E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Iron deficiency in kidney transplant recipients |
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E.1.1.1 | Medical condition in easily understood language |
Iron shortage after kidney transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10022971 |
E.1.2 | Term | Iron deficiencies |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study the effects of FCM on exercise tolerance in iron-deficient kidney transplant recipients (KTR’s). |
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E.2.2 | Secondary objectives of the trial |
To study the effects of FCM on haematinic parameters, quality of life, cardiac function, muscle function, bone and mineral parameters, focus, microbiota, the immune system, the incidence of infections, allograft failure and mortality in iron-deficient kidney transplant recipients (KTR’s). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Coronavirus vaccination substudy of the EFFECT-KTx study (COVAC-EFFECT)
Date: 24-2-2021
Version: 1 |
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E.3 | Principal inclusion criteria |
1. Kidney transplant recipient
2. Iron deficiency, defined by a ferritin level of ≤100 ug/L, or 100-299 ug/L combined with a transferrin saturation of ≤20%
3. At least four months after transplantation at the time of inclusion (and six months after transplantation at baseline)
4. Age ≥18 years
5. Ability to comply with the study protocol
6. Informed consent
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E.4 | Principal exclusion criteria |
1. Intolerance of any intravenous iron solution
2. Severe anemia (Hb <10.4 g/dL, <6.5 mmol/L), microcytic anemia or progressive anemia (˃1 mmol/L per month decline for two months or more)
3. A positive feces occult blood test or otherwise demonstrated gastrointestinal, or urogenital, blood loss
4. Blood transfusion in the past six weeks
5. Polycythemia (Hb >15.3 g/dL, 9.5 mmol/L)
6. History of haemochromatosis
7. An estimated glomerular filtration rate (eGFR) of ≤ 30 ml/min per 1.73 m2 at screening.
8. Resting heart rate of more than 120 per minute
9. Unstable angina or myocardial infarction during the previous month
10. Disability to walk
11. Severe hypophosphatemia in the month before baseline (serum phosphate <0.35 mmol/L)
12. Pregnancy or inability to take adequate contraceptive measures when at childbearing age
13. Severe hyponatremia (Na <130 mmol/L) or fluid overload
14. Participation in another interventional study
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E.5 End points |
E.5.1 | Primary end point(s) |
The main study endpoint of the EFFECT-KTx study is change in exercise tolerance, quantified by the six-minute walk test (6MWT) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After a maximum of four dosages of ferric carboxymaltose compared to placebo. |
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E.5.2 | Secondary end point(s) |
Secondary study endpoints of the EFFECT-KTx study are changes, between t=0 and t=24 weeks and between the intervention and the control group, in:
• Haematinic and iron parameters: haemoglobin, haematocrit, mean corpuscular volume (MCV), free serum iron, serum ferritin, serum transferrin, serum hepcidin and C-reactive protein
• Systolic and diastolic cardiac function analysed with a transthoracic echocardiography measuring left ventricular ejection fraction (LVEF), diastolic function and strain; serum NTproBNP and high-sensitive troponin-T
• Quality of life, assessed by the Short-Form-36 (SF-36) questionnaire, the Kidney Disease Quality of Life Test (KDQOL-SF), the Checklist Individual Strength (CIS) and the 5Dimensial EuroQol (EQ-5D) instrument
• Muscle strength, measured by neurological physical examination of the major muscle groups, the ‘Five-Times-Sit-to-Stand-test (FTSTS), the Timed-up-and-Go test (TUG) and a handgrip dynamometry
• Cognitive performance, measured by: the dutch version of the National Adult Reading Test, the Digit Span which is a component of the Wechsler Adult Intelligence Scale, a dutch version of the Rey Auditory Verbal Learning Test, the Cognitive Screening Test, the Trial Making Test, the Clock Drawing Test, the Word Fluency subtest of the Groninger Intelligentietest, the Controlled Oral Word Association Test, the Symbol Digit Modalities Test and the Key Search Test
• Parameters of phosphate and bone metabolism:
- Serum: phosphate, calcium, vitamin D, vitamin D3, parathyroid hormone, total FGF23 and intact FGF23
- 24-hour urine: phosphate, calcium
• Characteristics of the immune system: peripheral blood mononuclear cell (PBMC) count, macrophage count, T-lymfocyte count, B-cell count, neutrophil count and analysis of cytokines
• Hepatic parameters: serum aspartate aminotransferase and alanine aminotransferase
• Parameters of kidney function and injury:
- Blood: creatinin
- Urine: MCD1, CD163, CD25, FOXP3 mRNA, kidney injury marker 1 (KIM-1)
• Intestinal microbiota
• Blood Pressure
• Occurrence of clinical events: infectious diseases, cardiovascular events, graft rejection and mortality
• COVAC-EFFECT substudy: T-lymphocyte and antibody response against SARS-CoV2 after vaccination (after a minimum of one dose of ferric carboxymaltose or placebo)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After a maximum of four dosages of ferric carboxymaltose compared to placebo. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last participant |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |