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

NCT ID: NCT02392910

Last Updated: 2015-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2012-02-29

Brief Summary

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.

Detailed 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).

Conditions

Iron Deficiency; Heart Failure; Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group A

Placebo

Group Type: OTHER

Placebo

Intervention Type: DRUG

At each visit, the patient lay on a stretcher and underwent a vein cannulation in the forearm with a commercial canula no. 16, which was connected to IV tubing that was connected to a bag of isotonic saline solution 0.9% (200 ml). Each infusion was administered throughout 60 min. This scheme was followed for 5 consecutive weeks.

Group B

Iron Sucrose

Group Type: OTHER

Iron Sucrose

Intervention Type: DRUG

At each visit, the patient lay on a stretcher and underwent a vein cannulation in the forearm with a commercial canula no. 16, which was connected to IV tubing that was connected to a bag contained 200 ml isotonic saline solution 0.9% plus 200 mg of Iron Sucrose. Each infusion was administered throughout 60 min. This scheme was followed for 5 consecutive weeks.

Interventions

Iron Sucrose

At each visit, the patient lay on a stretcher and underwent a vein cannulation in the forearm with a commercial canula no. 16, which was connected to IV tubing that was connected to a bag contained 200 ml isotonic saline solution 0.9% plus 200 mg of Iron Sucrose. Each infusion was administered throughout 60 min. This scheme was followed for 5 consecutive weeks.

Intervention Type: DRUG

Placebo

At each visit, the patient lay on a stretcher and underwent a vein cannulation in the forearm with a commercial canula no. 16, which was connected to IV tubing that was connected to a bag of isotonic saline solution 0.9% (200 ml). Each infusion was administered throughout 60 min. This scheme was followed for 5 consecutive weeks.

Intervention Type: DRUG

Other Intervention Names

Venofer; Sodium Chloride 0.9%

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Aleman

OTHER

Sponsor Role: lead

Responsible Party

Jorge Eduardo Toblli

Jorge Eduardo Toblli, MD; PhD; FASN. Professor of Medicine. Chief of Nephrology.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jorge E Toblli, MD; PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Aleman

Locations

Hospital Aleman

Buenos Aires, Buenos Aires F.D., Argentina

Countries

Argentina

References

Toblli JE, Lombrana A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007 Oct 23;50(17):1657-65. doi: 10.1016/j.jacc.2007.07.029.

Reference Type: BACKGROUND

PMID: 17950147 (View on PubMed)

Other Identifiers

5427-06/07

Identifier Type: -

Identifier Source: org_study_id