Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients (TITRATION)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01922089
First received: August 12, 2013
Last updated: September 16, 2015
Last verified: September 2015

August 12, 2013
September 16, 2015
November 2013
August 2014   (final data collection date for primary outcome measure)
Number of Participants Experiencing Hypotension, Renal Dysfunction, Hyperkalemia and Angioedema and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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)
  • Percentage of patients experiencing specified adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of patients with systolic blood pressure < 95 mmHg [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of patients with abnormal serum creatinine and doubling of serum creatinine [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of patients with Serum potassium > 5.5 mmol/l and ≥ 6.0 mmol/l [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01922089 on ClinicalTrials.gov Archive Site
  • Number of Participants Who Achieved Treatment Success Over the 12 Weeks and by Renin-Angiotensin-Aldosterone System (RAAS) Stratum (High vs. Low) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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)
  • Percentage of patients who achieve treatment success [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients who tolerate study medication for at least the last two weeks of the study [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
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Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients
A Multicenter, Randomized, Double-blind, Parallel Group Study to Assess the Safety and Tolerability of Initiating LCZ696 in Heart Failure Patients Comparing Two Titration Regimens
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Heart Failure With Reduced Ejection Fraction
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid
  • Experimental: LCZ696 Condensed
    Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks
    Intervention: Drug: LCZ696
  • Experimental: LCZ696 Conservative
    Up-titration to LCZ696 200 mg bid over 6 weeks
    Intervention: Drug: LCZ696
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
498
August 2014
August 2014   (final data collection date for primary outcome measure)

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.

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Bulgaria,   Finland,   Germany,   Hungary,   Italy,   Puerto Rico,   Slovakia,   Spain,   Turkey,   United Kingdom
Norway
 
NCT01922089
CLCZ696B2228, 2013-001835-33
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP