Oral Iron Therapy in Chronic Heart Failure Patients

Heart Failure Clinical Trial

Official title:

Oral Iron Therapy in Chronic Heart Failure Patients: a Randomized, Placebo-controlled and Double-blind Clinical Trial (Pilot Study) of Efficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02698046
• Other study ID #: 13/03301-1
• Status: Recruiting
• Phase: Phase 3
• First received: December 16, 2015
• Last updated: February 28, 2016
• Start date: August 2015
• Est. completion date: October 2016

Study information

• Verified date: February 2016
• Source: University of Sao Paulo
• Contact: Jaqueline RS Gentil, Master
• Phone: +551633154577
• Email: jaqueline.gentil[@]gmail.com
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study is design to evaluate the effectiveness of oral iron therapy in patients with heart failure and identify the central and peripheral mechanisms involved in the improvement of functional capacity after intervention. The investigation includes subjective and objective measures on exercise performance and heart function after intervention, and the tolerability of oral iron treatment.

Description:

This is a placebo-controlled, double-blind and randomized clinical trial that will include patients with symptomatic stable chronic heart failure (New York Heart Association Functional Class II or III), with diagnosis of iron deficiency (ferritin <100 ng / dL or ferritin between 100 - 300 ng / dL and transferrin saturation <20%) followed in an outpatient clinic. The enrolled patients (n = 36) will be randomly allocated in the ratio 2:1 to treatment with 60 mg of elemental iron orally (n = 24) or placebo administration (n = 12), 3 times daily for 4 months. The primary outcome investigated will be an increase of the transferrin saturation ≥ 10 percentage points between baseline and after the intervention. Secondary outcomes of the study will be the change in iron stores, red blood cell indices, neurohumoral activation, left ventricular systolic function, functional capacity, mechanoreflex activity, and quality life score.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: October 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Both gender patients aged over 18 years;

• Diagnosis of chronic heart failure (identified by the use of Framingham criteria) for = 6 months;

• New York Heart Association functional class II and III;

• Left ventricular ejection fraction = 45%

• Regular attendance in an outpatient Heart Failure Clinic;

• Adequate therapeutic drug for heart failure syndrome based on beta-adrenergic blocker, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and mineralocorticoid receptor blocker;

• Evidence of iron deficiency in biochemical analyses: ferritin values < 100 ng/dL or between 100 ng/dL and 300 ng/dL, with transferrin saturation < 20%;

• Hemoglobin value between 9,0 - 16 g/dL;

• Provide written informed consent.

Exclusion criteria

• Recent device implant (in the last 3 months) or perspective of device implantation (conventional or multisite pacing) in the next 6 months;

• Known active infection, inflammatory disease or C-reactive protein > 20 mg/dL

• Immunosuppressive therapy;

• In use of erythropoietin and/or current treatment with oral or intravenous iron;

• Clinically bleeding or blood transfusion in previous 3 months;

• Renal failure on dialysis;

• Hemoglobinopathies, hemochromatosis or active malignancy;

• Unstable angina pectoris or clinically significant uncorrected valvular disease, except mitral and tricuspid regurgitation secondary to ventricular dilatation;

• Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack within the last 3 months;

• Uncontrolled arterial hypertension;

• Evidence of comorbidity that features active systemic disease, i.e. liver disease, collagen disease and untreated hyperthyroidism or hypothyroidism;

• Pregnant or lactating women;

• Anaemia due to reasons other than iron de?ciency (i.e. vitamin B12 deficiency);

• Recent admission for decompensated heart failure (last 3 months).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure

Intervention

Dietary Supplement:
• Ferrous sulfate
200mg of ferrous sulfate three times a day for 4 months
• Placebo starch
200mg of placebo starch three times a day for 4 months

Locations

Country	Name	City	State
Brazil	Division of Cardiology, Department of Internal Medicine	Ribeirao Preto	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009 Dec 17;361(25):2436-48. doi: 10.1056/NEJMoa0908355. Epub 2009 Nov 17. — View Citation

Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010 Aug;31(15):1872-80. doi: 10.1093/eurheartj/ehq158. Epub 2010 Jun 21. Erratum in: Eur Heart J. 2011 May;32(9):1054. — View Citation

Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol. 2011 Sep 13;58(12):1241-51. doi: 10.1016/j.jacc.2011.04.040. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biochemical parameter of serum urea	Unit of measure mg/dL	4 months	Yes
Other	Biochemical parameter of serum creatinine	Unit of measure mg/dL	4 months	Yes
Other	Biochemical parameter of serum sodium	Unit of measure mg/dL	4 months	Yes
Other	Biochemical parameter of serum potassium	Unit of measure mg/dL	4 months	Yes
Primary	Biochemical parameter of serum transferrin saturation		4 months	No
Secondary	Biochemical parameter of hemoglobin in the hemogram analysis		4 months	No
Secondary	Biochemical parameter of serum ferritin		4 months	No
Secondary	Volume of oxygen consumed at peak exercise during cardiopulmonary exercise testing	Unit of measure mL/kg/min	4 months	No
Secondary	Volume of oxygen consumed at anaerobic threshold during cardiopulmonary exercise testing	Unit of measure mL/kg/min	4 months	No
Secondary	Ejection fraction of the left ventricle on doppler echocardiographic study	Unit of measure %	4 months	No
Secondary	Biochemical parameter of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) serum levels		4 months	No
Secondary	Blood pressure results during mechanoreflex evaluation	Unit of measure mmHg	4 months	No
Secondary	Heart rate results during mechanoreflex evaluation	Unit of measure beats per minute	4 months	No
Secondary	Volume of oxygen consumed results during mechanoreflex evaluation	Unit of measure mL/kg/min	4 months	No
Secondary	Total score of physical, emotional, and overall dimensions domains of the Minnesota Living with Heart Failure Questionnaire	Score range 0 to 105 points	4 months	No