Oral Iron Therapy in Chronic Heart Failure Patients

• ClinicalTrials.gov Identifier: NCT02698046
• Recruitment Status: Unknown
• First Posted: March 3, 2016
• Last Update Posted: March 3, 2016
• Sponsor: University of Sao Paulo
• Collaborator: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Information provided by (Responsible Party): Jaqueline Rodrigues de Souza Gentil, University of Sao Paulo

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Heart Failure	Dietary Supplement: Ferrous sulfate; Dietary Supplement: Placebo starch	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Oral Iron Therapy in Chronic Heart Failure Patients: a Randomized, Placebo-controlled and Double-blind Clinical Trial (Pilot Study) of Efficiency
• Study Start Date: August 2015
• Estimated Primary Completion Date: June 2016
• Estimated Study Completion Date: October 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Biochemical parameter of serum transferrin saturation [ Time Frame: 4 months ]

Secondary Outcome Measures :

1. Biochemical parameter of hemoglobin in the hemogram analysis [ Time Frame: 4 months ]
2. Biochemical parameter of serum ferritin [ Time Frame: 4 months ]
3. Volume of oxygen consumed at peak exercise during cardiopulmonary exercise testing [ Time Frame: 4 months ]
   Unit of measure mL/kg/min
4. Volume of oxygen consumed at anaerobic threshold during cardiopulmonary exercise testing [ Time Frame: 4 months ]
   Unit of measure mL/kg/min
5. Ejection fraction of the left ventricle on doppler echocardiographic study [ Time Frame: 4 months ]
   Unit of measure %
6. Biochemical parameter of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) serum levels [ Time Frame: 4 months ]
7. Blood pressure results during mechanoreflex evaluation [ Time Frame: 4 months ]
   Unit of measure mmHg
8. Heart rate results during mechanoreflex evaluation [ Time Frame: 4 months ]
   Unit of measure beats per minute
9. Volume of oxygen consumed results during mechanoreflex evaluation [ Time Frame: 4 months ]
   Unit of measure mL/kg/min
10. Total score of physical, emotional, and overall dimensions domains of the Minnesota Living with Heart Failure Questionnaire [ Time Frame: 4 months ]
    Score range 0 to 105 points

Other Outcome Measures:

1. Biochemical parameter of serum urea [ Time Frame: 4 months ]
   Unit of measure mg/dL
2. Biochemical parameter of serum creatinine [ Time Frame: 4 months ]
   Unit of measure mg/dL
3. Biochemical parameter of serum sodium [ Time Frame: 4 months ]
   Unit of measure mg/dL
4. Biochemical parameter of serum potassium [ Time Frame: 4 months ]
   Unit of measure mg/dL

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Jaqueline RS Gentil, Master; +551633154577; jaqueline.gentil@gmail.com

Locations

Brazil

Division of Cardiology, Department of Internal Medicine; Recruiting

Ribeirao Preto, Sao Paulo, Brazil, 14000-000

Contact: Jaqueline RS Gentil, Master +551633154577 jaqueline.gentil@usp.br

Contact: Marcus V Simoes, PhD +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

Sponsors and Collaborators

University of Sao Paulo

Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

• Principal Investigator: Jaqueline RS Gentil, Master; University of Sao Paulo

More Information

Publications:

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.

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.

• Responsible Party: Jaqueline Rodrigues de Souza Gentil, Master degree, University of Sao Paulo
• ClinicalTrials.gov Identifier: NCT02698046
• Other Study ID Numbers: 13/03301-1
• First Posted: March 3, 2016
• Last Update Posted: March 3, 2016
• Last Verified: February 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Jaqueline Rodrigues de Souza Gentil, University of Sao Paulo:

Heart failure; Iron; Anemia; Chronic disease

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases