evaluating iron protein succinylate oral solution in treating chronic heart failure and iron deficiency

Conditions: Chronic Heart Failure; Iron-deficiency

Summary: this study aims to evaluate the effect of standard heart failure therapy plus oral solution with protein succinylate iron compared to placebo on the primary end point of 6 minute walk distance at 24th week in patients with chronic ejection fraction reduction heart failure and iron deficiency.

this clinical trial was designed as a multicenter, prospective, randomized, double-blind controlled study. patients were randomly divided into one of two treatment groups: control group: standard treatment + placebo（1 bottle orally, twice daily, take orally before meals, duration of treatment 16-24 weeks）. test group: standard treatment + iron protein succinylate oral solution (1 bottle orally, twice daily, take orally before meals, duration of treatment 16-24 weeks）. sample size calculation is according to the change of 6 minute walk distance from the baseline at 24 weeks, it is estimated the mean difference between two groups is 20 meter, standard deviation 80 meter, statistical power 80%, type i error 0.05, follow up loss 15%，estimated total sample size 600.

Eligibility criteria:
inclusion criteria: 1. sign informed consent form; 2. between 18 to 80 years old, male or female; 3. patients with chronic ejection fraction reduction heart failure, has been accepted the medication recommended by the guidelines for treatment of heart failure in china (2014) for at least 4 weeks (that comply with the following requirements): if there is no contraindications or intolerance, patients should receive the renin angiotensin aldosterone system inhibitors, b blockers, and no dose adjustment within 4 weeks (not including diuretics). for patients who do not follow the guidelines for the use and titration of the renin angiotensin aldosterone system inhibitor and b blocker drugs, the cause should be recorded; 4. lvef\< 40% (determined by simpson method) (valid for one week before randomization); 5. nyha heart function ii-iii grade; 6. nt-probnp\>400pg/ml, it should be .900pg/ml at atrial fibrillation; 7. upper limit of hemoglobin: women less than 120g/l, men less than 130g/l. lower limit of hemoglobin: more than 90g/l for both men and women. accompanied by iron deficiency (iron deficiency is defined as serum ferritin\<100ug/l, or serum ferritin between 100\~300ug/l with transferrin saturation (tsat) \<20%); 8. capable of 6 minute walk test. exclusion criteria: 1. patients with significant bleeding: gastrointestinal bleeding, menorrhagia, history of gastrointestinal bleeding and no evidence of gastrointestinal disease healing; 2. history of oral iron supplementation and intolerance; 3. history of acquired iron overload; 4. exclude if receiving erythropoietin, intravenous iron, transfusion therapy and oral iron (including iron contained in compound vitamins or other compound medicine) ≧75mg/day within 6 weeks before enrollment; 5. patients in urgent need of blood transfusion; 6. vtaminb12 and/or folate deficiency, unless correctable; and non-iron deficiency anemia; 7. severe renal insufficiency（egfr \< 20ml/min/1.73m2, mdrd formula）, renal anemia; or history of kidney dialysis, need of kidney dialysis at present or in 6 months; 8. chronic liver disease, cirrhosis, active hepatitis, transaminases (increase of alanine aminotransferase and aspartate aminotransferase 3 times above the normal upper limit. total bilirubin 3 times higher than the normal upper limit); 9. intestinal diseases which affect iron absorption such as inflammatory bowel disease and chronic pancreatitis; 10. active infection; 11. history of syncope within 3 months, diagnosed as cardiogenic shock over the past 1 months; 12. active myocarditis, constrictive pericarditis and other pericardial diseases; 13. acute decompensated heart failure with unstable hemodynamics; 14. symptomatic bradycardia or second or third-degree cardiac conduction block with no pacemaker installed; 15. severe chronic obstructive pulmonary disease, pulmonary heart disease, severe pulmonary vascular disease, pulmonary hypertension caused by autoimmune diseases and any type of severe pulmonary hypertension; 16. valvular heart disease and congenital heart disease without operation; hypertrophic cardiomyopathy, restricted cardiomyopathy, and other secondary cardiomyopathy; 17. patients with malignancy; 18. patients combined with other organ diseases such as hematopoietic system, nervous system, endocrine system like thyroid, and combined with psychosis; 19. there is uncontrolled hypertension, systolic pressure is greater than 180mmhg and/or diastolic pressure is greater than 110mmhg; 20. heart rate ≥ 130 times/minute before randomization, or malignant ventricular arrhythmia affecting hemodynamic; 21. neuromuscular disease, disability or other non-cardiac causes influencing the performance of 6 minute walk test; 22. occurred within 3 months: acute coronary syndrome, stroke, transient cerebral ischemic attack; cardiac, carotid artery or other major vascular surgery; percutaneous coronary intervention (pci) or carotid artery angioplasty or coronary bypass surgery and other cardiac surgery; or scheduled for percutaneous intervention and surgery surgical treatment within 6 months; 23. has been implanted pacemaker/defibrillator (crt-p/d) of cardiac resynchronization therapy within 6 months, or the intention to implant a similar device within 6 months after randomization; 24. has been received major surgery within 6 months prior to randomization, or intend to receive major surgical treatment within 6 months; 25. history of heart transplantation or waiting for transplantation or using a left ventricular assist device (lvad) or a heart transplant intention (waiting for transplantation) or intend to use vad over the next 6 months; 26. nursing or pregnant women, or women of childbearing age without contraception, or patients planned pregnancy in 6 months; 27. history of major organ transplant (such as lung, liver, bone marrow, kidney) 28. patients have been involved or to be involved in other clinical trials within one month; 29. patients cannot understand the informed consent form or cannot make decisions or of poor compliance; 30. patients judged as unsuitable for the study and life expectancy less than 1 year by investigators.