Iron-deficiency
Conditions
Keywords
Injectafer, ferric carboxymaltose, Supplemental Iron
Brief summary
The purpose of this study is to better understand how body levels of iron affect the ability to exercise in patients with heart failure (HF). Heart failure is a condition in which abnormal pumping action of the heart reduces the flow of blood to the body. Patients with heart failure may feel shortness of breath or leg fatigue when they exercise. Iron is an essential nutrient in the diet. In heart failure patients, low body levels of iron might increase shortness of breath and fatigue.
Detailed description
The purpose of this prospective, double blind parallel group randomized study is to compare the effects of ferric carboxymaltose vs. placebo on skeletal muscle mitochondrial oxidative capacity, submaximal exercise tolerance, and health-related quality of life in non-anemic Heart Failure (HF) patients with functional iron deficiency.
Interventions
DRUGFerric Carboxymaltose
Intravenous Ferric Carboxymaltose 750 mg mixed under sterile conditions in 100 ml of normal saline for final concentration of 7.5 mg/ml and administered via volumetric infusion pump over 15 minutes.
DRUGPlacebo
100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.
DEVICE31P MRS/MRI
Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments.
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Symptomatic NYHA Class II-III heart failure \>3 months * Guideline-recommended heart failure treatment for \> 3 months * Hemoglobin \>13 g/dl for men and \>12 g/dl for women * Functional iron deficiency (defined as serum ferritin level \<100 ng/ml or between 100 and 299 ng/ml with transferrin saturation \<20%) * Left ventricular ejection fraction \<40%, or left ventricular ejection fraction ≥40% with left atrial enlargement (left atrial volume index \>28 ml/m2) and/or left ventricular hypertrophy (left ventricular mass index \>95 g/m2 (women) or \>115 g/m2 (men) determined by echocardiogram within last 24 months. * Able and willing to provide written informed consent
Exclusion criteria
* Presence of implantable defibrillator, permanent pacemaker, other metal implant not compatible with 3TMRS/MRI, or other contraindication to 3T MRS/MRI procedures * Heart failure due to infiltrative cardiomyopathy, restrictive cardiomyopathy, or hypertrophic cardiomyopathy * Weight \<50 kg or \>120 kg * Coronary or cerebral atherothrombotic events in the past 6 months * Hospitalization of emergency room visit for heart failure within past 3 months * ICD shock in last 3 months * Known peripheral artery disease or ankle-brachial index \<0.9 at screening visit * Exercise primarily limited by angina, lung disease or neuromuscular disease * Systolic blood pressure \<100 or \>160 mmHg * Heart rate \<50 or \>110 min-1 * Estimated glomerular filtration rate \<30 ml/min * Liver function tests \>3 times upper limit of normal * Serum phosphate below normal limit * Pregnant or breast-feeding women * Women of child-bearing potential unwilling to use recommended contraception methods during the study * Treatment with oral iron supplements (except multivitamins) in past year * Treatment with intravenous iron in past year * Treatment with erythropoiesis stimulating agents in the past year * Known intolerance of intravenous iron * History of anaphylaxis * Participation in another clinical trial within last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Post-Exercise Phosphocreatine Recovery Time | Baseline, Week 4 | Post-exercise phosphocreatine recovery time (in seconds) will be used to assess mitochondrial oxidative capacity. It is measured non-invasively with 31P-magnetic resonance spectroscopy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 6-Minute Walk Test Distance | Baseline, Week 4 | The 6-minute walk test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire Score | Baseline, Week 4 | 23-item self-assessment of symptoms, physical and social limitations, and quality of life in patients with heart failure. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best. The total score ranges from 0-100, with higher scores indicating better health status. An increase in scores indicates health status improved during the observational period. |
| Change From Baseline in Hemoglobin Levels | Baseline, Week 4 | Hemoglobin is a protein in red blood cells that carries oxygen. Hemoglobin levels (g/dL) were measured in laboratory analyses using patient blood samples. |
| Change From Baseline in Serum Ferritin Levels | Baseline, Week 4 | Ferritin is a blood protein that contains iron. Serum ferritin levels (ng/ml) were measured in laboratory analyses using patient blood samples. |
| Change From Baseline in Transferrin Saturation | Baseline, Week 4 | Transferrin saturation, measured as a percentage, is the value of serum iron divided by the total iron-binding capacity of the available transferrin. Transferrin saturation was measured in laboratory analyses using patient blood samples. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferric Carboxymaltose HF patients with functional iron deficiency assigned to receive one-time dose of Ferric Carboxymaltose 750 mg. Participants will undergo serial assessment before and 4 weeks after study drug administration
Ferric Carboxymaltose: Intravenous Ferric Carboxymaltose 750 mg mixed under sterile conditions in 100 ml of normal saline for final concentration of 7.5 mg/ml and administered via volumetric infusion pump over 15 minutes.
31P MRS/MRI: Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments. | 3 |
| Placebo HF patients with functional iron deficiency assigned to receive one-time dose of Placebo (saline injection). Participants will undergo serial assessment before and 4 weeks after study drug administration.
Placebo: 100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.
31P MRS/MRI: Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Ferric Carboxymaltose | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 9.85 | 60.67 years STANDARD_DEVIATION 11.64 | 56.3 years STANDARD_DEVIATION 13.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Change From Baseline in Post-Exercise Phosphocreatine Recovery Time
Post-exercise phosphocreatine recovery time (in seconds) will be used to assess mitochondrial oxidative capacity. It is measured non-invasively with 31P-magnetic resonance spectroscopy.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose | Change From Baseline in Post-Exercise Phosphocreatine Recovery Time | -0.21 seconds | Standard Deviation 4.66 |
| Placebo | Change From Baseline in Post-Exercise Phosphocreatine Recovery Time | -27.26 seconds | Standard Deviation 49.27 |
Secondary
Change From Baseline in 6-Minute Walk Test Distance
The 6-minute walk test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose | Change From Baseline in 6-Minute Walk Test Distance | -12.5 meters | Standard Deviation 17.4 |
| Placebo | Change From Baseline in 6-Minute Walk Test Distance | 54.6 meters | Standard Deviation 29 |
Secondary
Change From Baseline in Hemoglobin Levels
Hemoglobin is a protein in red blood cells that carries oxygen. Hemoglobin levels (g/dL) were measured in laboratory analyses using patient blood samples.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose | Change From Baseline in Hemoglobin Levels | -0.2 Hemoglobin levels (g/dL) | Standard Deviation 0.4 |
| Placebo | Change From Baseline in Hemoglobin Levels | 0.1 Hemoglobin levels (g/dL) | Standard Deviation 0.6 |
Secondary
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Score
23-item self-assessment of symptoms, physical and social limitations, and quality of life in patients with heart failure. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best. The total score ranges from 0-100, with higher scores indicating better health status. An increase in scores indicates health status improved during the observational period.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose | Change From Baseline in Kansas City Cardiomyopathy Questionnaire Score | 8.7 score on a scale | Standard Deviation 13.3 |
| Placebo | Change From Baseline in Kansas City Cardiomyopathy Questionnaire Score | 14 score on a scale | Standard Deviation 10.6 |
Secondary
Change From Baseline in Serum Ferritin Levels
Ferritin is a blood protein that contains iron. Serum ferritin levels (ng/ml) were measured in laboratory analyses using patient blood samples.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose | Change From Baseline in Serum Ferritin Levels | 299.7 Serum ferritin levels (ng/ml) | Standard Deviation 118.1 |
| Placebo | Change From Baseline in Serum Ferritin Levels | 2 Serum ferritin levels (ng/ml) | Standard Deviation 7.2 |
Secondary
Change From Baseline in Transferrin Saturation
Transferrin saturation, measured as a percentage, is the value of serum iron divided by the total iron-binding capacity of the available transferrin. Transferrin saturation was measured in laboratory analyses using patient blood samples.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferric Carboxymaltose | Change From Baseline in Transferrin Saturation | 10.5 percent (%) | Standard Error 10 |
| Placebo | Change From Baseline in Transferrin Saturation | 0.3 percent (%) | Standard Error 5.1 |