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| Name | Class |
|---|---|
| Dutch Kidney Foundation | OTHER |
| Vifor Fresenius Medical Care Renal Pharma | INDUSTRY |
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Iron deficiency is common in kidney transplant recipients and is associated with impaired exercise tolerance and an unfavourable prognosis.
This multicentre double-blind, placebo-controlled randomized controlled clinical trial will allow the investigators to analyse the effects of intravenous iron correction with ferric(III) carboxymaltose on exercise tolerance and other parameters, in comparison to a placebo.
Rationale: Iron deficiency is common in kidney transplant recipients. The presence of iron deficiency is associated with an unfavourable prognosis in these patients. In patients with heart failure and iron deficiency, treatment with intravenous iron improved exercise capacity and quality of life. Whether such beneficial effects may also occur in kidney transplant recipients is unknown.
Objective: Our main objective is to address whether correction of iron deficiency with ferric(III) carboxymaltose improves exercise tolerance and quality of life in iron-deficient kidney-transplant recipients.
Study design: A multicentre double-blind, placebo-controlled randomized controlled clinical trial will be performed to compare the effects of ferric(III) carboxymaltose with placebo.
Study population: 158 iron-deficient kidney transplant recipients. The intervention arm will receive 10 mL of ferric(III) carboxymaltose (50 mg Fe3/mL, intravenously) every six weeks, with a total of four dosages. The control arm receives an intravenous placebo solution (saline).
Main study parameters/endpoints: The primary endpoint is the distance walked in six minutes, as quantified by the six-minute-walking-test at the end of follow-up.
The investigators expect that iron-deficient kidney transplant recipients will benefit from ferric(III) carboxymaltose treatment as a result of an improvement in exercise tolerance and general wellbeing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ferric(III) carboxymaltose | Active Comparator | The intervention group will be treated with four dosages of 500 mg iron in the form of 10 mL ferric(III) carboxymaltose dissolved in 240 mL of NaCl 0.9%, with interval periods of six weeks. |
|
| Placebo | Placebo Comparator | The placebo-controlled group will receive four dosages of 250 mL of NaCl 0.9% solution with interval periods of six weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ferric carboxymaltose | Drug | Four intravenous dosages of ferric(III) carboxymaltose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Exercise tolerance | The between-group difference in change in exercise tolerance quantified by the six-minute walk test (6MWT) | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Hemoglobin level | The between-group difference in change in hemoglobin level | 24 weeks |
| Iron status | The between-group difference in change in iron parameters (plasma iron, ferritin, transferrin saturation) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Martin de Borst, MD/PhD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | 9713 GZ | Netherlands | |||
| University Medical Center Utrecht |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36948568 | Derived | Vinke JS, Eisenga MF, Sanders JF, Berger SP, Spikman JM, Abdulahad WH, Bakker SJ, Gaillard CAJM, van Zuilen AD, van der Meer P, de Borst MH. Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial. BMJ Open. 2023 Mar 22;13(3):e065423. doi: 10.1136/bmjopen-2022-065423. |
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To protect participant privacy, public access to the dataset or individual participant data will not be provided. However, after deidentification of these data and after publication of the main results, requests for the re-use of all pseudo-anonymised individual participant data by researchers who provide a methodologically sound proposal for a secondary analysis or meta-analysis will be evaluated by the Principal Investigator. Data may be shared if the research question falls within the scope of the informed consent. Proposals should be directed to m.h.de.borst@umcg.nl and requestors will need to sign a data access agreement.
The study protocol, including a statistical data analysis plan, will be published in a peer-reviewed journal.
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| ID | Term |
|---|---|
| D018798 | Anemia, Iron-Deficiency |
| D000090463 | Iron Deficiencies |
| ID | Term |
|---|---|
| D000747 | Anemia, Hypochromic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C522335 | ferric carboxymaltose |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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The study is designed as a 24 week, multicentre, randomized placebo-controlled clinical trial with two parallel arms to investigate the effect of ferric(III) carboxymaltose on exercise tolerance, cardiac function, skeletal muscle function, quality of life, the gut microbiota and on the immune system, to be performed at the University Medical Center Groningen (UMCG) and the Erasmus MC, University Medical Center Rotterdam.
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All participants, care providers and researchers will be blinded, except for the nurse who will administer the medication.
| Sodium chloride | Drug | Four intravenous dosages of sodiumchloride |
|
|
| 24 weeks |
| Cardiac function | The between-group difference in change in cardiac structure, function and strain, analysed with a transthoracic echocardiography | 24 weeks |
| Muscle strength 1 | The between-group difference in change in muscle strength measured by the 'Five-Times-Sit-to-Stand-test (FTSTS) | 24 weeks |
| Muscle strength 2 | The between-group difference in change in muscle strength measured by the timed-up-and-Go test (TUG) | 24 weeks |
| Muscle strength 3 | The between-group difference in change in muscle strength measured by handgrip dynamometry | 24 weeks |
| Muscle mass | The between-group difference in change in muscle mass assessed using 24-hour urinary creatinine excretion | 24 weeks |
| Phosphate level | The between-group difference in change in phosphate level | 24 weeks |
| Calcium level | The between-group difference in change in calcium level | 24 weeks |
| Vitamin D status | The between-group difference in change in vitamin D level | 24 weeks |
| Parathyroid hormone | The between-group difference in change in parathyroid hormone level level | 24 weeks |
| FGF23 | The between-group difference in change in FGF23 level | 24 weeks |
| Intestinal microbiota | The between-group difference in change in intestinal microbiota | 24 weeks |
| Incidence of any infection | The between-group difference in incidence of infections | 24 weeks |
| Incidence of hospitalisation | The between-group difference in incidence of hospitalisation | 24 weeks |
| Incidence of cardiac events | The between-group difference in incidence of cardiac events | 24 weeks |
| Incidence of graft failure | The between-group difference in incidence of graft failure | 24 weeks |
| Lymphocyte production of cytokines | The between-group difference in lymphocyte cytokine espression (measured with facs) | 24 weeks |
| Lymphocyte production of immunoglobulins | The between-group difference in lymphocyte IgG production (measured with ELISA) | 24 weeks |
| Lymphocyte proliferation rate | The between-group difference in lymphocyte proliferation rate (assessed with FACS) | 24 weeks |
| B-lymphocyte differentiation rate | The between-group difference in B-lymphocyte plasma cell formation (assessed with Facs) | 24 weeks |
| Cognitive performance (memory span) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Forward Test, minimum value 0, maximum value 9, a higher score means a better outcome) | 24 weeks |
| Cognitive performance (verbal memory) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (15 word test, minimum value 0, maximum value 75, a higher score means a better outcome) | 24 weeks |
| Cognitive performance (semantic memory) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (Word Fluency Test, minimum value 0, no maximum value, a higher score means a better outcome) | 24 weeks |
| Cognitive performance (processing speed) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (symbol digit modalities test, minimum value 0, maximum value 110, a higher score means a better outcome) | 24 weeks |
| Cognitive performance (visuomotor and mental speed) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test A, minimum value 1, no maximum value, a lower score means a better outcome) | 24 weeks |
| Cognitive performance (cognitive flexibility) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test B, minimum value 1, no maximum value, a lower score means a better outcome) | 24 weeks |
| Cognitive performance (executive control) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (Controlled Oral Word Association Test, minimum score 1, no maximum score, a higher score means a better outcome) | 24 weeks |
| Cognitive performance (working memory) | The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Backward, minimum score 0, maximum score 8, a higher score means a better outcome) | 24 weeks |
| Plasma creatinine | The between-group difference in change in plasma creatinine | 24 weeks |
| Quality of Life (health) | The between-group difference in change in quality of life quantified with SF36 questionnaire. A higher score means a better outcome. | 24 weeks |
| Quality of Life (subjective fatigue) | The between-group difference in change in quality of life quantified with the Dutch Checklist individual Strength). A higher score means worse fatigue. | 24 weeks |
| Quality of Life (long-lasting fatigue) | The between-group difference in change in quality of life quantified with the Dutch Multifactor Fatigue Scale). A higher score means worse fatigue. | 24 weeks |
| Quality of Life (overall) | The between-group difference in change in quality of life quantified with EuroQol-5D-5L | 24 weeks |
| Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response | The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific antibody titre after vaccination. | 12 months |
| Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response | The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specif T-lymphocyte response after vaccination. | 12 months |
| Gastro-intestinal symptoms | The between-group difference in change in gastro-intestinal symptoms assessed with the gastrointestinal symptom rating scale. | 24 weeks |
| Hepatic injury | The between-group difference in change in plasma hepatic enzyme levels (aspartate transaminase and alanine transaminase) | 24 weeks |
| Restless legs | The between-group difference in prevalence of restless legs symptoms before and after treatment | 24 weeks |
| Kidney graft rejection and injury | The between-group difference in change in urine kidney injury marker levels | 24 weeks |
| Utrecht |
| Netherlands |
| D019189 |
| Iron Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D017670 |
| Sodium Compounds |