Oral Iron Therapy in Chronic Heart Failure Patients

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

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure
• Intervention / Treatment: Dietary supplement: Ferrous sulfate; Dietary supplement: Placebo starch

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jaqueline RS Gentil, Master; Phone Number: +551633154577; Email: jaqueline.gentil@gmail.com

Study Locations

• Brazil
  • Sao Paulo
    • Ribeirao Preto, Sao Paulo, Brazil, 14000-000
      • Recruiting
      • Division of Cardiology, Department of Internal Medicine
      • Contact: Jaqueline RS Gentil, Master; Phone Number: +551633154577; Email: jaqueline.gentil@usp.br
      • Contact: Marcus V Simoes, PhD; Phone Number: +551636022791
      • Sub-Investigator: Marcus Vinícius Simões, PhD
      • Sub-Investigator: Pedro V Schwartzmann, PhD
      • Sub-Investigator: Eduardo EV Carvalho, Master
      • Sub-Investigator: Luciana P Seabra, Master
      • Sub-Investigator: Júlio C Crescêncio, PhD
      • Sub-Investigator: Lourenço Gallo Junior, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 deficiency (i.e. vitamin B12 deficiency);
• Recent admission for decompensated heart failure (last 3 months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo starch; 200mg of placebo starch three times a day for 4 months
Experimental: Ferrous sulfate	Dietary supplement: Ferrous sulfate; 200mg of ferrous sulfate three times a day for 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Biochemical parameter of serum transferrin saturation	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical parameter of hemoglobin in the hemogram analysis		4 months
Biochemical parameter of serum ferritin		4 months
Volume of oxygen consumed at peak exercise during cardiopulmonary exercise testing	Unit of measure mL/kg/min	4 months
Volume of oxygen consumed at anaerobic threshold during cardiopulmonary exercise testing	Unit of measure mL/kg/min	4 months
Ejection fraction of the left ventricle on doppler echocardiographic study	Unit of measure %	4 months
Biochemical parameter of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) serum levels		4 months
Blood pressure results during mechanoreflex evaluation	Unit of measure mmHg	4 months
Heart rate results during mechanoreflex evaluation	Unit of measure beats per minute	4 months
Volume of oxygen consumed results during mechanoreflex evaluation	Unit of measure mL/kg/min	4 months
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical parameter of serum urea	Unit of measure mg/dL	4 months
Biochemical parameter of serum creatinine	Unit of measure mg/dL	4 months
Biochemical parameter of serum sodium	Unit of measure mg/dL	4 months
Biochemical parameter of serum potassium	Unit of measure mg/dL	4 months

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Jaqueline RS Gentil, Master, University of Sao Paulo

Publications and helpful links

General Publications

• Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): June 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: December 16, 2015
• First Submitted That Met QC Criteria: February 28, 2016
• First Posted (Estimate): March 3, 2016

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: February 28, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Heart failure; Anemia; Iron; Chronic disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 13/03301-1

Plan for Individual participant data (IPD)

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