Chronic Kidney DiseasePhase 3NCT00384657
Intravenous Iron in Patients With Severe Chronic Heart Failure and Chronic Kidney Disease
A Phase 3 study testing iron sucrose in people with Chronic Kidney Disease and Chronic Heart Failure, run by Anemia Working Group Romania at 2 sites in Romania.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease, Chronic Heart Failure, Anemia
- What is being tested?
- iron sucrose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesRomania
- Study dates
- Jan 2008to Dec 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- persistent severe CHF: functional class NYHA III (marked limitation of physical activity - comfortable at rest, but less than ordinary activity results in shortness of breath and/or fatigue16); left ventricular ejection fraction (echocardiography) less than 40%; functional and systolic dysfunction criteria must be stable at two different examinations one month apart;
- stable stage 3 chronic kidney disease: estimated GFR between 30-59mL/min/1.73m2 (mean value of three measurements within the last 8 weeks, separated from each other by at least one week); stable renal function (at least three different measurements within the past 8 weeks, separated from each other by at least one week; the difference between the highest and the lowest value should be less than 5mL/min/1.73m2)
- mild to moderate anemia: hemoglobin levels < 12g/dL (mean value of three measurements within the last 8 weeks, separated from each other by at least one week) and stable (at least three measurements within the last 8 weeks; the difference between the highest and the lowest value should be less than 1.5g/dL);
- iron deficiency: absolute (serum ferritin < 100ng/mL) or functional (serum ferritin 100-300ng/mL and transferrin saturation < 20%)
Who cannot join
- evidence of active gastrointestinal or genital tract bleeding
- folate or vitamin B12 deficiency
- hypothyroidism
- hemolytic anemia
- any primary kidney diseases (glomerulonephritis, interstitial nephritis, cystic diseases)
- systemic diseases with renal involvement (lupus erythematosus, vasculitis, amyloidosis)
Show all 30Show fewer
- renal artery stenosis (>70% lumen reduction)
- diabetic nephropathy
- severe malnutrition (SGA score C or lower)
- active liver diseases
- infectious conditions
- malignancies
- C-reactive protein > 12 mg/L
- severe anemia (< 8.5g/dL)
- blood transfusions in the preceding two months
- iron therapy in the preceding three months
- concomitant erythropoietin therapy
- severe arterial hypertension (systolic BP >190 mm Hg and/or diastolic BP >115 mm Hg)
- recent history (less than 3 months) of acute coronary syndrome
- recent (less than 1 month) PCI
- recent (less than 1 month) CABG surgery
- active myocarditis
- active endocarditis
- more than mild valvar stenosis
- more than moderate valvar (mitral or aortic) regurgitation
- uncontrolled haemodynamically relevant atrial fibrillation/flutter
- hypertrophic cardiomyopathy
- acute and/or chronic pericarditis
- cor pulmonale
- participation in another study
Trial locations and contacts
2 sites in 1 country.
Romania2 sites
"Dr Carol Davila" Teaching Hospital of Nephrology
Bucharest, 010731
"Caritas" Teaching Hospital, Cardiology Department
Bucharest
About this study
Official title: The Effects of Intravenous Iron Therapy for Anemia Correction in Patients With Severe Chronic Heart Failure and Concomitant Moderate 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.
Read more
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.
Read the 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.
- Conditions
- Chronic Kidney Disease, Chronic Heart Failure, Anemia
- Being tested
- iron sucrose
- Keywords
- chronic heart failure, chronic kidney disease, anemia, intravenous iron
- Medical subject headings
- Renal Insufficiency, Chronic, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iron sucroseDrug
Also called Group I - iv iron group, Group II - conventional treatment group
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.
| Study group | Role | What they receive |
|---|---|---|
| Group I | Experimental | iv iron sucrose Receives: Drug: iron sucrose |
| Group II | No intervention | Patients will receive conventional treatment of Chronic Heart Failure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
percentage of patients with increased ejection fraction
Measured: 12 months
Secondary outcomes (12)
the need for blood transfusions during the study period
Measured: 12 months
serum ferritin level
Measured: 12 months
transferrin saturation
Measured: 12 months
radial myocardial velocities
Measured: 12 months
right ventricular function
Measured: 12 months
global diastolic function
Measured: 12 months
left ventricular mass index
Measured: 12 months
major cardiovascular events (myocardial infarction, acute pulmonary edema, stroke)
Measured: 12 months
hospital admissions
Measured: 12 months
death of the patient (all causes deaths, cardiac deaths)
Measured: 12 months
slope of GFR change
Measured: 12 months
"death" of the kidney (initiation of renal replacement therapy)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startJan 2008
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: Lack of cooperation among centers, Financial reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anemia Working Group Romania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liliana Garneata, Anemia Working Group Romania
- Investigators
- Gabriel Mircescu, Professor, Study director, Dr Carol Davila Teaching Hospital of NephrologyTiberiu Nanea, Professor, Principal investigator, "Caritas" Teaching Hospital, BucharestLiliana Garneata, MD, PhD, Principal investigator, Dr Carol Davila Teaching Hospital of Nephrology Bucharest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384657
- Sponsor's protocol ID
- AWG_06_01
- Status last verified
- Dec 2017
- First submitted
- 5 Oct 2006
- Last updated
- 22 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Intravenous Iron Therapy for Anemia Correction in Patients With Severe Chronic Heart Failure and Concomitant Moderate Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT00384657
- Acronym / sponsor ID
- AWG_06_01
- Conditions
- Chronic Kidney Disease, Chronic Heart Failure, Anemia
- Keywords
- chronic heart failure, chronic kidney disease, anemia, intravenous iron
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of cooperation among centers, Financial reasons
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Anemia Working Group RomaniaUniversity, hospital or other
- Study start
- Jan 2008 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 6 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I | Experimental | Drug: iron sucroseiv iron sucrose |
| Group II | No intervention | –Patients will receive conventional treatment of Chronic Heart Failure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- persistent severe CHF: functional class NYHA III (marked limitation of physical activity - comfortable at rest, but less than ordinary activity results in shortness of breath and/or fatigue16); left ventricular ejection fraction (echocardiography) less than 40%; functional and systolic dysfunction criteria must be stable at two different examinations one month apart;
- stable stage 3 chronic kidney disease: estimated GFR between 30-59mL/min/1.73m2 (mean value of three measurements within the last 8 weeks, separated from each other by at least one week); stable renal function (at least three different measurements within the past 8 weeks, separated from each other by at least one week; the difference between the highest and the lowest value should be less than 5mL/min/1.73m2)
- mild to moderate anemia: hemoglobin levels < 12g/dL (mean value of three measurements within the last 8 weeks, separated from each other by at least one week) and stable (at least three measurements within the last 8 weeks; the difference between the highest and the lowest value should be less than 1.5g/dL);
- iron deficiency: absolute (serum ferritin < 100ng/mL) or functional (serum ferritin 100-300ng/mL and transferrin saturation < 20%)
Key exclusion criteria (30 listed)
- evidence of active gastrointestinal or genital tract bleeding
- folate or vitamin B12 deficiency
- hypothyroidism
- hemolytic anemia
- any primary kidney diseases (glomerulonephritis, interstitial nephritis, cystic diseases)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iron sucroseAlso: Group I - iv iron group, Group II - conventional treatment groupPatients 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. | Drug | Group I |
Primary outcome
percentage of patients with increased ejection fraction
Time frame: 12 months
12 secondary outcomes
the need for blood transfusions during the study period
Time frame: 12 months
serum ferritin level
Time frame: 12 months
transferrin saturation
Time frame: 12 months
radial myocardial velocities
Time frame: 12 months
right ventricular function
Time frame: 12 months
global diastolic function
Time frame: 12 months
left ventricular mass index
Time frame: 12 months
major cardiovascular events (myocardial infarction, acute pulmonary edema, stroke)
Time frame: 12 months
hospital admissions
Time frame: 12 months
death of the patient (all causes deaths, cardiac deaths)
Time frame: 12 months
slope of GFR change
Time frame: 12 months
"death" of the kidney (initiation of renal replacement therapy)
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriel Mircescu, Professor study director
Dr Carol Davila Teaching Hospital of Nephrology
Tiberiu Nanea, Professor principal investigator
"Caritas" Teaching Hospital, Bucharest
Liliana Garneata, MD, PhD principal investigator
Dr Carol Davila Teaching Hospital of Nephrology Bucharest
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing iron sucrose in people with Chronic Kidney Disease and Chronic Heart Failure, run by Anemia Working Group Romania at 2 sites in Romania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
percentage of patients with increased ejection fraction (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2017.