Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients

Phase 2

Completed

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

• Registration Number: NCT01922089
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this study is to assess the safety and tolerability of initiating LCZ696 in heart failure patients with reduced ejection fraction (HF-rEF) using conservative (reaching target dose over 6 weeks) and condensed (reaching target dose over 3 weeks) up-titration regimens.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-08-12
• Study First Submitted QC: 2013-08-13
• Study First Posted: 2013-08-14
• Study Start: 2013-11
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Results First Submitted: 2015-07-16
• Status Verified: 2015-09
• Results First Submitted QC: 2015-09-16
• Last Update Submitted: 2015-09-16
• Results First Posted: 2015-10-15
• Last Update Posted: 2015-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 498

Inclusion Criteria

• Age ≥ 18 years; CHF with New York Heart Association class II-IV; left ventricular ejection fraction ≤ 35%; on beta blockers

Exclusion Criteria

• Potassium > 5.2 mmol/l; estimated glomerular filtration rate < 30 ml/min/1.73 m2; systolic blood pressure <100 mmHg or > 180 mmHg; history of intolerance to recommended target doses of angiotensin converting enzyme inhibitors or angiotensin receptor blockers

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LCZ696 Conservative	LCZ696	Up-titration to LCZ696 200 mg bid over 6 weeks
LCZ696 Condensed	LCZ696	Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)	12 weeks	Participants experiencing hypotension, renal dysfunction, hyperkalemia and angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving \> 160 mg of valsartan or \> 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low)	12 weeks	Treatment success was defined as the number of participants who achieved and maintained LCZ696 200 mg bid without any dose interruption or down-titration over 12 weeks and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving \> 160 mg of valsartan or \> 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)
Number of Participants Who Tolerated Study Medication for at Least the Last Two Weeks of the Study and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low).	12 weeks	Tolerability was assessed as the number of participants who achieved LCZ696 200 mg bid and maintained this dose for at least 2 weeks before study completion, regardless of previous dose interruption or down-titration and by Renin-Angiotensin-Aldosterone System (RAAS) stratum (high vs. low) High RAAS stratum Patients receiving \> 160 mg of valsartan or \> 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening Low RAAS stratum: Patients receiving ≤ 160 mg of valsartan or ≤ 10 mg total daily dose of enalapril, or equivalent doses of other ARBs/ACEIs, respectively, at screening. This stratum also included patients who were not on an ACEI or an ARB 4 weeks prior to screening (i.e., ACEI/ARB-naïve patients)

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Nuneaton, United Kingdom