NCT02188082.

Study name	Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained‐release Tablets (FIRST)
Methods	Study design: Interventional Allocation: Randomised Intervention model: Parallel assignment Masking: Double (participant, investigator) Primary purpose: Treatment Unit of Randomisation: No information Total duration of study: No information Intervention time: 32 weeks Follow‐up: No information Setting: The military general hospital of Beijing PLA; The second affiliated hospital of suzhou university; Subei People's Hospital of Jiangsu province; the First Hospital of Jilin University; shengjing hospital of China medical university; Qilu Hospital of Shandong University; the Second Hospital of Shandong University; The first affiliated hospital of zhejiang university school of medicine; Hangzhou First People's Hospital; The second affiliated hospital of zhejiang university school of medicine; The first affiliated hospital of wenzhou medical university; The second affiliated hospital of wenzhou medical university
Participants	Type of heart failure: Chronic systolic heart failure N = 336 participants Age: 18 to 75 years Gender: Both males and females Inclusion criteria: 1. Aged from 18 to 75 years, males or females 2. Willing to provide written informed consent 3. NYHA class II, III, or IV for ≥ 4 weeks, in stable clinical condition for ≥ 4 weeks 4. Optimised and unchanged chronic heart failure medications and dosages for ≥ 4 weeks 5. Sinus rhythm with resting heart rate ≥ 70 bpm 6. Left‐ventricular systolic dysfunction, with ejection fraction ≥ 40% documented within previous 1 month Exclusion criteria: 1. Unstable cardiovascular condition (e.g. hospital admission for worsening heart failure) 2. Recent (＜ 2 months) myocardial infarction or recent or scheduled coronary revascularisation 3. Stroke or transient cerebral ischaemia within previous 4 weeks 4. Severe primary valvular disease 5. Scheduled surgery of valvular heart disease 6. Active myocarditis 7. Congenital heart diseases 8. Peripartum cardiomyopathy 9. Hyperthyroid heart disease 10. On list for cardiac transplantation 11. Cardiac resynchronisation therapy started within previous 6 months 12. Pacemaker with atrial or ventricular pacing (except biventricular pacing) > 40% of the time, or with stimulation threshold at the atrial or ventricular level > 60 bpm 13. Permanent atrial fibrillation or flutter 14. Sick sinus syndrome, sinoatrial block, second‐ and third‐degree atrio‐ventricular block 15. History of symptomatic or sustained (≥ 30 s) ventricular arrhythmia unless a cardioverter/defibrillator implanted 16. Cardioverter/defibrillator shock within previous 6 months 17. Family history or congenital long QT syndrome or treated with selected QT‐prolonging products (except amiodarone) 18. Contraindication or intolerance to ivabradine or lactulose 19. Severe or uncontrolled hypertension (SBP ≥ 180 mmHg or DBP ≥ 110 mmHg) 20. Known anaemia (haemoglobin ＜ 100 g/L) 21. Known moderate or severe liver disease (ALT/AST > 3ULN), known severe renal disease (Cr > 2ULN) 22. Pregnant or lactating women and women planning to become pregnant 23. Use of an investigational drug within 30 days of enrolment 24. Has a history of psychological illness/condition that interferes with ability to understand or complete requirements of the study
Interventions	Intervention: Ivabradine hemisulfate sustained‐release tablets 5 to 15 mg once a day Comparison: Placebo 5 to 15 mg once a day Concomitant medications: Optimised and unchanged chronic heart failure medications and dosages for ≥ 4 weeks Excluded medications: Use of an investigational drug within 30 days of enrolment
Outcomes	Outcomes measured in the study: Primary outcome: [baseline, week 18] Change from baseline in left ventricular end systolic volume index by ultrasound cardiogram Secondary outcome: [baseline, week 32] Change from baseline in left ventricular end diastolic volume index and left ventricular ejection fraction (LVEF) Incidence of hospital admission for worsening heart failure, any cardiovascular hospital admission, cardiovascular mortality, all‐cause mortality Change from baseline in distance of 6‐minute walking test Change from baseline in heart rate Change from baseline in scores of Kansas City Cardiomyopathy Questionnaire Change from baseline in NT‐pro‐BNP
Starting date	May 2014, recruiting
Contact information	Jianan Wang, Doctor The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou, Zhejiang China 310009 Phone: No information Email: No information
Notes	Primary sponsor: Jiangsu HengRui Medicine Co., Ltd. Ethics status: No information