Trial · NCT02468232
Study of Efficacy and Safety of LCZ696 in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction
NCT02468232, Phase 3, Completed, Novartis Pharmaceuticals; results first posted 2023-12-08
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Study of Efficacy and Safety of LCZ696 in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction. Trials, record NCT02468232. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02468232
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Study of Efficacy and Safety of LCZ696 in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction
- NCT number
- NCT02468232
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 225 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Heart Failure With Reduced Ejection Fraction (HF-rEF)
- Interventions
- LCZ696, Enalapril, Placebo to LCZ696, Placebo to Enalapril
- First posted
- 2015-06-10
- Last updated
- 2023-12-08
- Results first posted
- 2023-12-08
Source ClinicalTrials.gov
Registered outcomes27
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | up to 40 months | Composite endpoint is defined as either cardiovascular (CV) death or heart failure (HF) hospitalization in Japanese patients with chronic heart failure (CHF) and reduced ejection fraction. The composite endpoint events occurred on and after End-of-study (EOS) declaration were reported by investigators but those events were not required to be adjudicated by Clinical Endpoint Committee (CEC) and not included in the efficacy analysis. |
| Primary | Exposure-adjusted Incident Rate (EAIR) of CEC Confirmed Composite Endpoints | up to 40 months | Composite endpoint is defined as either cardiovascular (CV) death or heart failure (HF) hospitalization in Japanese patients with chronic heart failure (CHF) and reduced ejection fraction. EAIR = n/T where n = Total number of events included in the analysis. T (100 patient years) = total up-to-event/censoring duration-time summarized over participants in the respective treatment group. The composite endpoint events occurred on and after EOS declaration were reported by investigators but those events were not required to be adjudicated by CEC and not included in the efficacy analysis. |
| Secondary | Key Secondary: Change From Baseline to the Pre-defined Time-points in Log-transformed Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Baseline, Weeks 4, 8 and Month 6 | NT-proBNP is small protein produced in large amounts when the heart senses it needs to work harder, such as in heart failure. Change from baseline to the pre-defined time-points in logarithmic scale were analyzed using a repeated measures ANCOVA model with treatment, the stratification factor screening NT-proBNP classification recorded in the Interactive Web Response System (IWRS), visit and treatment-by-visit interaction as fixed effect factors and the logarithmic baseline biomarker value as a covariate, with a common unstructured covariance matrix among visits for each treatment. The analysis is using all available data up to month 6 based on likelihood method with an assumption of missing at random (MAR) for missing data. This record summarizes the estimates of ratio Post-baseline /Baseline NT-proBNP. |
| Secondary | Key Secondary: Number of Participants With CEC-confirmed First Triple Composite Endpoint (Cardiovascular (CV) Death, Heart Failure (HF) Hospitalization, or Worsening of HF in Outpatients) | up to 40 months | Composite endpoint is defined as either cardiovascular (CV) death or heart failure (HF) hospitalization in Japanese patients with chronic heart failure (CHF) and reduced ejection fraction. Worsening HF defined as: worsening signs and symptoms of HF requiring addition of a new drug for HF treatment, initiation of IV treatment, increase of diuretic dose for persistent use for ≥4 consecutive weeks, or institution of mechanical or circulatory support such as mechanical ventilation, ultrafiltration, hemodialysis, intra-aortic balloon pump or ventricular assist device. The composite endpoint events occurred on and after EOS declaration were reported by investigators but those events were not required to be adjudicated by CEC and not included in the efficacy analysis. |
| Secondary | Key Secondary: EAIR of CEC-confirmed First Triple Composite Endpoint (Cardiovascular (CV) Death, Heart Failure (HF) Hospitalization, or Worsening of HF in Outpatients) | up to 40 months | Worsening HF defined as: worsening signs and symptoms of HF requiring addition of a new drug for HF treatment, initiation of IV treatment, increase of diuretic dose for persistent use for ≥4 consecutive weeks, or institution of mechanical or circulatory support such as mechanical ventilation, ultrafiltration, hemodialysis, intra-aortic balloon pump or ventricular assist device. EAIR(Exposure-adjusted incidence rate per 100 patient years)= n/T: n: Total number of events included in the analysis. T(100 patient years): total up-to-event/censoring duration-time summarized over patients in the respective treatment group. The composite endpoint events occurred on and after EOS declaration were reported by investigators but those events were not required to be adjudicated by CEC and not included in the efficacy analysis. |
| Secondary | Key Secondary: Number of Participants by Changes in New York Heart Association (NYHA) Classification From Baseline at Predefined Timepoints | Baseline, Weeks 4, 8 and Month 6 | NYHA classification is a subjective physician's assessment of heart failure patient's functional capacity and symptomatic status. Class I - No limitation of physical activity. Class II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). Class III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV - Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. The NYHA class change was analyzed as a three category ordinal variable with levels: "improved", "unchanged", and "worsened", defined by at least one class improvement, no change, at least one class worsening, in NYHA class, respectively. NYHA class after patients who died was categorized into "worsened". |
| Secondary | Key Secondary: Change From Baseline in Clinical Summary Score for Heart Failure Symptoms and Physical Limitations Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). | Baseline, Week 8 and Month 6 | The KCCQ is a self-administered questionnaire and requires, on average, 4-6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL), each with different Likert scaling wording, including limitations, frequency, bother, change in condition, understanding, etc. The clinical summary score is a mean of the physical limitation and total symptom scores. The total symptom score is the mean of the symptom frequency and symptom burden scores. Each scale score (the physical limitation, symptom frequency or symptom burden) is calculated as the mean of its item scores and transformed to a 0-100 scale, with higher score indicating higher level of functioning. A score of 100 represents perfect health whereas a score of 0 represents dead. A change of 5 points on the scale scores, either as a group mean difference or an intra-individual change appears to be clinically significant. |
| Secondary | Total Number of CEC Confirmed Composite of CV Death and Total (First and Recurrent) HF Hospitalizations for Heart Failure | up tp 40 months | Total number of CEC-confirmed CV death and total (first and recurrent) HF hospitalizations per patient was analyzed using the negative binomial regression model. CV deaths and HF hospitalizations occurred on and after EOS declaration were reported by investigators but those events were not required to be adjudicated by CEC and not included in the efficacy analysis. |
| Secondary | Number of Participants by Changes in Clinical Composite Score (as Assessed by NYHA Classification and Patient Global Assessment) at Predefined Timepoints | Baseline, Month 6 | The global assessment was derived from the 7-category classification of the global assessment of disease activity to a three-category classification: Improved (Markedly improved; moderately improved), Unchanged (Slightly improved, unchanged, slightly worsened), and Worsened (Moderately worsened, markedly worsened). The clinical composite assessment was defined as follows: * Improved: 1) If NYHA class decreased at least one level and Global Assessment was not worse at the selected visit and there was no major AE up to the selected visit; or 2) Global assessment was improved and NYHA class did not increase at the selected visit, and there was no major AE up to the selected visit. * Worsened: 1) If NYHA class increased at the selected visit; or 2) Global Assessment was worse at the selected visit; or 3) experienced a major AE up to the selected visit. * Unchanged: If neither "Improved" nor "Worsened". |
| Secondary | Number of Participants With All-cause Mortality | up to 40 months | The number of participants who died due to any cause. Deaths occurred on and after EOS declaration were reported by investigators but those events were not required to be adjudicated by CEC and not included in the efficacy analysis. |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 registered outcomesOutcomes27
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | up to 40 months | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Exposure-adjusted Incident Rate (EAIR) of CEC Confirmed Composite Endpoints | up to 40 months | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. | Events per 100 patient-years | NUMBER |
| SECONDARY | Key Secondary: Change From Baseline to the Pre-defined Time-points in Log-transformed Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) | Baseline, Weeks 4, 8 and Month 6 | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study.~This analysis is a longitudinal data analysis and all available data up to month 6 for each patient was used. Number of participants at each post-time point indicates the number of patients who have both baseline and post-time point values. | ratio | GEOMETRIC_MEAN |
| SECONDARY | Key Secondary: Number of Participants With CEC-confirmed First Triple Composite Endpoint (Cardiovascular (CV) Death, Heart Failure (HF) Hospitalization, or Worsening of HF in Outpatients) | up to 40 months | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Key Secondary: EAIR of CEC-confirmed First Triple Composite Endpoint (Cardiovascular (CV) Death, Heart Failure (HF) Hospitalization, or Worsening of HF in Outpatients) | up to 40 months | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. | Events per 100 patient-years | NUMBER |
| SECONDARY | Key Secondary: Number of Participants by Changes in New York Heart Association (NYHA) Classification From Baseline at Predefined Timepoints | Baseline, Weeks 4, 8 and Month 6 | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. Number of participants at post-time point (i.e., n) indicates the number of patients who have post-time point values. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Key Secondary: Change From Baseline in Clinical Summary Score for Heart Failure Symptoms and Physical Limitations Assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). | Baseline, Week 8 and Month 6 | FAS consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. FAS included all patients with at least one KCCQ data. This is a longitudinal data analysis and all available data for each patient was used. Number of patients at each post-time point (n) indicates the number of patients who have both baseline and post-time point values. | scores on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Total Number of CEC Confirmed Composite of CV Death and Total (First and Recurrent) HF Hospitalizations for Heart Failure | up tp 40 months | The Full Analysis Set (FAS) consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. | Events per patient | NUMBER |
| SECONDARY | Number of Participants by Changes in Clinical Composite Score (as Assessed by NYHA Classification and Patient Global Assessment) at Predefined Timepoints | Baseline, Month 6 | The Full Analysis Set (FAS) consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. Overall Number of Participants Analyzed' indicates the number of patients who have post-time point values. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With All-cause Mortality | up to 40 months | The Full Analysis Set (FAS) consists of all randomized patients with the exception for those patients who have not been qualified for randomization and have not received investigational drug, but have been inadvertently randomized into the study. | Participants | COUNT_OF_PARTICIPANTS |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 outcomesResults by group154
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | LCZ696 | Primary composite | 30 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | Enalapril | Primary composite | 28 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | LCZ696 (Core) OLE Epoch | Primary composite | 0 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | Enalapril (Core) OLE Epoch | Primary composite | 0 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | LCZ696 | Cardiovascular (CV) Death | 13 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | Enalapril | Cardiovascular (CV) Death | 11 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | LCZ696 (Core) OLE Epoch | Cardiovascular (CV) Death | 0 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | Enalapril (Core) OLE Epoch | Cardiovascular (CV) Death | 0 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | LCZ696 | 1st heart failure (HF) Hospitalization | 25 | Participants | |
| Number of Participants Who Had CEC (Clinical Endpoint Committee) Confirmed Composite Endpoints | Enalapril | 1st heart failure (HF) Hospitalization | 20 | Participants |
1 to 10 of 154Source ClinicalTrials.gov
See all 154 results by groupParticipant flow40
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Core Part of Study | STARTED | LCZ696 | 112 | |
| Core Part of Study | STARTED | Enalapril | 113 | |
| Core Part of Study | STARTED | LCZ696 (Core) OLE Epoch | 0 | |
| Core Part of Study | STARTED | Enalapril (Core) OLE Epoch | 0 | |
| Core Part of Study | Randomized Patients | LCZ696 | 112 | |
| Core Part of Study | Randomized Patients | Enalapril | 113 | |
| Core Part of Study | Randomized Patients | LCZ696 (Core) OLE Epoch | 0 | |
| Core Part of Study | Randomized Patients | Enalapril (Core) OLE Epoch | 0 | |
| Core Part of Study | Mis-randomized Patients | LCZ696 | 1 | |
| Core Part of Study | Mis-randomized Patients | Enalapril | 1 |
1 to 10 of 40Source ClinicalTrials.gov
See all 40 participant flowAdverse events2,796
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | LCZ696 | 11 | 111 | |
| other | Anaemia | Blood and lymphatic system disorders | Enalapril | 11 | 112 | |
| other | Anaemia | Blood and lymphatic system disorders | LCZ696 (Core) OLE Epoch | 6 | 79 | |
| other | Anaemia | Blood and lymphatic system disorders | Enalapril (Core) OLE Epoch | 2 | 71 | |
| other | Anaemia macrocytic | Blood and lymphatic system disorders | LCZ696 | 0 | 111 | |
| other | Anaemia macrocytic | Blood and lymphatic system disorders | Enalapril | 0 | 112 | |
| other | Anaemia macrocytic | Blood and lymphatic system disorders | LCZ696 (Core) OLE Epoch | 1 | 79 | |
| other | Anaemia macrocytic | Blood and lymphatic system disorders | Enalapril (Core) OLE Epoch | 0 | 71 | |
| other | Anaemia of malignant disease | Blood and lymphatic system disorders | LCZ696 | 0 | 111 | |
| other | Anaemia of malignant disease | Blood and lymphatic system disorders | Enalapril | 1 | 112 |
1 to 10 of 2,796Source ClinicalTrials.gov
See all 2,796 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | LCZ696 | 20 | 111 |
| Total, all-cause mortality | Enalapril | 17 | 112 |
| Total, all-cause mortality | LCZ696 (Core) OLE Epoch | 4 | 79 |
| Total, all-cause mortality | Enalapril (Core) OLE Epoch | 3 | 71 |
| Total, other adverse events | LCZ696 | 108 | 111 |
| Total, other adverse events | Enalapril | 108 | 112 |
| Total, other adverse events | LCZ696 (Core) OLE Epoch | 67 | 79 |
| Total, other adverse events | Enalapril (Core) OLE Epoch | 64 | 71 |
| Total, serious adverse events | LCZ696 | 64 | 111 |
| Total, serious adverse events | Enalapril | 61 | 112 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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The record and each of its lists are JSON, twenty rows a page. No key.
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GET https://conductscience.org/api/trials/v1/NCT02468232/registered?page=2