E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Very low birth weight infants requiring intensive care have relative insulin deficiency often leading to hyperglycaemia during the first week of life. There is increasing evidence that the early postnatal period is critical for pancreatic development. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment. |
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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 investigate whether an early fixed dose insulin infusion, combined with variable dextrose support to maintain normoglycaemia, will reduce mortality at 28 days of age in the very low birth weight neonate. |
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E.2.2 | Secondary objectives of the trial |
total number of days in neonatal intensive care prior to discharge home; (ii) episodes of sepsis in the first 2 weeks of life; (iii) growth at 28 days; (iv) severity of retinopathy of prematurity; (v) incidence of necrotizing enterocolitis (vi) incidence of intracranial haemorrhage (vii) chronic lung disease (viii) mortality before expected date of delivery
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
i) <1500g ii) <24 hours of age iii) Requiring intensive care and in whom it is considered appropriate to continue intensive care
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E.4 | Principal exclusion criteria |
i) Maternal diabetes including gestational diabetes ii) Babies where the appropriateness of continuing intensive care is being discussed iii) Major congenital anomalies
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy outcomes (i) Blood glucose control over the first week of life as assessed by the MiniMed subcutaneous continuous glucose monitor (CGMS) Primary outcome: Death within and including the first 28 days after delivery (where day 1 is considered as the first day of life) Secondary outcomes: i. Days of Neonatal Intensive Care: As defined by BAPM 200140 (appendix 1). ii. Episodes of sepsis in the first 2 weeks: a) Culture positive systemic infection will be defined as microbiologically positive cultures of blood, cerebrospinal fluid or suprapubic aspirate of urine plus clinical signs of sepsis. b) Culture negative infection will be defined as clinical signs suggestive of sepsis and considered to warrant >48 hours of antibiotics but with negative cultures. iii. Growth: All babies will have measurements of weight, length and head circumference at birth and every seven completed days after recruitment until 28 days of age. Growth will be assessed as change in weight, length and head circumference standard deviation score (SDS) from birth to 28 days of age. iv. Retinopathy of Prematurity: All these babies will be routinely screened (appendix 1), for retinopathy of prematurity and will be graded using the internationally recognised grading system 41,42 (appendix 1). Infants will be classified by the most severe degree of retinopathy. v. Incidence of necrotizing enterocolitis: defined as radiological evidence of necrotizing entercolitis assessed by consultant radiologist (appendix 1). vi. Incidence of intracranial haemorrhage: defined as cranial ultrasound evidence as assessed by Consultant Neonatologist (appendix 1). vii. Chronic Lung disease: defined as respiratory support or oxygen dependency at 36 weeks corrected gestational age 43 (appendix 1) viii. Death before expected date of delivery: taken as date considered to be most accurate estimate of delivery date Efficacy: i. Percent of time normoglycaemic: All babies will have a continuous glucose sensor in situ for the 7 completed days. Sensors will be inserted within 24 hours of birth and left in situ for 7 complete days from the time of insertion. This will take a measure of interstitial glucose every 5 minutes and will give an assessment of glucose control throughout the first week. The percent of time spent with blood glucose <2.6mmol/l, 2.6-10.0mmol/l, >10 mmol/l and <4.0, 4.0-8.0mmol/l, >8.0mmol/l will be measured. ii. IGF-I and IGFBP-1: measured in blood taken on days 1, 3, 8 and 28 iii) cytokines: measured in blood taken on days 1, 3, 8 and 28 iv) protein catabolism: measured by urinary 3-methylhistidine/creatinine ratio on day
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard treatment for VLBW infants |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Age of term (corrected gestational age) of last patient included. |
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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 |