Hospitalization & Mortality in Patients With Iron Deficiency CKD and HF Treated With i.v. Iron.

Hospital Aleman

Status and phase: Completed; Phase 4

Conditions: Chronic Kidney Disease; Iron Deficiency; Heart Failure

Treatments: Drug: Placebo; Drug: Iron Sucrose

Study type: Interventional

Funder types: Other

Identifiers

NCT02392910

5427-06/07

Details and patient eligibility

About

Iron deficiency, independent of anemia, appears to increase morbidity and mortality as well as impairing health-related quality of life in chronic heart failure (CHF), and these effects are compounded when patients also experience chronic kidney disease (CKD). This study was designed to determine the effects of intravenous iron treatment on morbidity and mortality following an initial 6-month period and a longer period of up to 5 years.

Full description

Effect of i.v. iron sucrose on iron parameters and anemia

• During the original 6 month trial, patients in the i.v. iron group received 1000mg iron per the protocol. No patients required iron in the subsequent 6 months.
• During the subsequent follow-up, patients required a mean of between 165 and 274 mg iron per year (range: 0 to 600 mg per patient per year).
• Post the initial 1000mg iron, 19 out of 20 patients required at least a second dose of i.v. iron. Most patients required only one or two doses per year.
• The average time to requiring a second iron administration was 14.5 ± 2.7 months (range: 14 months, 23 months).
• Correction of iron deficiency (ID) resulted in statistically significant increases in transferrin saturation (TSAT) throughout the study (p < 0.01 untreated group). At all measured points, TSAT values in the treated group were at least on target (> 20% increase).
• For serum ferritin, significant differences were observed at 6 months and 1 year however this difference was not observed at 5 years post baseline where serum ferritin values were 173ng/mL and 167ng/mL for the control and IV iron groups, respectively.
• Statistically significant improvements versus the untreated group were observed for both hemoglobin (Hb) and creatinine clearance (CrCl) as well as for left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class at each year.

Effect of i.v. iron sucrose on hospitalizations and mortality

• There were numerically fewer hospitalization reported at 6 months compared to those among untreated patients (0% and 25%, respectively), although the difference versus untreated patients was not statistically significant (p=ns).
• At 1 year after commencing the original study, the number of patients requiring a hospitalization (for any reason) was 50% in the control group and 10% in the IV iron group (p<0.01).
• By 5 years follow-up these rates had increased to 85% in the control arm and 20% in the IV iron treated group (p<0.01).
• In relation to all-cause mortality, there were no deaths in either group after the first 6 months. The number of deaths due to any cause after year 1 had increased in both groups (20% in the untreated group, 5% in the treated group; p=ns).
• At 5 years follow-up, 11 (55%) of patients in the control arm were deceased, compared with 4 (20%) in the IV iron treated group (p < 0.05).

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

• LV ejection fraction (EF) ≤ 35%
• New York Heart Association (NYHA) functional class II to IV
• Anemia with an iron deficit defined by Hb 12.5 g/dl for men and 11.5 g/dl for women, and some of the following: serum ferritin 100 ng/ml and/or with transferrin saturation (TSAT) 20%
• Creatinine clearance 90 ml/min.

Exclusion:

• Hemodialysis therapy
• Anemia not due to iron deficiency
• NYHA functional class I
• History of allergy to the iron supplements
• Acute bacterial infections, parasitism known in the 4 previous weeks
• Neoplasm
• Chronic digestive diseases
• Hypothyroidism
• Congenital cardiopathies
• Receiving iron supplements in the 4 previous weeks
• Receiving rhEPO in the 4 previous weeks
• History of hospitalization during the 4 weeks before enrollment into the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 2 patient groups

Group A

Other group

Description:

Placebo

Treatment:

Drug: Placebo

Group B

Other group

Description:

Iron Sucrose

Treatment:

Drug: Iron Sucrose