Clinical trial NCT02698046: Oral Iron Therapy in Chronic Heart Failure Patients
Official title: Oral Iron Therapy in Chronic Heart Failure Patients: a Randomized, Placebo-controlled and Double-blind Clinical Trial (Pilot Study) of Efficiency
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Failure
Keywords: Heart failure
Iron
Anemia
Chronic disease
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2016-03-03
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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).

Primary outcomes:
measure: Biochemical parameter of serum transferrin saturation
timeFrame: 4 months
Secondary outcomes:
measure: Biochemical parameter of hemoglobin in the hemogram analysis
timeFrame: 4 months
measure: Biochemical parameter of serum ferritin
timeFrame: 4 months
measure: Volume of oxygen consumed at peak exercise during cardiopulmonary exercise testing
timeFrame: 4 months
measure: Volume of oxygen consumed at anaerobic threshold during cardiopulmonary exercise testing
timeFrame: 4 months
measure: Ejection fraction of the left ventricle on doppler echocardiographic study
timeFrame: 4 months
measure: Biochemical parameter of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) serum levels
timeFrame: 4 months
measure: Blood pressure results during mechanoreflex evaluation
timeFrame: 4 months
measure: Heart rate results during mechanoreflex evaluation
timeFrame: 4 months
measure: Volume of oxygen consumed results during mechanoreflex evaluation
timeFrame: 4 months
measure: Total score of physical, emotional, and overall dimensions domains of the Minnesota Living with Heart Failure Questionnaire
timeFrame: 4 months
Other outcomes:
measure: Biochemical parameter of serum urea
timeFrame: 4 months
measure: Biochemical parameter of serum creatinine
timeFrame: 4 months
measure: Biochemical parameter of serum sodium
timeFrame: 4 months
measure: Biochemical parameter of serum potassium
timeFrame: 4 months
Locations:
city: Ribeirao Preto
country: Brazil
facility: Division of Cardiology, Department of Internal Medicine
state: Sao Paulo
Study officials:
affiliation: University of Sao Paulo
name: Jaqueline RS Gentil, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.