E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vitamin K deficiency is highly prevalent among renal transplant recipients, promotes vascular calcification, and is associated with an increased risk of cardiovascular disease. Supplementation of vitamin K among renal transplant recipients is postulated to be associated with improvement of vascular calcification.
Study population: Outpatients (age ≥ 18 years), renal transplant recipients with vitamin K deficiency. |
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E.1.1.1 | Medical condition in easily understood language |
Effect of vitamin K supplementation on vascular calcification among renal transplant recipients with a vitamin K deficiency. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
Investigate the effect of vitamin K2 supplementation on serum calcification propensity in vitamin K deficient RTRs. |
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E.2.2 | Secondary objectives of the trial |
Investigate the effect of vitamin K2 supplementation on vitamin K status and vascular stiffness in vitamin K deficient RTRs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1. Age ≥18 years
2. Male and female renal transplant recipients
3. Participant of TransplantLines
4. Vitamin K deficient; dp-ucMGP >500 pmol/L
5. eGFR > 20 ml/min/1.73m2
6. Signed informed consent |
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study:
1. Treatment with vitamin K antagonists or direct oral anticoagulants (DOAC)
2. Atrial fibrillation or other heart rhythm disorders causing an unreliable PWV measurement
3. Known coagulopathy
4. Active malignancy; exception treated basal cell or squamous cell carcinoma
5. Current or planned pregnancy or lactation
6. Known intestinal malabsorption |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline in serum calcification propensity at 12 weeks following treatment vitamin K or placebo supplementation (V2-V1).
Quantification of calcification propensity, i.e., the tendency to develop future calcifications, in serum: This test quantifies the calcification propensity by challenging the patient’s serum with supersaturated calcium and phosphate solutions. This leads to formation of particles mainly containing fetuin-A and albumin, called primary calciprotein particles (CPPs). These primary CPPs spontaneously undergo topological rearrangement and transform into secondary CPPs. The timing of the transformation depends on the individual composition of serum, and more specifically on the balance between calcification promoters and calcification-inhibiting factors. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
V1 (baseline)
V2 (end of study) |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include change from baseline in parameters of vitamin K status (e.g., dp-ucMGP) and vascular stiffness (i.e., pulse wave velocity) at 12 weeks. (V2-V1). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
V1 (baseline)
V2 (end of study) |
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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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |