E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
1 out of 100 children born extremely early, or more than 8 weeks before the expected date. 20% of these extremely preterm children shows a cerebral hemorrhage at birth, leading to a significantly increased risk for neurodevelopmental deficits through to cerebral palsy. Recombinant erythropoietin is approved as a drug for the prevention of anemia of prematurity. Retrospective analyzes of Epo-treated preterm infants show improved neurological development in children after cerebral hemorrhage. |
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E.1.1.1 | Medical condition in easily understood language |
To evaluate the effect of intravenously administered EPO (Recormon) as compared to placebo in very preterm infants with brain damage diagnosed in the first days of life on longterm neurodevelopment. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 |
Primary objective: At 5 years of age: Intelligence quotient (Kaufman Assessment Battery for Children, german version (K-ABC) |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives:
1) cerebral ultrasound (cUS) findings until discharge
2) At term equivalent age: Brain injury score assessed on brain MRI
3) At 24 months: Mental development (Bayley III), incidence of visual,
hearing and motor impairment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed written parental consent
- IVH (grade II-IV)
- GA < 32 0/7 weeks and/or BW < 1’500 g at birth. (Comment: There is a steep rise in the incidence of IVH with decreasing GA and decreasing BW)
- Chronological age < 8 d. (Comment: More than 96% of all cases of IVH happen within the first 5 d of life. In contrast, IVH in term infants is a rare event and follows a rather different clinical course.) |
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E.4 | Principal exclusion criteria |
- Genetically defined syndrome
- Severe congenital malformation adversely affecting life expectancy or neurodevelopment
- Admitted a priori for palliative care
- Unlikely to participate at 5-year follow-up examination
- Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial;
- patients enrolled in this EPO-repair study are not allowed to receive EPO for other purposes;
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E.5 End points |
E.5.1 | Primary end point(s) |
At 5 years of age: Intelligence quotient (Kaufman Assessment Battery for Children, german version (K-ABC) |
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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) |
1) cerebral ultrasound (cUS) findings until discharge
2) At term equivalent age: Brain injury score assessed on brain MRI
3) At 24 months: Mental development (Bayley III), incidence of visual,
hearing and motor impairment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ad 1) At term equivalent age
ad 2) At term equivalent age
ad 3) At 24 months |
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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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | Yes |
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 | 5 |
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 | 5 |