hypotension	Systolic blood pressure < 80 mmHg	7 days

Collaborators and Investigators

• Sponsor: InCor Heart Institute
• Investigators: Study Director: Antonio P Barretto, Ph.D., Heart Institute (InCor), University of São Paulo

Publications and helpful links

General Publications

• Ochiai ME, Brancalhao EC, Puig RS, Vieira KR, Cardoso JN, Oliveira MT Jr, Barretto AC. Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial. Clinics (Sao Paulo). 2014;69(5):308-13. doi: 10.6061/clinics/2014(05)02.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Estimate): May 20, 2013
• Last Update Submitted That Met QC Criteria: May 17, 2013
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Hemodynamic; Natriuretic peptide; Vasodilation; Low cardiac output; Renin-aldosterone system
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiac Output, Low; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: INCOR 2993/07/008