Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION)

Novartis

Status and phase: Completed; Phase 4

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Drug: LCZ696

Study type: Interventional

Funder types: Industry

Identifiers

NCT02661217

CLCZ696B2401

2015-003266-87 (EudraCT Number)

Details and patient eligibility

About

To explore two modalities of treatment initiation (Pre-discharge, and Post-discharge) with LCZ696 in HFrEF patients following stabilization after an ADHF episode.

Enrollment: 1,002 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients hospitalized due to acute decompensated HF episode (ADHF) as primary diagnosis) and consistent Signs & Symptoms

2. Diagnosis of HF New York Heart Association class II-to-IV and reduced ejection fraction: Left ventricular ejection fraction ≤ 40% at Screening

3. Patients did not receive any IV vasodilators (except nitrates), and/or any IV inotropic therapy from the time of presentation for ADHF to Randomization

4. Stabilized (while in the hospital) for at least 24 hours leading to Randomization.

5. Meeting one of the following criteria:

   • Patients on any dose of ACEI or ARB at screening
   • ACEI/ARB naïve patients and patients not on ACEI or ARB for at least 4 weeks before screening.

Exclusion criteria

1. History of hypersensitivity to the sacubitril, valsartan, or any ARBs, NEP inhibitors or to any of the LCZ696 excipients.
2. Symptomatic hypotension and/or a SBP below 110 mm Hg or SBP above 180 mm Hg prior to randomization
3. End stage renal disease at Screening; or estimated GFR below 30 mL/min/1.73 m2 (as measured by MDRD formula at Randomization.
4. Serum potassium above 5.4 mmol/L at Randomization.
5. Known history of hereditary or idiopathic angioedema or angioedema related to previous ACE inhibitor or ARB therapy
6. Severe hepatic impairment, biliary cirrhosis and cholestasis

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,002 participants in 2 patient groups

Pre-discharge treatment initiation

Other group

Description:

Patients received first dose at any point after Randomization but no later than 12 h before discharge.

Treatment:

Drug: LCZ696

Post-discharge treatment initiation

Other group

Description:

Patients received first dose after discharge and up to 14 days thereafter.

Treatment:

Drug: LCZ696