Intravenous Iron in Patients With Severe Chronic Heart Failure and Chronic Kidney Disease
Recently, growing body of evidence support the finding that anemia frequently occurs in patients with chronic heart failure (CHF). Chronic kidney disease (CKD), as well, is highly prevalent among heart failure patients, and both anemia and CKD are independently associated with increased mortality. A vicious circle is established with CHF causing both chronic renal insufficiency and anemia, and CKD further aggravating anemia which, in turn, worsens CHF and so on. Treatment of the anemia breaks this circle and improves the quality of life, cardiac and renal functions in patients with severe CHF.
Intravenous iron alone was proved to allow the maintenance of target hematocrit in one-third of chronic renal failure predialysis patients.
Based on these considerations, intravenous iron for anemia in patients with CHF and moderate CKD would represent a reasonable therapeutic approach.
The aim of the trial is to assess the efficiency of intravenous iron therapy in the management of mild to moderate anemia associated with CHF NYHA III class and concomitant moderate CKD.
Chronic Kidney Disease
Chronic Heart Failure
Drug: iron sucrose
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Effects of Intravenous Iron Therapy for Anemia Correction in Patients With Severe Chronic Heart Failure and Concomitant Moderate Chronic Kidney Disease|
- percentage of patients with increased ejection fraction [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- the need for blood transfusions during the study period [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- serum ferritin level [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- transferrin saturation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- radial myocardial velocities [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- right ventricular function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- global diastolic function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- left ventricular mass index [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- major cardiovascular events (myocardial infarction, acute pulmonary edema, stroke) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- hospital admissions [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- death of the patient (all causes deaths, cardiac deaths) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- slope of GFR change [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- "death" of the kidney (initiation of renal replacement therapy) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Group I
iv iron sucrose
Drug: iron sucrose
Patients in Group I will receive iv iron sucrose, as described in the study protocol.
Patient in Group II will receive conventional treatment for chronic heart failure.
No Intervention: Group II
Patients will receive conventional treatment of Chronic Heart Failure.
Hide Detailed Description
Intravenous iron administration in CHF patients with absolute or functional iron deficiency could correct their anemia, thus improving cardiac function judged by ejection fraction and NYHA functional class. If true, enhancement of cardiac output will increase oxygen delivery to tissues, including renal cortex. This might improve the renal functions and slow the rate of progression of CKD reflected by the slope of decline in glomerular filtration rate (GFR).
Since erythropoietin synthesis is located in peritubular fibroblasts from outer renal cortex, which is the most affected area during chronic hypoxia, increasing renal blood flow after anemia correction is expected to restore optimal erythropoietin production and normalize plasma Epo levels.
The primary objective is to assess the efficiency of intravenous iron therapy in the management of mild to moderate anemia associated with chronic heart failure NYHA III class and concomitant moderate chronic kidney disease.
The secondary objectives are to determine if the correction of anemia in these patients affects the cardiac function, the rate of progression of CKD and the plasma erythropoietin levels.
The study will be conducted in accordance with the Declaration from Helsinki and Tokyo, with the amendments from Venice (1983), after the approval by the local ethics committee.
The total observation period will be of 28 weeks, with a pre-study phase (selection, randomization of subjects) 4 weeks.The study period will last 24 weeks, with a possible extension to 48 weeks, depending on the results of this first phase.
200 anemic patients with chronic heart failure class NYHA III and concomitant stage 3 chronic kidney disease will be enrolled, after obtaining their written informed consent.
All patients will be evaluated for the inclusion and exclusion criteria at enrollment and at each visit during the pre-study phase. Only patients fulfilling all the requested criteria at all evaluation moments will be enrolled. The enrolled subjects will be centrally randomly assigned in a 1:1 ratio into two study groups.
Group I (treatment group): Subjects assigned to this group will receive intravenous iron (ferric sucrose product Venofer® 2%, 5mL/ampoule) in a starting dose of 200mg (2 ampoules) diluted in 150mL 0.9% NaCl solution, over 60 minutes, once a week for the first four administrations, and then every other week until hemoglobin levels reach 12g/dL. Then, iron dose will be adjusted to 1 ampoule at 2-4 weeks interval, as needed to maintain these levels with serum ferritin ≤500ng/mL.
Iron administration will be discontinued if serum ferritin will exceed 500ng/mL, and will be restarted with a reduced dosage (1 ampoule at every 2-4 weeks) once serum ferritin decrease below this value.
Conventional treatment for CHF will be continued as needed. Group II (control group): Subjects assigned to this group will continue their conventional treatment for CHF as needed, without iron supplementation.
No other anti-anemic medication will be administered in either group during the study period.
Subject's visits will take place at two weeks intervals in the first 12 weeks of the study phase and at 4 weeks apart thereafter. At each visit will be recorded, according to the schedule, data concerning physical examination, including signs of CHF, hematological and iron status, renal function, concomitant medication and adverse events.
Parameters recorded at the time of first iron administration will serve as baseline determination.
The completion of the study will be declared when 200 subjects will complete the whole observation period, according to the above protocol.
|Contact: Gabriel Mircescu, Professor||+40 722 email@example.com|
|Contact: Liliana Garneata, MD, PhDfirstname.lastname@example.org|
|"Dr Carol Davila" Teaching Hospital of Nephrology||Recruiting|
|Bucharest, Romania, 010731|
|Contact: Liliana Garneata, Md, PhD +40722619358 email@example.com|
|Sub-Investigator: Ligia Petrescu, MD, PhD|
|Sub-Investigator: Simona Hildegard Stancu, MD, PhD|
|Sub-Investigator: Cristina Stela Capusa, MD, PhD|
|Principal Investigator: Gabriel Mircescu, Professor|
|Sub-Investigator: Liliana Garneata, MD, PhD|
|"Caritas" Teaching Hospital, Cardiology Department||Recruiting|
|Contact: Ondin Zaharia, MD, PhD firstname.lastname@example.org|
|Principal Investigator: Tiberiu Nanea, Professor|
|Sub-Investigator: Ondin Zaharia, MD, PhD|
|Study Director:||Gabriel Mircescu, Professor||Dr Carol Davila Teaching Hospital of Nephrology|
|Principal Investigator:||Tiberiu Nanea, Professor||"Caritas" Teaching Hospital, Bucharest|
|Principal Investigator:||Liliana Garneata, MD, PhD||"Dr Carol Davila" Teaching Hospital of Nephrology, Bucharest|