E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Critically ill children with severe vitamin D deficiency |
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E.1.1.1 | Medical condition in easily understood language |
Children with severe vitamin D deficiency |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047626 |
E.1.2 | Term | Vitamin D deficiency |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 determine whether a weight based enteral loading dose protocol can rapidly normalize vitamin D levels in critically ill children |
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E.2.2 | Secondary objectives of the trial |
To evaluate whether the weight based vitamin D loading protocol, when compared with usual care, results in:
1. Greater occurrence of vitamin D related adverse events (e.g. hypercalcemia, hypercalciuria)
2. Improved vitamin D axis functioning (e.g. active hormone levels, calcium metabolism)
3. Differences in blood measures of inflammation and innate immunity (e.g. CRP, procalcitonin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The inclusion criteria for this study are:
Admitted to ICU,
Corrected gestational age > 37 weeks to age < 18 years,
Expected ICU admission in excess of 48 hours, and will have access for bloodwork at 7 days (clinical bloodwork or lines)
Blood 25(OH)D less than 50 nmol/L (regardless of prior approach to supplementation), |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded:
Significant gastrointestinal disorder preventing enteral drug administration (e.g. necrotizing enterocolitis);
Hypercalcemia (excluding transient abnormalities and those related to parenteral calcium administration for hypocalcemia);
Confirmed or suspected William’s syndrome;
Patient known to have nephrolithiasis or Nephrocalcinosis;
Imminent plan for withdrawal of care or transfer to another ICU;Physician refusal;
Previous enrollment in the study;
Patient known to have granulomatous disease (tuberculosis or sarcoidosis),
Severe liver dysfunction/liver failure;
Patient know to have hypersensitivity or allergy to vitamin D or any of the non-medicinal ingredients of the formulation;Patient on thiazide diuretics who is also receiving regular ongoing calcium supplementation above the daily recommended intake for reasons other than hypocalcemia;
Adolescent female of child-bearing age with a positive serum pregnancy test; or
Patient on digoxin-therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine whether loading dose therapy can rapidly normalize vitamin D status we will measure blood 25(OH)D concentration. More specifically, our primary outcome is the proportion of critically ill children who achieve blood 25(OH)D concentration above 75 nmol/L by day 7. 25(OH)D is widely regarded as the best indicator of vitamin D status |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Vitamin D related adverse events
Hypercalcemia – We will define hypercalcemia as an ionized calcium level above 1.40 mmol/L (children under 8 weeks as > 1.45 mmol/L)
Hypercalcuria – We will identify hypercalcuria using calcium-creatinine ratios, defined using age specific norms and thresholds |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |