Comparison of rhBSSL With Placebo When Added to Infant Formula or Pasteurized Breast Milk During 4 Weeks of Treatment in Preterm Infants
Phase 3
Terminated
- Conditions
- Prevention of Growth Restriction
- Interventions
- Registration Number
- NCT01413581
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
The purpose of this study is to demonstrate that rhBSSL improves growth in preterm infants as compared with placebo.
- Detailed Description
The purpose of this study is to demonstrate that rhBSSL improves growth in preterm infants as compared with placebo. The infants should be born before week 32 of gestational age.
The study drug, rhBSSL or placebo, will be administered during a 4 week treatment period by adding it to either infant formula or pasteurized breast milk.
The study will also evaluate the safety and tolerability of rhBSSL.
Eligible patients will be randomized in a ratio of 1:1 (rhBSSL:placebo). The study consists of maximum 1 week screening period, a 4-week treatment period and a 2 year follow-up period.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 415
Inclusion Criteria
- Preterm infants born before week 32 of gestation.
- Preterm infant who is less than 33 weeks postmenstrual age at the time of randomization.
- Preterm infant who is appropriate for gestational age (AGA) or small for gestational age (SGA) at birth.
- Preterm infant who is receiving food enterally (bottle or gavage tube) at a level of at least 100 ml/kg/day at randomization.
- Preterm infant whose enteral feeding consists of only infant formula or only pasteurized breast milk at the time of inclusion, and who are expected to remain on only infant formula for 4 weeks, or only pasteurized breast milk for at least 2 weeks following treatment initiation.
- Preterm infant who is expected not to receive any fresh breast milk for 4 weeks following treatment initiation.
- Informed consent is obtained.
Exclusion Criteria
- Expected stay in the hospital is less than 4 weeks from the first dose of study drug.
- Criteria to ensure no disease or treatment affecting growth or development, e.g. brain disease, necrotizing enterocolitis.
- Enrolled in another concurrent clinical intervention study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description rhBSSL rhBSSL (recombinant human bile-salt-stimulated lipase) rhBSSL (recombinant human bile-salt-stimulated lipase) Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method Growth velocity in grams per kilogram per day during 4 weeks of treatment. Baseline and Day 29
- Secondary Outcome Measures
Name Time Method Bayley Scale of Infant and Toddler Development, third edition: Social-emotional domain composite score at 24 months' corrected age 24 months' corrected age Bayley Scale of Infant and Toddler Development, third edition: Adaptive behavior domain composite score at 24 months' corrected age 24 months' corrected age Change from baseline in body weight (g) at 3 months Baseline and Month 3 Total body length (mm) at 12 months' corrected age 12 months' corrected age Total body height (cm) at 24 months' corrected age 24 months' corrected age Growth restriction Day 29 Defined as growth velocity \<15 gram per kilogram bodyweight per day during 4 weeks of treatment
Head circumference (mm) at 12 months' corrected age. 12 months´ corrected age Head circumference (mm) at 24 months' corrected age. 24 months´ corrected age Time from baseline to 150 mL/kg/day of enteral feeding Date of first dose and date 150 mL/kg/day of enteral feeding achieved (or exceeded) Re-admission to hospital within 1 month of discharge Date of discharge and date of re-admission Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score 12 months' corrected age 12 months' corrected age Body weight (g) at 24 months' corrected age 24 months´ corrected age Change from baseline in total body length (mm) at 4 weeks Baseline and Day 29 Change from baseline in total body length (mm) at 3 months Baseline and Month 3 Body weight (g) at 12 months' corrected age 12 months´ corrected age Change from baseline in head circumference (mm) at 3 months. Baseline and Month 3 Time to readiness for discharge Baseline and date of readiness for discharge Time until each of the following are fulfilled
* sustained weight gain (weight of 1800 g sustained for three days)
* ability to maintain normal body temperature
* ability to suckle feed
* ability to maintain stable cardiorespiratory functionTime to discharge Baseline and date of discharge Change from baseline in head circumference (mm) at 4 weeks. Baseline and Day 29 Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score at 24 months' corrected age 24 months' corrected age Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 12 months' corrected age 12 months' corrected age Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 24 months' corrected age 24 months' corrected age Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 12 months' corrected age 12 months' corrected age Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 24 months' corrected age 24 months' corrected age Neurodevelopment Disability Composite 24 months' corrected age Presence of :
* Composite score of less than 70 on any of the cognitive, language or motor domains of Bayley scale of infant and toddler development, third edition
* Bilateral deafness
* Bilateral blindness
* Cerebral palsyChild Behavior Checklist total problem score at 24 months' corrected age 24 months' corrected age visit Number of patients with at least one treatment emergent Adverse Event Day 29 and Month 3 Total and by system organ class and preferred term (coded by MedDRA)
Number of patients with at least one treatment emergent Serious Adverse Event Day 29 and Month 3 Total and by system organ class and preferred term (coded by MedDRA)
Number of patients with at least one Serious Adverse Drug Reaction 12 months' corrected age and 24 months' corrected age Total and by system organ class and preferred term (coded by MedDRA)
Level of Vitamin A (nmol/L) at 4 weeks Day 29 Level of Vitamin D (nmol/L) at 4 weeks Day 29 Number of outpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age Date of initial hospital discharge to home to date of 24 months' corrected age Number of inpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age Date of initial hospital discharge to home to date of 24 months' corrected age Number of days of hospitalization from the time of initial hospital discharge to home up to 24 months' corrected age Date of initial hospital discharge to home to date of 24 months' corrected age Number of days in intensive care unit from the time of initial hospital discharge to home up to 24 months' corrected age Date of initial hospital discharge to home to date of 24 months' corrected age Number of days lost from work related to the child's condition from the time of initial hospital discharge to home up to 24 months' corrected age Date of initial hospital discharge to home to date of 24 months' corrected age Presence of chronic medical conditions/diagnoses at 24 months' corrected age 24 months' corrected age Docosahexaenoic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks Day 29 Docosahexaenoic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks Day 29 Arachidonic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks Day 29 Arachidonic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks Day 29 Number of patients with antibodies to rhBSSL at 4 weeks Day 29 Number of patients with antibodies to rhBSSL at Month 3 Month 3 Number of patients with antibodies to rhBSSL at 12 months' corrected age 12 months' corrected age
Trial Locations
- Locations (1)
Swedish Orphan Biovitrum Investigational Site
🇸🇪Umeå, Sweden