E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To determine whether early and prolonged supply of ARA and DHA improves quality of growth and clinical outcomes in extreme premature infants as compared to our present nutrient supply. By closely assessing nutritional intake, anthropometric measures, clinical outcomes and several biomarkers of inflammation and metabolism, we hope to elucidate mechanisms of inflammation and metabolic mediated damage to major organs such as brain, lung, eye and cardiovascular system of extremely premature infants. |
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E.1.1.1 | Medical condition in easily understood language |
We want to study the effects of DHA and ARA supplementation on
1) brain maturation and cognition
2) bodycomposition and cardiovascular disease risk
3) typical diseases of extreme premature infants |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 |
To assess the effects of an early nutritional intervention on clinical outcomes and quality of growth in extreme premature infants (gestational age < 29 weeks).
Main hypothesis: Early, enhanced supply of the essential FAs DHA and ARA will improve brain growth and maturation, as compared to standard nutrient supply.
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E.2.2 | Secondary objectives of the trial |
To explore potential differences in inflammatory and metabolic pathway responses related to nutrient supply, age, sex, comorbidities, as well as pre- and postnatal growth.
Secondary hypotheses: Early, enhanced supply of the essential FAs DHA and ARA will improve quality of growth and cognitive development and it will reduce the frequency of inflammation-related neonatal comorbidities and long-term cardiovascular disease risk.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All extremely preterm infants born at OUH between 01.09.17 and 31.12.19 with GA<29 weeks are eligible.
Oral consent to participate is needed before inclusion. As soon as possible, and at latest within 24 hours of life, the caregivers will be introduced to all study details and the ICF has to be signed before further participation. |
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E.4 | Principal exclusion criteria |
congenital malformations, chromosomal abnormalities and critical illness with short life expectancy |
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E.5 End points |
E.5.1 | Primary end point(s) |
Brain maturation assessed by MRI with spectroscopy (MRS) and diffusion tensor imaging (DTI) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Term equivalent age (+/- 2 weeks). |
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E.5.2 | Secondary end point(s) |
1) Nutritional intakes
2) Anthropometric measurements: Weight nadir, time to regain birth weight, change in weight, length and HC (absolute and z-scores), and growth velocity from birth to 28 days and 36 weeks postmenstrual age (PMA), and at 3, 6, 12 and 24 months as well as 8 years CA.
3) Body composition
4) The cumulative incidence of neonatal morbidities associated with inflammation (BPD, ROP, NEC, WMI, and late onset septicemia). The frequency of persistent ductus arteriosus, postnatal growth restriction, hyperglycemia and hypotension.
5) Inflammatory, metabolic and nutrient markers in blood, urine and feces.
6) Neurodevelopment assessed by neurological and neuropsychological examinations as well as sophisticated neuroimaging modalities and neurophysiological tests.
7) Cardiovascular health assessed by echocardiography (both structural and functional) and with blood pressure (BP) measurements.
8) Lung function |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) daily during neonatal hospitalization
2) during neonatal hospitalization: weight daily, HC/lenght weekly; thereafter as given above.
3) at 36 weeks PMA, 6 months, and 8 years CA
4) short-time clinical outcomes will be registrered during neonatal hospitalization
5) days 0,1,2,3,5,7,14,21,28, and at 32 and 36 weeks PMA as well as at 3, 6, 12, and 2 and 8 years CA.
6) cerebral ultrasound and EEG at days 0,1,2 and at 32 and 36 weeks PMA. EEG also at 24 months CA. Standardized neurological examination and neuropsychological test (Bayley III) at 2 years CA. MRI at 8 years CA.
7) Echocardiography at days 0,1,2 and at 36 weeks PMA as well as at 2 and 8 years CA
8) Lung function at 36 weeks PMA and at 2 and 8 years CA |
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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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 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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After inclusion of 50 infants an interim analysis to evaluate possible negative effects of the intervention will be performed by an independent interim group. The results will be evaluated in partnership between the interim group and the collaborating partners to assess further plan for the project. |
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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 | 0 |