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

Phase 4

Completed

• Conditions: Heart Failure With Reduced Ejection Fraction
• Interventions: Drug: LCZ696

• Registration Number: NCT02661217
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-01-19
• Study First Submitted QC: 2016-01-19
• Study First Posted: 2016-01-22
• Study Start: 2016-02-12
• Primary Completion: 2018-02-20
• Study Completion: 2018-06-20
• Disposition First Submitted: 2019-01-28
• Disposition First Submitted QC: 2019-01-28
• Disposition First Posted: 2019-01-30
• Results First Submitted: 2019-06-20
• Status Verified: 2021-03
• Results First Submitted QC: 2021-03-29
• Last Update Submitted: 2021-03-29
• Results First Posted: 2021-04-26
• Last Update Posted: 2021-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1002

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Post-discharge treatment initiation	LCZ696	Patients received first dose after discharge and up to 14 days thereafter.
Pre-discharge treatment initiation	LCZ696	Patients received first dose at any point after Randomization but no later than 12 h before discharge.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving the Target Dose of LCZ696 200 mg Bid at 10 Weeks Post Randomization	10 weeks after Randomization	Percentage of patients achieving and maintaining LCZ696 200 mg bid for at least 2 weeks leading to Week 10

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Achieving and Maintaining Either LCZ696 100 mg and/or 200 mg Bid	10 weeks after Randomization	Percentage of patients achieving and maintaining either LCZ696 100 mg and/or 200 mg bid for at least 2 weeks leading to Week 10
Percentage of Patients Achieving and Maintaining Any Dose of LCZ696	10 weeks after Randomization	Percentage of patients achieving any dose of LCZ696 for at least 2 weeks leading to 10 weeks of treatment
Percentage of Patients Permanently Discontinued From Treatment	10 weeks after Randomization AND 26 weeks after randomization	Percentage of patients permanently discontinued from LCZ696 (1) up to week 10 due to AEs, and (2) up to week 26 due to any reasons

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 York, United Kingdom