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

September 16, 2015 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

498

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Gabrovo, Bulgaria, 5300
        • Novartis Investigative Site
      • Plovdiv, Bulgaria, 4000
        • Novartis Investigative Site
      • Plovdiv, Bulgaria, 4004
        • Novartis Investigative Site
      • Smolian, Bulgaria, 4700
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1407
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1202
        • Novartis Investigative Site
  • Finland
      • Jyvaskyla, Finland, 40620
        • Novartis Investigative Site
      • Tampere, Finland, 33520
        • Novartis Investigative Site
  • Germany
      • Bad Krozingen, Germany, 79189
        • Novartis Investigative Site
      • Berlin, Germany, 10367
        • Novartis Investigative Site
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Berlin, Germany, 10787
        • Novartis Investigative Site
      • Berlin, Germany, 10789
        • Novartis Investigative Site
      • Berlin, Germany, 13347
        • Novartis Investigative Site
      • Berlin, Germany, 13405
        • Novartis Investigative Site
      • Berlin, Germany, 13055
        • Novartis Investigative Site
      • Berlin-Buch, Germany, 13125
        • Novartis Investigative Site
      • Dietzenbach, Germany, 63128
        • Novartis Investigative Site
      • Ebersbach, Germany, 02730
        • Novartis Investigative Site
      • Frankfurt, Germany, 60594
        • Novartis Investigative Site
      • Göttingen, Germany, D-37075
        • Novartis Investigative Site
      • Hassloch, Germany, 67454
        • Novartis Investigative Site
      • Huy / OT Anderbeck, Germany, 38836
        • Novartis Investigative Site
      • Ingelheim, Germany, 55218
        • Novartis Investigative Site
      • Kelkheim, Germany, 65779
        • Novartis Investigative Site
      • Kleve, Germany, 47533
        • Novartis Investigative Site
      • Leipzig, Germany, 04315
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Mainz, Germany, 55116
        • Novartis Investigative Site
      • Mühlheim, Germany, 45468
        • Novartis Investigative Site
      • Siegen, Germany, 57072
        • Novartis Investigative Site
      • Straubing, Germany, 94315
        • Novartis Investigative Site
      • Wuerzburg, Germany, 97078
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1145
        • Novartis Investigative Site
      • Budapest, Hungary, 1042
        • Novartis Investigative Site
      • Budapest, Hungary, H-1096
        • Novartis Investigative Site
      • Debrecen, Hungary, 4032
        • Novartis Investigative Site
      • Mosonmagyarovar, Hungary, 9200
        • Novartis Investigative Site
      • Nyiregyháza, Hungary, 4400
        • Novartis Investigative Site
      • Pecs, Hungary, 7623
        • Novartis Investigative Site
      • Szekesfehervar, Hungary, 8000
        • Novartis Investigative Site
  • Italy
    • AO
      • Aosta, AO, Italy, 11100
        • Novartis Investigative Site
    • AR
      • Cortona, AR, Italy, 52044
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italy, 24128
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • FE
      • Cona, FE, Italy, 44100
        • Novartis Investigative Site
    • RM
      • Albano Laziale, RM, Italy, 00041
        • Novartis Investigative Site
      • Roma, RM, Italy, 00163
        • Novartis Investigative Site
    • SS
      • Sassari, SS, Italy, 07100
        • Novartis Investigative Site
    • TV
      • Vittorio Veneto, TV, Italy, 31029
        • Novartis Investigative Site
    • UD
      • San Daniele Del Friuli, UD, Italy, 33038
        • Novartis Investigative Site
  • Puerto Rico
      • San Juan, Puerto Rico, 00936-6528
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 821 07
        • Novartis Investigative Site
      • Bratislava, Slovakia, 83301
        • Novartis Investigative Site
      • Kosice, Slovakia, 040 01
        • Novartis Investigative Site
      • Lucenec, Slovakia, 98439
        • Novartis Investigative Site
      • Nove Zamky, Slovakia, 940 01
        • Novartis Investigative Site
      • Trebisov, Slovakia, 075 01
        • Novartis Investigative Site
    • Slovak Republic
      • Brezno, Slovak Republic, Slovakia, 977 42
        • Novartis Investigative Site
      • Nitra, Slovak Republic, Slovakia, 949 01
        • Novartis Investigative Site
      • Svidnik, Slovak Republic, Slovakia, 08901
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28007
        • Novartis Investigative Site
    • Andalucia
      • Almeria, Andalucia, Spain, 04120
        • Novartis Investigative Site
      • Malaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
      • Sanlucar de Barrameda, Andalucia, Spain, 11540
        • Novartis Investigative Site
      • Sevilla, Andalucia, Spain, 41014
        • Novartis Investigative Site
    • Cadiz
      • Villamartin, Cadiz, Spain, 11650
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
    • Galicia
      • A Coruna, Galicia, Spain, 15006
        • Novartis Investigative Site
  • Turkey
      • Haydarpasa/Istanbul, Turkey, 34668
        • Novartis Investigative Site
      • Istanbul, Turkey, 34304
        • Novartis Investigative Site
      • Kocaeli, Turkey, 41380
        • Novartis Investigative Site
      • Mersin, Turkey, 33079
        • Novartis Investigative Site
      • Sivas, Turkey, 58140
        • Novartis Investigative Site
  • United Kingdom
      • Bath, United Kingdom, BA1 3NG
        • Novartis Investigative Site
      • Bradford, United Kingdom, BD9 6RJ
        • Novartis Investigative Site
      • Coventry, United Kingdom, CV2 2DX
        • Novartis Investigative Site
      • Harrow, United Kingdom, HA1 3UJ
        • Novartis Investigative Site
      • Nuneaton, United Kingdom, CV10 7DJ
        • Novartis Investigative Site
    • Dorset
      • Dorchester, Dorset, United Kingdom, DT1 2JY
        • Novartis Investigative Site
    • East Sussex
      • St Leonards on Sea, East Sussex, United Kingdom, TN37 7RD
        • Novartis Investigative Site
    • Lancashire
      • Oldham, Lancashire, United Kingdom, OL1 2JH
        • Novartis Investigative Site
    • Tyne and Wear
      • Gateshead, Tyne and Wear, United Kingdom, NE9 6SX
        • Novartis Investigative Site
  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Novartis Investigative Site
    • Arizona
      • Gilbert, Arizona, United States, 85297
        • Novartis Investigative Site
      • Tucson, Arizona, United States, 85710
        • Novartis Investigative Site
    • California
      • Anaheim, California, United States, 92801
        • Novartis Investigative Site
      • Torrance, California, United States, 90502
        • Novartis Investigative Site
    • Florida
      • Atlantis, Florida, United States, 33462
        • Novartis Investigative Site
      • Chiefland, Florida, United States, 32626
        • Novartis Investigative Site
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Novartis Investigative Site
      • Peoria, Illinois, United States, 61602
        • Novartis Investigative Site
    • Indiana
      • Evansville, Indiana, United States, 47714
        • Novartis Investigative Site
    • Louisiana
      • Slidell, Louisiana, United States, 70458
        • Novartis Investigative Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Novartis Investigative Site
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Novartis Investigative Site
    • New York
      • Buffalo, New York, United States, 14215
        • Novartis Investigative Site
      • Laurelton, New York, United States, 11422
        • Novartis Investigative Site
    • Ohio
      • Marion, Ohio, United States, 43302
        • Novartis Investigative Site
    • Tennessee
      • Oak Ridge, Tennessee, United States, 37830
        • Novartis Investigative Site
    • Texas
      • Dallas, Texas, United States, 75231
        • Novartis Investigative Site
      • Houston, Texas, United States, 77030
        • Novartis Investigative Site
      • Houston, Texas, United States, 77094
        • Novartis Investigative Site
      • Livingston, Texas, United States, 77351
        • Novartis Investigative Site
    • Washington
      • Tacoma, Washington, United States, 98405
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LCZ696 Condensed
Up-titration to LCZ696 200 mg twice daily (bid) over 3 weeks
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid
Experimental: LCZ696 Conservative
Up-titration to LCZ696 200 mg bid over 6 weeks
Drug: LCZ696
LCZ696 50 mg/100 mg/200 mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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)
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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)
12 weeks
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
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)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Actual)

August 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

August 12, 2013

First Submitted That Met QC Criteria

August 13, 2013

First Posted (Estimate)

August 14, 2013

Study Record Updates

Last Update Posted (Estimate)

October 15, 2015

Last Update Submitted That Met QC Criteria

September 16, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLCZ696B2228
  • 2013-001835-33 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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