IV Sodium Ferric Gluconate Complex in Patients Undergoing TAVI

Randomized Bilnded Controlled Trial Comparing The Effect of IV Sodium Ferric Gluconate Complex (FERRLECIT R) on Outcome of Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)

Iron deficiency is common among patients undergoing TAVI. It is estimated at 54-79%. Previous non-randomized small trial have shown symptomatic benefit in treating iron deficiency in this group of patients.

The investigators predict, that as IV iron will improve symptoms, quality of life and exercise tolerance in this group of patients.

Study Overview

• Status: Recruiting
• Conditions: Aortic Stenosis; Iron Deficiency Anemia Due to Blood Loss
• Intervention / Treatment: Drug: IV Sodium Ferric Gluconate Complex

Detailed Description

Iron deficiency (ID) among patients undergoing transcatheter aortic valve implantation (TAVI) is common (54%-79% .These patients suffer from higher mortality, unplanned readmission for worsening heart failure or red blood cell transfusions during the first year after TAVI.IV Iron therapy was found to be feasible in the 56 patients who were treated and showed improvement in symptoms at 30 days follow-up.Anemia in TAVI patients is multifactorial, related to advanced age, frailty, coagulopathy, medications, kidney disease, bleeding, inflammation and ID. The most treatable part is ID.

Iron deficiency (ID) is a common comorbidity in other diseases. In heart failure (HF) patients, it 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). No guidelines recommend IV iron supplementation in TAVI patients.

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. Furthermore, the effect of treating iron deficiency on quality of life and functional status has already been studied and found useful with various types of intravenous iron in the chronic kidney disease and inflammatory bowel disease.The effect of treating with oral iron supplements has been studied in HF patients with no difference in exercise capacity, symptoms, NT pro BNP, iron stores, Hemoglobin levels or V02 compared to placebo.

In this study the investigators aim to examine the effect of IV iron (ferric gluconate) which is a more affordable IV Iron on patients with ID admitted for TAVI. No randomized trial has been published in this topic to this day.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Erez Marcusohn, MD; Phone Number: 97247772180; Email: e_marcusohn@rambam.health.gov.il

Study Locations

• Israel
  • Haifa, Israel
    • Recruiting
    • Rambam Medical Center
    • Contact: Erez Marcusohn, MD; Phone Number: 972503482952; Email: e_marcusohn@rambam.health.gov.il
    • Contact: Robert Zukerman, MD; Phone Number: 972545401254; Email: r_zukerman@rambam.health.gov.il

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: (All criteria need to be met)

  1. Patients admitted for TAVI.
  2. Hb level 8-14 mg/dl on admission.
  3. No evidence of active bleeding.
  4. Patient provided informed consent.
  5. The patient is able to walk without support for 6 minutes.
  6. LVEF >= 45%

• Exclusion criteria:

  1. Previous allergy or anaphylaxis due to IV Iron.
  2. Active malignancy undergoing treatment.
  3. Status post major surgery involving substantial blood loss in the past 3 months.
  4. Infection indicating IV antibiotics, not including prophylaxis for TAVI.
  5. History of acquired iron overload; known haemochromatosis or first relatives with hemochromatosis; and allergic disorders (asthma, eczema, and anaphylactic reactions).
  6. Hemolytic anemia.
  7. 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.
  8. Recipient of immunosuppressive therapy or renal dialysis. History of erythropoietin, IV iron therapy, and blood transfusion in previous 30 days.
  9. Musculoskeletal limitation that, in the judgement of the investigator, would impair 6-minute walk.
  10. Pregnant or breastfeeding.
  11. Inability to comprehend study protocol.
  12. Parallel participation in another clinical trial.
  13. During TAVI or the day following the procedure:

I. Major complication of death. II. Cardiogenic shock or any other condition requiring IV vasopressors. III. Major bleeding according to BARC 2 criteria or above. IV. Need for more than 2 pack cells during or after the procedure.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment; 100 patients receiving IV Iron during index hospitalisation.	Drug: IV Sodium Ferric Gluconate Complex; 125 mg of IV Iron per day to 3 to 5 days according to hospitalisation length.; Other Names: IV Ferrlecit
No Intervention: No treatment; 100 patients not receiving IV Iron above standout treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute walk change at 1 month.	6-minute walk change (meters) between baseline and 1 month follow-up.	30 days.
6-minute walk change at one year.	6-minute walk change (meters) between baseline and 1 year follow-up.	One year.

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Investigators: Principal Investigator: Erez Marcusohn, MD, Cardiology Department, Rambam Health Care Campus,Haifa,Israel

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2020
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 12, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Anemia, Iron-Deficiency; Aortic Valve Stenosis; Hematinics; Ferric gluconate
• Other Study ID Numbers: 0438-20 RMB

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No