Secondary Use of PARALLEL-HF Data

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: Completed
• Conditions: Chronic Heart Failure and Reduced Ejection Fraction (HFrEF)

• Study Type: Observational
• Enrollment (Actual): 236

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Tokyo, Tokyo, Japan, 105-6333
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
association between change in NYHA classification and change in plasma log BNP levels from Baseline	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

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	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	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.	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.	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		Week 0, Week 4, Week 8, Month 6

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Secondary use; Sacubitril Valsartan
• Other Study ID Numbers: CLCZ696BJP07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO