Insulin-Like Growth Factor I (IGF-I) in the Prevention of Complications of Preterm Birth
This is a randomized multicenter trial on pharmacokinetics, safety and efficacy with administration of Insulin-Like Growth Factor I (IGF-I) in preterm infants to prevent complications of preterm birth.
Retinopathy of Prematurity
Drug: mecasermin rinfabate
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Determination of the rhIGF-I/rhIGFBP-3 Dose, Administered as a Continuous Infusion, Required to Establish and Maintain Longitudinal Serum IGF-I Levels Within Physiological Levels in Premature Infants, to Prevent Retinopathy of Prematurity.|
- Severity of retinopathy of prematurity [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
- Incidence of mild and severe bronchopulmonary dysplasia [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
- Body weight [ Time Frame: At birth, day 1, 2 and 3 and thereafter twice weekly up post menstrual age week 40 (appr.) ] [ Designated as safety issue: No ]Development of body weight in treated infants will be compared with untreated controls
- Length [ Time Frame: Once weekly up to End of Study (at term age (post menstrual week 40)) ] [ Designated as safety issue: No ]Development of length in treated infants will be compared with untreated controls
- Brain volume and head circumference [ Time Frame: Study days 1, 3, 7, 14, 21 and at PMA 6 weeks and at term age (post menstrual week 40) ] [ Designated as safety issue: No ]Development of brain volume and head circumference in treated infants will be compared with untreated controls
- Number of days in neonatal intensive care [ Time Frame: At home discharge ] [ Designated as safety issue: No ]Total number of days in neonatal intensive care prior to home discharge for treated infants will be compared with untreated controls
- Adverse events [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]Hematology, clinical chemistry, physical examinations and vital signs including heart rate, blood pressure, oxygen saturation and breath frequency will be monitored from birth throughout the study.
- IGF-I levels [ Time Frame: From day of birth up to end of study ] [ Designated as safety issue: No ]IGF-I levels and associated pharmacokinetic parameters during and after continuous infusion of rhIGF-I/rhIGFBP-3 will be monitored from day of birth up to study end (postmenstrual week 40)
- Blood glucose levels [ Time Frame: Throughout the treatment period ] [ Designated as safety issue: Yes ]
- Long term follow up [ Time Frame: At 2.5 and 5.5 years of age ] [ Designated as safety issue: Yes ]All infants will be screened at 2.5 and 5.5 years of age with regard to visual development. Ocular fundus photographs for digital image analysis of the retinal vascular morphology will be taken at 2.5 and 5.5 years and at 5.5 years of age the children will have a clinical physical examination, including ultrasound of heart, kidney and spleen size, as well as a test of neuropsychologic functions (e.g. WISC) and test of pulmonary function. The pubertal development will be investigated by a pediatric endocrinologist at 10.5 years for the girls and at 12 years for the boys.
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
No Intervention: No IGF-I administration
Standard neonatology care without administration of IGF-I
Drug: mecasermin rinfabate
Continuous intravenous infusion
Other Name: IGF-I
Low Insulin-Like Growth Factor I (IGF-I) levels in premature infants between gestational ages of 23 and 40 weeks is a predictor of ROP. Restoration of IGF-I to normal in uteri levels may prevent ROP by allowing normal vessel growth and survival. An increase of serum IGF-I levels to approximately reach the level for corresponding gestational age (GA) of 20-60 μg/L, thus bringing levels to within physiological range, may prevent development of ROP.
In a phase-I pharmacokinetic study, the amount of recombinant human IGF-I (rhIGF-I), administered as a single infusion over three hours, required to produce Postmenstrual Age (PMA) levels of IGF-I within the normal intrauterine range for corresponding Gestational Age (GA)in premature infants was established. An algorithm was developed to predict the appropriate individual dose to reach levels of IGF-I corresponding to intrauterine levels when administering rhIGF-I as a continuous intravenous infusion.
In the present study, the dose of rhIGF-I needed, when administered as continuous infusion, to keep the PMA levels of IGF-I within the normal intrauterine range for corresponding GA from day after birth (study day 1) and up to and including maximally PMA age 31 weeks + 6 days (which is the same anticipated approach of a future preventive treatment), will be investigated. Moreover, the outcome on ROP development and other efficacy endpoints by increasing and maintaining the IGF-I levels to within intrauterine levels will be compared to a control group randomized to receive standard neonatal care without administration of study drug
|Gothenburg University Hospital|
|Lund University Hospital|
|Karolinska University Hospital|
|Principal Investigator:||David Ley, MD, PhD||Lund University Hospital, Sweden|
|Principal Investigator:||Niklasson Aimon, MD, PhD||Gothenburg University Hospital, Sweden|
|Principal Investigator:||Boubou Hallberg, MD, PhD||Karolinska University Hospital|