A Randomized, Double-blind, Multi-center Clinical Trial Prospectively Evaluating Iron Protein Succinylate Oral Solution in Treating Patients With Chronic Heart Failure and Iron Deficiency
Overview
- Phase
- Phase 4
- Intervention
- Iron protein succinylate oral solution
- Conditions
- Chronic Heart Failure
- Sponsor
- Lee's Pharmaceutical Limited
- Enrollment
- 600
- Primary Endpoint
- The change of 6 Minute walk distances
- Last Updated
- 8 years ago
Overview
Brief 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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Sign informed consent form;
- •Between 18 to 80 years old, male or female;
- •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;
- •LVEF\< 40% (determined by Simpson method) (valid for one week before randomization);
- •NYHA heart function II-III Grade;
- •NT-proBNP\>400pg/ml, it should be .900pg/ml at atrial fibrillation;
- •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%);
- •Capable of 6 Minute walk test.
Exclusion Criteria
- •Patients with significant bleeding: gastrointestinal bleeding, menorrhagia, history of gastrointestinal bleeding and no evidence of gastrointestinal disease healing;
- •History of oral iron supplementation and intolerance;
- •History of acquired iron overload;
- •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;
- •Patients in urgent need of blood transfusion;
- •VtaminB12 and/or folate deficiency, unless correctable; and Non-iron deficiency anemia;
- •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;
- •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);
- •Intestinal diseases which affect iron absorption such as inflammatory bowel disease and chronic pancreatitis;
- •Active infection;
Arms & Interventions
standard treatment + Iron succinylate
1 bottle orally, twice daily, take orally before meals
Intervention: Iron protein succinylate oral solution
standard treatment + Iron succinylate
1 bottle orally, twice daily, take orally before meals
Intervention: standard treatment
standard treatment + placebo
1 bottle orally, twice daily, take orally before meals
Intervention: standard treatment
Outcomes
Primary Outcomes
The change of 6 Minute walk distances
Time Frame: 24 week
The change of 6 Minute walk distances compared to baseline after patients receiving 24 week treatment.
Secondary Outcomes
- Cardiovascular death or heart failure re-hospitalization after patients receiving 24 week treatment(24 week)
- Change of 6 Minute walk distance after patients receiving 16 week treatment(16 week)
- Variety of overall status score（PGA）after patients receiving 24 week treatment(24 week)
- Kansas City Cardiomyopathy Questionnaire (KCCQ) rating change after patients receiving 24 week treatment(24 week)
- Change of blood NT-proBNP after patients receiving 24 week treatment(24 week)
- Comprehensive cause mortality after patients receiving 52 week treatment(24 week)
- EQ-5D Questionnaire score after patients receiving 24 week treatment(24 week)
- Change of NYHA grading after patients receiving 24 weeks treatment(24 week)