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Exercise Capacity Study of LCZ696 vs. Enalapril in Patients With Chronic Heart Failure and Reduced Ejection Fraction.

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ClinicalTrials.gov Identifier: NCT02768298
Recruitment Status : Recruiting
First Posted : May 11, 2016
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of the study is to determine the effect of LCZ696 vs. Enalapril on improvement of excercise capacity in patients with chronic heart failure with reduced ejection fraction

Condition or disease Intervention/treatment Phase
Chronic Heart Failure With Reduced Ejection Fraction Drug: LCZ696 Drug: enalapril Drug: Enalapril matching placebo Drug: LCZ696 matching placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Active-controlled Study to Assess the Effect of LCZ696 Compared With Enalapril to Improve Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF).
Actual Study Start Date : July 12, 2016
Estimated Primary Completion Date : April 15, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LCZ696
All randomized patients in this arm will be initiated with one tablet of LCZ696 100mg and one tablet of enalapril matching placebo twice a day (bid). Dose will be up-titrated after 2 weeks to the final dose of LCZ696 200mg bid to receive one tablet of LCZ696 200mg and one tablet of enalapril matching placebo twice daily (bid). Patients will be in study drug for 12 weeks.
Drug: LCZ696
LCZ696 50 mg, 100 mg or 200 mg film-coated tablets

Drug: Enalapril matching placebo
Placebo to enalapril 2.5mg, 5 mg and 10 mg film-coated tablets

Active Comparator: Enalapril
All randomized patients in this arm will be initiated with one tablet of Enalapril 5mg and one tablet of LCZ696 matching placebo twice a day (bid). Dose will be up-titrated after 2 weeks to the final dose of Enalapril 10mg bid to receive one tablet of enalapril 10mg and one tablet of LCZ696 200mg matching placebo twice daily (bid). Patients will be in study drug for 12 weeks.
Drug: enalapril
Enalapril 2.5mg, 5 mg and 10 mg film-coated tablets

Drug: LCZ696 matching placebo
Placebo to LCZ696 50mg, 100mg and 200mg film-coated tablets




Primary Outcome Measures :
  1. Change from baseline in peak respiratory oxygen uptake (VO2peak) [ Time Frame: Baseline and 3 months ]
    Cardio-pulmonary-exercise testing (CPET) is an examination of the cardio-pulmonary system using the measurement of respiratory gases during exercise stress. The result provides an overview of cardiopulmonary function, including the measurement of peak oxygen uptake (VO2 peak). CPET to assess VO2peak will be performed at a cycle ergometer during screening (Visit 2) and after 6 weeks and 3 months (Visit 6 and Visit 7).


Secondary Outcome Measures :
  1. Change from baseline in peak respiratory oxygen uptake (VO2peak) [ Time Frame: baseline and 6 weeks ]
    Cardio-pulmonary-exercise testing (CPET) is an examination of the cardio-pulmonary system using the measurement of respiratory gases during exercise stress. The result provides an overview of cardiopulmonary function, including the measurement of peak oxygen uptake (VO2 peak). CPET to assess VO2peak will be performed at a cycle ergometer during screening (Visit 2) and after 6 weeks and 3 months (Visit 6 and Visit 7).

  2. Change from baseline in minute ventilation − carbon dioxide production relationship (VE/VCO2 slope) [ Time Frame: baseline, 6 weeks and 3 months ]
    Cardio-pulmonary-exercise testing (CPET) is an examination of the cardio-pulmonary system using the measurement of respiratory gases during exercise stress. The result provides an overview of cardiopulmonary function, including minute ventilation − carbon dioxide production relationship (VE/VCO2 slope).

  3. Change from baseline in exercise capacity at respiratory exchange ratio of value 1 (RER 1) [ Time Frame: baseline, 6 weeks and 3 months ]

    Cardio-pulmonary-exercise testing (CPET) is an examination of the cardio-pulmonary system using the measurement of respiratory gases during exercise stress. The result provides an overview of cardiopulmonary function, including the respiratory exchange ratio of value 1 (RER 1). RER = carbon dioxide (VCO2)/ respiratory oxygen update (VO2).

    The ratio of carbon dioxide output/oxygen uptake (VCO2/VO2) is called the respiratory exchange ratio (RER). At RER = 1 indicates metabolism primarily of carbohydrates. A change in exercise capacity at peak RER values indicates changes are secondary to the intervention used.


  4. Change from baseline in rate of perceived exertion during exercise [ Time Frame: baseline, 6 weeks and 3 months ]
    The individually experienced excertion (perceived excertion) during cardiopulmonary exercise testing is assessed by Borg scale which is a 15 point scale, starting from 6 which indicates "No exertion at all" to 20 which means "Maximal exertion".



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis of chronic heart failure (NYHA class III) and reduced ejection fraction (LVEF ≤ 40%)
  • Reduced ability to exercise, evidenced by VO2peak ≤ 18 ml/min per kg
  • Patients must be on an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks before study start

Exclusion Criteria:

  • History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs
  • Previous history of intolerance to recommended target doses of ACEIs or ARBs
  • Known history of angioedema
  • Requirement of treatment with both ACEIs and ARBs
  • Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy)
  • Symptomatic hypotension
  • impaired renal function
  • Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02768298


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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Germany
Novartis Investigative Site Recruiting
Regensburg, Bavaria, Germany, 93053
Novartis Investigative Site Recruiting
Dresden, Sachsen, Germany, 01099
Novartis Investigative Site Recruiting
Berlin, Germany, 10117
Novartis Investigative Site Recruiting
Berlin, Germany, 10787
Novartis Investigative Site Recruiting
Berlin, Germany, 13055
Novartis Investigative Site Completed
Berlin, Germany, 13187
Novartis Investigative Site Recruiting
Berlin, Germany, 13405
Novartis Investigative Site Completed
Bonn, Germany, 53115
Novartis Investigative Site Recruiting
Coburg, Germany, 96450
Novartis Investigative Site Recruiting
Dresden, Germany, 01277
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Erfurt, Germany, 99089
Novartis Investigative Site Completed
Essen, Germany, 45356
Novartis Investigative Site Recruiting
Frankfurt, Germany, 60389
Novartis Investigative Site Recruiting
Freiburg, Germany, 79106
Novartis Investigative Site Terminated
Goettingen, Germany, 37075
Novartis Investigative Site Completed
Guetersloh, Germany, 33332
Novartis Investigative Site Recruiting
Hamburg, Germany, 22291
Novartis Investigative Site Recruiting
Hannover, Germany, 30625
Novartis Investigative Site Terminated
Heidelberg, Germany, 69115
Novartis Investigative Site Recruiting
Kiel, Germany, 24105
Novartis Investigative Site Recruiting
Koblenz, Germany, 56068
Novartis Investigative Site Recruiting
Koeln-Nippes, Germany, 50733
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Novartis Investigative Site Recruiting
Koeln, Germany, 51605
Novartis Investigative Site Recruiting
Leipzig, Germany, 04103
Novartis Investigative Site Recruiting
Leverkusen, Germany, 51375
Novartis Investigative Site Recruiting
Ludwigsburg, Germany, 71634
Novartis Investigative Site Recruiting
Ludwigshafen, Germany, 67063
Novartis Investigative Site Completed
Mainz, Germany, 55131
Novartis Investigative Site Completed
Muehlheim An Der Ruhr, Germany, 45468
Novartis Investigative Site Recruiting
Muenchen, Germany, 81675
Novartis Investigative Site Terminated
Mönchengladbach, Germany, 41063
Novartis Investigative Site Recruiting
Neuwied, Germany, 56564
Novartis Investigative Site Terminated
Nienburg, Germany, 31582
Novartis Investigative Site Completed
Oldenburg, Germany, 26133
Novartis Investigative Site Recruiting
Rotenburg an der Fulda, Germany, 36199
Novartis Investigative Site Recruiting
Rüdersdorf, Germany, 15562
Novartis Investigative Site Recruiting
Siegen, Germany, 57072
Novartis Investigative Site Recruiting
Ulm, Germany, 89077
Novartis Investigative Site Recruiting
Villingen-Schwenningen, Germany, 78052
Novartis Investigative Site Recruiting
Worms, Germany, 67550
Novartis Investigative Site Recruiting
Wuerzburg, Germany, 97080
Novartis Investigative Site Completed
Wuppertal, Germany, 42117
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02768298     History of Changes
Other Study ID Numbers: CLCZ696BDE01
2015-004632-35 ( EudraCT Number )
First Posted: May 11, 2016    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Heart failure
systolic heart failure
heart failure with reduced ejection fraction
exercise capacity

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Enalapril
Enalaprilat
LCZ 696
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Angiotensin Receptor Antagonists