Clinical trial NCT04063033: IV Iron in Acute Decompensated Heart Failure
Official title: Randomized Bilnded Controlled Trial Comparing The Effect of IV Sodium Ferric Gluconate Complex (FERRLECIT R) on Outcome Patients Admitted Due To Acute Decompansated Heart Failure With Iron Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Lead sponsor: Rambam Health Care Campus
Sponsor class: OTHER
First posted: 2019-08-20
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomisation to two groups, One receiving IV Iron on top of standard therapy while admitted to the hospital and the other receiving only standard therapy for acute heart failure.
Primary purpose: TREATMENT

Brief summary: The study aims Compare the effect of addition of IV FERRLECITR (ferric gluconate) to standard therapy to standard therapy alone (without any IV iron treatment) in patients admitted with acute decompensated heart failure.

Detailed description: Heart Failure (HF) constitutes one of the biggest burdens on the public health system, with incidence of 20 per 1000 persons above the age of 65 and up to 80 per 1000 persons above 85 years of age. Acute decompensated heart failure (ADHF) is the most common cause of hospitalizations among patients above the age of 65. Even with the advances in the treatment and management of HF, the prognosis of these patients remains poor. HF results in impaired quality of life (QoL), repeated hospitalizations and poor life expectancy.

Iron deficiency (ID) is a common comorbidity in HF patients, and is associated with poor outcome, worsening of New York Heart Association (NYHA) Class, and re-hospitalizations. While the mechanisms and pathophysiology of ID in HF is not well understood, it is presumed to be a combination of impaired absorption, renal dysfunction, hemodilution and drugs that are used for the treatment of HF.

The advantages of (intra-venous) IV ferric carboxymaltose to patients with reduced ejection fraction (HFrEF) with stable chronic heart failure and functional ID has been shown to reduce the risk of hospitalizations up to 60%, improve symptoms, exercise tolerance, functional capacity and overall QoL . Accordingly, the latest 2016 ESC Guidelines recommended the treatment in patients with HfrEF with reduced ejection fraction (HFrEF) and ID (Class IIA,LOC A).

The two major, placebo-controlled studies, mentioned above (CONFIRM-AF and FAIR-AF) have demonstrated the positive outcomes after correction of ID in stable HF patients, with a well-tolerated IV substance. However, there is no data today concerning the role of IV iron repletion in patients with decompensated HF and preserved EF. Furthermore, previous studies excluded a substantial portion of the HFrEF population recently admitted with (acute decompensated heart failure) ADHF and diagnosed with ID.

The effect of treating iron deficiency on quality of life an functional status has already been studied and found useful with various types of intravenous iron in the chronic kidney disease and inflammatory bowel disease.

In this study we aim to examine the effect of IV iron (ferric gluconate) which is a more affordable IV Iron on patients admitted due to acute heart failure with minimal exclusion criterias.

Eligibility criteria: Inclusion Criteria:

1. Patients admitted due to acute decompensated heart failure to internal medicine department H or cardiology department.

   * Must meet two of the following criteria :

     * NT pro BNP \> 300 pg/ml (\>800 pg/ml in the presence of Atrial Fibrillation).
     * Peripheral pitting edema,
     * Jugular Venous Distention,
     * pulmonary edema/congestion according to physical examination or Chest X-ray.
   * IV furosemide treatment on admission to ER or internal ward/cardiology department.
2. Hb level 8-14 mg/dl on admission.
3. Iron stores: Ferritin \<100 or Ferritin 100-300 and Transferrin saturation \< 20%.
4. No evidence of active bleeding.
5. Patient provided informed consent.

Exclusion Criteria:

1. Cardiogenic shock or any other condition requiring IV vasopressors.
2. Previous allergy or anaphylaxis due to IV Iron.
3. Active malignancy undergoing treatment.
4. Status post major surgery involving substantial blood loss in the past 3 months.
5. Indication for Blood transfusion.
6. Infection indicating IV antibiotics.
7. History of acquired iron overload; known haemochromatosis or first relatives with hemochromatosis; and allergic disorders (asthma, eczema, and anaphylactic reactions).
8. hemolytic anemia.
9. History of chronic liver disease and/or alanine transaminase (ALT) or aspartate transaminase (AST) \>3 times the upper limit of the normal range; chronic lung disease; myelodysplastic disorder; and known HIV/AIDS disease.
10. Recipient of immunosuppressive therapy or renal dialysis. History of erythropoietin, IV iron therapy, and blood transfusion in previous 30 days.
11. Unstable angina pectoris, as judged by the investigator; severe uncorrected valvular disease or left ventricular outflow obstruction; obstructive cardiomyopathy; uncontrolled fast atrial fibrillation or flutter (heart rate \>110 beats per minute \[bpm\]); uncontrolled symptomatic brady- or tachyarrhythmias.
12. Musculoskeletal limitation that, in the judgement of the investigator, would impair cardiopulmonary exercise testing.
13. Pregnant or breastfeeding.
14. Inability to comprehend study protocol.
15. Parallel participation in another clinical trial.

Primary outcomes:
measure: Functional Capacity
timeFrame: 12 and 24 Weeks
Secondary outcomes:
measure: Change in NYHA
timeFrame: 12 and 24 weeks
measure: All cause mortality
timeFrame: 1 Year
measure: Hospitalizations due to heart failure.
timeFrame: 1 year
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Medical Center
Study officials:
affiliation: Rambam Health Care Campus
name: Erez Marcusohn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marcusohn E, Borreda I, Hellman Y, Habib M, Bahouth F, Epstein D, Zukermann R. IV Sodium Ferric Gluconate Complex in Patients With Iron Deficiency Hospitalized due to Acute Heart Failure-Investigator Initiated, Randomized Controlled Trial. J Cardiovasc Pharmacol. 2022 Aug 1;80(2):194-196. doi: 10.1097/FJC.0000000000001287.