Secondary Use of PARALLEL-HF Data

April 7, 2026 updated by: Novartis Pharmaceuticals

Brain Natriuretic Peptide and Biomarkers of Heart Failure During Sacubitril Valsartan Treatment in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction (HFrEF): Secondary Use of PARALLEL-HF Data

This study utilized the blood and first morning void (FMV) urine samples from the PARALLEL-HF study (core part). The PARALLEL-HF study (core part) was a multicenter, randomized, double-blind, double-dummy, parallel-group, active-controlled study to assess the effect of sacubitril valsartan at a target dose of 200 mg b.i.d. and enalapril 10 mg b.i.d. on cardiovascular (CV) mortality and morbidity in Japanese HF patients with reduced ejection fraction.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
236

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

  • Japan
    • Tokyo
      • Tokyo, Tokyo, Japan, 105-6333
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Data related to biomarkers and clinical assessment in the PARALLEL-HF study

Description

Inclusion Criteria:

  1. Written informed consent was required before any assessment could be performed.
  2. Male or female outpatients of ≥ 20 years of age (at the time of signing informed consent)

  3. Patients with a diagnosis of congestive heart failure NYHA class II-IV and reduced ejection fraction:

    • LVEF ≤ 35% at Visit 1
    • NT-proBNP ≥ 600 pg/mL at Visit 1 OR NT-proBNP ≥ 400 pg/mL at Visit 1 and a hospitalization for HF within the previous 12 months
  4. Patients were to be on an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) at a stable dose for at least 4 weeks before Visit 1.
  5. Patients were to be treated with a β-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks prior to Visit 1.
  6. An aldosterone antagonist was also to be considered in all patients, taking account of renal function, serum potassium and tolerability. If given, the dose of aldosterone antagonist was to be optimized according to guideline recommendations and patient tolerability, and should be stable for at least 4 weeks prior to Visit 1. Other evidence-based therapy for HF was also to be considered e.g., cardiac resynchronization therapy and an implantable cardioverter-defibrillator in selected patients, as recommended by guidelines.

Exclusion Criteria:

  1. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes, ACEIs, ARBs, neutral endopeptidase (NEP) inhibitors as well as known or suspected contraindications to the study drugs.
  2. Previous documented history of intolerance to ACEIs or ARBs.
  3. Known history of angioedema.
  4. Requirement of treatment with both ACEIs and ARBs.
  5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy).
  6. Symptomatic hypotension and/or a systolic blood pressure (SBP) < 100 mmHg at Visit 1 (Screening) or < 95 mmHg at Visit 199 (end of run-in).
  7. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as measured by the Japanese formula at Visit 1 (Screening) or Visit 199 (end of run-in) or > 35% decline in eGFR between Visit 1 and Visit 199 (according to local measurements).
  8. Serum potassium > 5.2 mmol/L (mEq/L) at Visit 1 (Screening) or > 5.4 mmol/L (mEq/L) at Visit 199 (end of run-in) (according to local measurements).
  9. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1.
  10. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1.
  11. Implantation of a cardiac resynchronization therapy pacemaker (CRT-P) or a cardiac resynchronization therapy defibrillator (CRT-D) or upgrading of an existing conventional pacemaker or an implantable cardioverter defibrillator (ICD) to CRT device within 3 months prior to Visit 1 or intent to implant such a device. Also, patients who had implantation of a conventional pacemaker or an ICD or had a revision of a pacemaker or other device leads within 1 month before Visit 1 are excluded.
  12. History of severe pulmonary disease.

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
association between change in NYHA classification and change in plasma log BNP levels from Baseline
Time Frame: Baseline, Month 6, Week 0, Week 4 and Week 8
In this study, response variable change from Baseline in NYHA class was grouped into 3 categories: improved=3 unchanged=2 and worsened=1. An ordinal logistic regression model was used to assess the relationship between change from Baseline in NYHA classification and log-transformed change from Baseline of (BNP).
Baseline, Month 6, Week 0, Week 4 and Week 8

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
association between the change in NYHA classification and log-transformed biomarkers from Baseline to pre-defined time points in patients treated with either sacubitril valsartan or enalapril
Time Frame: Week 0, Week 4, Week 8, Month 6
The response variable was the change from baseline in NYHA class (expressed as improved, unchanged, worsened). The model included baseline NYHA class as fixed effects and log-transformed change from baseline of biomarkers (BNP, cGMP, UACR, aldosterone, hsTnT, Cys-C, PRA, NT-proBNP, hsCRP) at any scheduled timepoints as covariates.
Week 0, Week 4, Week 8, Month 6
association between the change in KCCQ-CSS and log-transformed biomarkers from Baseline to pre-defined time points in patients treated with either sacubitril valsartan or enalapril
Time Frame: Week 0, Week 4, Week 8, Month 6
The binary response analysis was performed using a generalized mixed model with baseline KCCQ-CSS as fixed effects and log-transformed change from baseline of biomarkers (BNP, cGMP, UACR, aldosterone, hsTnT, Cys-C, PRA, NT-proBNP, hsCRP) as covariates.
Week 0, Week 4, Week 8, Month 6
association between the change in NYHA classification from Baseline to pre-defined time points and Baseline of log-transformed biomarkers in patients treated with either sacubitril valsartan or enalapril.
Time Frame: Week 0, Week 4, Week 8, Month 6
The response variable is the change from baseline in NYHA class (expressed as improved, unchanged, worsened). The model includes baseline NYHA class as fixed effects and log-transformed baseline of biomarkers (BNP, cGMP, UACR, aldosterone, hsTnT, Cys-C, PRA, NT-proBNP, hsCRP) at any scheduled timepoints as covariates.
Week 0, Week 4, Week 8, Month 6
association between the change in KCCQ from Baseline to pre-defined time points and Baseline of log-transformed biomarkers in patients treated with either sacubitril valsartan or enalapril.
Time Frame: Week 0, Week 4, Week 8, Month 6
The binary response analysis is performed using a generalized mixed model with baseline KCCQ-OSS as fixed effects and log-transformed baseline of biomarkers (BNP, cGMP, UACR, aldosterone, hsTNT, Cys-C, PRA, NT-proBNP, hsCRP) as covariates
Week 0, Week 4, Week 8, Month 6
change in log-transformed biomarkers from baseline to pre-defined time points
Time Frame: Week 0, Week 4, Week 8, Month 6
Week 0, Week 4, Week 8, Month 6

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 27, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLCZ696BJP07

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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