Tags

Type your tag names separated by a space and hit enter

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.
J Cardiol 2017; 70(3):225-231JC

Abstract

BACKGROUND

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan.

METHODS AND DESIGN

This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial.

CONCLUSIONS

The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan. Electronic address: htsutsui@cardiol.med.kyushu-u.ac.jp.Cardiovascular Division, Jichi Medical University, Saitama Medical Center, Saitama, Japan.First Department of Internal Medicine, Nara Medical University, Kashihara, Japan.Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.Department of Molecular Medicine and Therapeutics, Tottori University, Yonago, Japan.Novartis Pharma K.K., Tokyo, Japan.Novartis Pharma K.K., Tokyo, Japan.Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

28024961

Citation

Tsutsui, Hiroyuki, et al. "Efficacy and Safety of Sacubitril/valsartan (LCZ696) in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction: Rationale for and Design of the Randomized, Double-blind PARALLEL-HF Study." Journal of Cardiology, vol. 70, no. 3, 2017, pp. 225-231.
Tsutsui H, Momomura S, Saito Y, et al. Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study. J Cardiol. 2017;70(3):225-231.
Tsutsui, H., Momomura, S., Saito, Y., Ito, H., Yamamoto, K., Ohishi, T., ... Guo, W. (2017). Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study. Journal of Cardiology, 70(3), pp. 225-231. doi:10.1016/j.jjcc.2016.11.011.
Tsutsui H, et al. Efficacy and Safety of Sacubitril/valsartan (LCZ696) in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction: Rationale for and Design of the Randomized, Double-blind PARALLEL-HF Study. J Cardiol. 2017;70(3):225-231. PubMed PMID: 28024961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study. AU - Tsutsui,Hiroyuki, AU - Momomura,Shinichi, AU - Saito,Yoshihiko, AU - Ito,Hiroshi, AU - Yamamoto,Kazuhiro, AU - Ohishi,Tomomi, AU - Okino,Naoko, AU - Guo,Weinong, Y1 - 2016/12/24/ PY - 2016/07/22/received PY - 2016/10/14/revised PY - 2016/11/02/accepted PY - 2016/12/28/pubmed PY - 2017/12/27/medline PY - 2016/12/28/entrez KW - Heart failure with reduced ejection fraction KW - Japanese KW - LCZ696 KW - Neprilysin KW - Sacubitril/valsartan SP - 225 EP - 231 JF - Journal of cardiology JO - J Cardiol VL - 70 IS - 3 N2 - BACKGROUND: The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. METHODS AND DESIGN: This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. CONCLUSIONS: The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. SN - 1876-4738 UR - https://www.unboundmedicine.com/medline/citation/28024961/Efficacy_and_safety_of_sacubitril/valsartan__LCZ696__in_Japanese_patients_with_chronic_heart_failure_and_reduced_ejection_fraction:_Rationale_for_and_design_of_the_randomized_double_blind_PARALLEL_HF_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0914-5087(16)30309-4 DB - PRIME DP - Unbound Medicine ER -