LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00887588
First received: April 22, 2009
Last updated: August 12, 2015
Last verified: August 2015
Results First Received: July 16, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Chronic Heart Failure
Interventions: Drug: LCZ696
Drug: Valsartan
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 308 participants were randomized to the core 12 week period, but 7 participants were excluded due to major Good Clinical Practice (GCP) violation. Of the 261 participants who completed the core, 252 participants entered the extension period.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eight participants, who completed the core, could not continue in the extension because the 36 week protocol amendment was not yet approved by health authorities; 1 participant, who completed the core, discontinued before the extension start due to an adverse event.

Reporting Groups
  Description
LCZ696 During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
Valsartan During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.

Participant Flow for 2 periods

Period 1:   Core Period
    LCZ696     Valsartan  
STARTED     149     152  
Extension Efficacy Set     127     125  
Full Analysis Set     148     146  
Arterial Stiffness Set     86     94  
COMPLETED     130     131  
NOT COMPLETED     19     21  
Death                 1                 1  
Lost to Follow-up                 3                 1  
Withdrawal by Subject                 6                 8  
Adverse Event                 9                 11  

Period 2:   Extension Period
    LCZ696     Valsartan  
STARTED     127     125  
Arterial Stiffness Set     86     94  
COMPLETED     121     120  
NOT COMPLETED     6     5  
Adverse Event                 4                 4  
Death                 0                 1  
Protocol deviation                 1                 0  
Lost to Follow-up                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
LCZ696 During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.
Valsartan During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.
Total Total of all reporting groups

Baseline Measures
    LCZ696     Valsartan     Total  
Number of Participants  
[units: participants]
  149     152     301  
Age  
[units: Years]
Mean (Standard Deviation)
  70.9  (9.38)     71.2  (8.94)     71.0  (9.15)  
Gender  
[units: Participants]
     
Female     85     85     170  
Male     64     67     131  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)   [ Time Frame: Baseline, 12 weeks ]

2.  Secondary:   Change From Baseline in NT-proBNP and Brain Natriuretic Peptide (BNP)   [ Time Frame: baseline, 36 weeks ]

3.  Secondary:   Change From Baseline in Plasma Cyclic Guanine Monophosphate (cGMP)   [ Time Frame: baseline, 36 weeks ]

4.  Secondary:   Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Relative Wall Thickness, Left Atrial Dimension   [ Time Frame: Baseline, 36 weeks ]

5.  Secondary:   Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume   [ Time Frame: Baseline, 36 weeks ]

6.  Secondary:   Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction   [ Time Frame: Baseline, 36 weeks ]

7.  Secondary:   Change From Baseline in Echocardiography Parameters: Left Ventricular Mass   [ Time Frame: Baseline, 36 weeks ]

8.  Secondary:   Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index   [ Time Frame: Baseline, 36 weeks ]

9.  Secondary:   Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index   [ Time Frame: Baseline, 36 weeks ]

10.  Secondary:   Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus   [ Time Frame: Baseline, 36 weeks ]

11.  Secondary:   Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio   [ Time Frame: Baseline, 36 weeks ]

12.  Secondary:   Change in Echocardiography Parameters: Isovolumic Relaxation Time   [ Time Frame: Baseline, 36 weeks ]

13.  Secondary:   Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity   [ Time Frame: Baseline, 36 weeks ]

14.  Secondary:   Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and Individual Domain Summary Scores   [ Time Frame: baseline, 36 weeks ]

15.  Secondary:   Percentage of Participants With Clinical Composite Assessment of Improved, Unchanged or Worsened   [ Time Frame: 36 weeks ]

16.  Secondary:   Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV   [ Time Frame: baseline, 36 weeks ]

17.  Secondary:   Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)   [ Time Frame: baseline, 36 weeks ]

18.  Secondary:   Change From Baseline in Serum Creatinine   [ Time Frame: baseline, 36 weeks ]

19.  Secondary:   Change From Baseline in Albumin/Creatinine Ratio   [ Time Frame: baseline, 36 weeks ]

20.  Secondary:   Change From Baseline in Arterial Stiffness Parameters: Brachial Systolic Blood Pressure (SBP), Brachial Diastolic Blood Pressure (DBP), Central Augmentation Pressure, Central Pressure at T1-DP, Central SBP, Central DBP, Central Mean Pressure   [ Time Frame: baseline, 36 weeks ]

21.  Secondary:   Change From Baseline in Arterial Stiffness Parameters: Heart Rate Correct Cen Aug/Pulse Ht   [ Time Frame: baseline, 36 weeks ]

22.  Secondary:   Change From Baseline in Arterial Stiffness Parameters: Heart Rate   [ Time Frame: baseline, 36 weeks ]

23.  Secondary:   Change From Baseline in Arterial Stiffness Parameters: Pulse Wave Velocity   [ Time Frame: baseline, 36 weeks ]

24.  Secondary:   Change From Baseline in Sitting SBP, Sitting DBP and Sitting Pulse Pressure (PP)   [ Time Frame: baseline, 36 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


Publications:
Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00887588     History of Changes
Other Study ID Numbers: CLCZ696B2214, 2009-010208-27
Study First Received: April 22, 2009
Results First Received: July 16, 2015
Last Updated: August 12, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Brazil: Ministry of Health
Canada: Health Canada
India: Ministry of Health
Italy: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Poland: Ministry of Health
Romania: Ministry of Public Health
Russia: Pharmacological Committee, Ministry of Health
Singapore: Health Sciences Authority
Spain: Ministry of Health
Venezuela: Ministry of Health and Social Development
Germany: Federal Institute for Drugs and Medical Devices