Clinical trial NCT02188082: Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets （FIRST）
Official title: Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets （FIRST）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Chronic Systolic Heart Failure
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-07-11
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Ivabradine acts by inhibiting the ionic If current that modulates the pacemaker activity of sinoatrial node cells. The aim of present study is to evaluate the efficacy and safety of IvabRadine hemisulfate Sustained-release Tablets versus placebo in patients with moderate to severe chronic systolic heart failure.


Eligibility criteria: Inclusion Criteria:

* aged from 18 to 75 years, males or females
* Willing to provide written informed consent
* NYHA Class II, III, or IV for≥4 weeks, in stable clinical condition for

  ≥4 weeks
* Optimized and unchanged chronic heart failure medications and dosages for≥4 weeks
* Sinus rhythm with resting heart rate≥70 b.p.m.
* Left-ventricular systolic dysfunction, with ejection fraction≥40% documented within previous 1 month

Exclusion Criteria:

* Unstable cardiovascular condition(for example, hospital admission for worsening heart failure)
* Recent (\<2 months) myocardial infarction or recent or scheduled coronary revascularization
* Stroke or transient cerebral ischaemia within previous 4 weeks
* Severe primary valvular disease
* Scheduled surgery of valvular heart disease
* Active myocarditis
* Congenital heart diseases
* peripartum cardiomyopathy
* hyperthyroid heart disease
* On list for cardiac transplantation
* Cardiac resynchronization therapy started within previous 6 months
* Pacemaker with atrial or ventricular pacing (except biventricular pacing)˃40% of the time, or with stimulation threshold at the atrial or ventricular level˃60 b.p.m.
* Permanent atrial fibrillation or flutter
* Sick sinus syndrome, sinoatrial block, second and third degree atrio-ventricular block
* History of symptomatic or sustained (≥30 s) ventricular arrhythmia unless a cardioverter/defibrillator implanted
* Cardioverter/defibrillator shock within previous 6 months
* Family history or congenital long QT syndrome or treated with selected QT-prolonging products(except amiodarone)
* Contraindication or intolerance to ivabradine or lactulose
* Severe or uncontrolled hypertension (SBP≥180 mmHg or DBP≥110 mmHg)
* known anaemia(Hb\<100 g/L)
* Known moderate or severe liver disease(ALT/AST˃3ULN), known severe renal disease(Cr˃2ULN)
* Pregnant or lactating women and women planning to become pregnant
* Use of an investigational drug within 30 days of enrollment
* Has a history of psychological illness/condition that interferes with ability to understand or complete requirements of the study

Primary outcomes:
measure: Change From Baseline in Left Ventricular End Systolic Volume Index by ultrasound cardiogram
timeFrame: baseline and week 32
Secondary outcomes:
measure: Change From Baseline in Left Ventricular End Diastolic Volume Index and left ventricular ejection fraction(LVEF)
timeFrame: baseline and week 32
measure: incidence of hospital admission for worsening heart failure、any cardiovascular hospital admission、 cardiovascular mortality、all-cause mortality
timeFrame: baseline and week 32
measure: change from baseline in distance of 6-minute walking test
timeFrame: baseline and week 32
measure: change from baseline in heart rate
timeFrame: baseline and week 32
measure: change from baseline in scores of Kansas City Cardiomyopathy Questionnaire
timeFrame: baseline and week 32
measure: change from baseline in NT-proBNP
timeFrame: baseline and week 32
Other outcomes:
Locations:
city: Beijing
country: China
facility: The military general hospitla of Beijing PLA
state: Beijing
city: Suzhou
country: China
facility: The second affiliated hospital of suzhou university
state: Jiangsu
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu province
state: Jiangsu
city: Changchun
country: China
facility: the First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: shengjing hospital of China medical university
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jinan
country: China
facility: the Second Hospital of Shandong University
state: Shandong
city: Hangzhou
country: China
facility: The first affiliated hospital of zhejiang university school of medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Hangzhou First People'S Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The second affiliated hospital of zhejiang university school of medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The first affiliated hospital of wenzhou medical university
state: Zhejiang
city: Wenzhou
country: China
facility: The second affiliated hospital of wenzhou medical university
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Jianan Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ye F, Wang X, Wu S, Ma S, Zhang Y, Liu G, Liu K, Yang Z, Pang X, Xue L, Lu S, Zhong M, Li J, Yu H, Lou D, Cui D, Xie X, Wang J; FIRST Investigators. Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure. J Am Coll Cardiol. 2022 Aug 9;80(6):584-594. doi: 10.1016/j.jacc.2022.05.027.