Evaluating Iron Protein Succinylate Oral Solution in Treating Chronic Heart Failure and Iron Deficiency

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

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.

Study Overview

• Status: Unknown
• Conditions: Iron-deficiency; Chronic Heart Failure
• Intervention / Treatment: Drug: Iron protein succinylate oral solution; Other: standard treatment

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.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: standard treatment + Iron succinylate; 1 bottle orally, twice daily, take orally before meals	Drug: Iron protein succinylate oral solution; Iron protein succinylate oral solution; Other: standard treatment; standard treatment
Placebo Comparator: standard treatment + placebo; 1 bottle orally, twice daily, take orally before meals	Other: standard treatment; standard treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of 6 Minute walk distances	The change of 6 Minute walk distances compared to baseline after patients receiving 24 week treatment.	24 week

Secondary Outcome Measures

Outcome Measure	Time Frame
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 6 Minute walk distance after patients receiving 16 week treatment	16 week
Change of blood NT-proBNP after patients receiving 24 week treatment	24 week
Cardiovascular death or heart failure re-hospitalization 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

Other Outcome Measures

Outcome Measure	Time Frame
Index change in hemoglobin, serum iron, ferritin and transferrin saturation, and the like patients receiving 24 week treatment	24 week
Index change in left ventricular ejection fraction, left atrial diameter, left ventricular diameter, pulmonary artery pressure and diastolic function after patients receiving 24 week treatment	24 week
Rehospitalization with heart failure after patients receiving 24 week treatment	24 week
Heart failure mortality after patients receiving 24 week treatment	24 week
Cardiovascular readmission rates after patients receiving 24 week treatment	24 week
Cardiovascular mortality after patients receiving 24 week treatment	24 week
Comprehensive due readmission rates after patients receiving 24 week treatment	24 week
Comprehensive cause mortality after patients receiving 24 week treatment	24 week
C Reactive protein level after patients receiving 24 week treatment	24 week

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 13, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Anemia, Iron-Deficiency; Hematinics; Iron protein succinylate
• Other Study ID Numbers: 2016-ZX02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No