Chronic Heart Failure and Reduced Ejection Fraction (HFrEF)
Conditions
Keywords
Secondary use, Sacubitril Valsartan
Brief summary
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.
Interventions
None listed
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 89 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| association between change in NYHA classification and change in plasma log BNP levels from Baseline | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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. | 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. |
| 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. | 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 |
| change in log-transformed biomarkers from baseline to pre-defined time points | Week 0, Week 4, Week 8, Month 6 | — |
Countries
Japan
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed