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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01922089
First received: August 12, 2013
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure With Reduced Ejection Fraction
Drug: LCZ696
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 499
Study Start Date: November 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Condensed up-titration
Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid
Experimental: Conservative up-titration
Up-titration to LCZ696 200 mg bid over 6 weeks
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01922089

  Show 105 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01922089     History of Changes
Other Study ID Numbers: CLCZ696B2228, 2013-001835-33
Study First Received: August 12, 2013
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Federal Institute for Drugs and Medical Devices
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Slovak Republic: Ethics Committee
Italy: Ministry of Health
Spain: Ministry of Health
Turkey: Ministry of Health
Bulgaria: Ministry of Health
Hungary: Institutional Ethics Committee
Finland: Ministry of Social Affairs and Health
Norway: Norwegian Medicines Agency

Keywords provided by Novartis:
Heart failure, reduced ejection fraction, LCZ696, titration, safety, tolerability

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
3-(1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-3'-methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylmethyl)amino)butyrate
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014