Clinical trial NCT01413581: Comparison of rhBSSL With Placebo When Added to Infant Formula or Pasteurized Breast Milk During 4 Weeks of Treatment in Preterm Infants
Official title: A Prospective, Randomized, Double-Blind, Phase 3 Study Comparing rhBSSL and Placebo Added to Infant Formula or Pasteurized Breast Milk During 4 Weeks of Treatment in Preterm Infants Born Before Week 32 of Gestational Age
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prevention of Growth Restriction
Keywords: rhBSSL
preterm infants
Swedish Orphan Biovitrum
growth velocity
Prevention of growth restriction
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2011-08-10
Enrollment: 415
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Growth velocity in grams per kilogram per day during 4 weeks of treatment.
timeFrame: Baseline and Day 29
Secondary outcomes:
measure: Change from baseline in body weight (g) at 3 months
timeFrame: Baseline and Month 3
measure: Body weight (g) at 12 months' corrected age
timeFrame: 12 months´ corrected age
measure: Body weight (g) at 24 months' corrected age
timeFrame: 24 months´ corrected age
measure: Change from baseline in total body length (mm) at 4 weeks
timeFrame: Baseline and Day 29
measure: Change from baseline in total body length (mm) at 3 months
timeFrame: Baseline and Month 3
measure: Total body length (mm) at 12 months' corrected age
timeFrame: 12 months' corrected age
measure: Total body height (cm) at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Growth restriction
timeFrame: Day 29
measure: Time to readiness for discharge
timeFrame: Baseline and date of readiness for discharge
measure: Time to discharge
timeFrame: Baseline and date of discharge
measure: Change from baseline in head circumference (mm) at 4 weeks.
timeFrame: Baseline and Day 29
measure: Change from baseline in head circumference (mm) at 3 months.
timeFrame: Baseline and Month 3
measure: Head circumference (mm) at 12 months' corrected age.
timeFrame: 12 months´ corrected age
measure: Head circumference (mm) at 24 months' corrected age.
timeFrame: 24 months´ corrected age
measure: Time from baseline to 150 mL/kg/day of enteral feeding
timeFrame: Date of first dose and date 150 mL/kg/day of enteral feeding achieved (or exceeded)
measure: Re-admission to hospital within 1 month of discharge
timeFrame: Date of discharge and date of re-admission
measure: Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score 12 months' corrected age
timeFrame: 12 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 12 months' corrected age
timeFrame: 12 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 12 months' corrected age
timeFrame: 12 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Social-emotional domain composite score at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Bayley Scale of Infant and Toddler Development, third edition: Adaptive behavior domain composite score at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Neurodevelopment Disability Composite
timeFrame: 24 months' corrected age
measure: Child Behavior Checklist total problem score at 24 months' corrected age
timeFrame: 24 months' corrected age visit
measure: Number of patients with at least one treatment emergent Adverse Event
timeFrame: Baseline and Day 29
measure: Number of patients with at least one treatment emergent Adverse Event
timeFrame: Day 29 and Month 3
measure: Number of patients with at least one treatment emergent Serious Adverse Event
timeFrame: Baseline and Day 29
measure: Number of patients with at least one treatment emergent Serious Adverse Event
timeFrame: Day 29 and Month 3
measure: Number of patients with at least one Serious Adverse Drug Reaction
timeFrame: 12 months' corrected age and 24 months' corrected age
measure: Level of Vitamin A (nmol/L) at 4 weeks
timeFrame: Day 29
measure: Level of Vitamin D (nmol/L) at 4 weeks
timeFrame: Day 29
measure: Number of outpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age
timeFrame: Date of initial hospital discharge to home to date of 24 months' corrected age
measure: Number of inpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age
timeFrame: Date of initial hospital discharge to home to date of 24 months' corrected age
measure: Number of days of hospitalization from the time of initial hospital discharge to home up to 24 months' corrected age
timeFrame: Date of initial hospital discharge to home to date of 24 months' corrected age
measure: Number of days in intensive care unit from the time of initial hospital discharge to home up to 24 months' corrected age
timeFrame: Date of initial hospital discharge to home to date of 24 months' corrected age
measure: 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
timeFrame: Date of initial hospital discharge to home to date of 24 months' corrected age
measure: Presence of chronic medical conditions/diagnoses at 24 months' corrected age
timeFrame: 24 months' corrected age
measure: Docosahexaenoic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks
timeFrame: Day 29
measure: Docosahexaenoic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks
timeFrame: Day 29
measure: Arachidonic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks
timeFrame: Day 29
measure: Arachidonic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks
timeFrame: Day 29
measure: Number of patients with antibodies to rhBSSL at 4 weeks
timeFrame: Day 29
measure: Number of patients with antibodies to rhBSSL at Month 3
timeFrame: Month 3
measure: Number of patients with antibodies to rhBSSL at 12 months' corrected age
timeFrame: 12 months' corrected age
Other outcomes:
Locations:
city: Bruges
country: Belgium
facility: Swedish Orphan Biovitrum Investigational Site
city: Leuven
country: Belgium
facility: Swedish Orphan Biovitrum Investigational Site
city: Liege
country: Belgium
facility: Swedish Orphan Biovitrum Investigational Site
city: Rocourt
country: Belgium
facility: Swedish Orphan Biovitrum Investigational Site
city: Wilrijk
country: Belgium
facility: Swedish Orphan Biovitrum Investigational Site
city: Hradec Kralove
country: Czech Republic
facility: Swedish Orphan Biovitrum Investigational Site
city: Olomouc
country: Czech Republic
facility: Swedish Orphan Biovitrum Investigational Site
city: Prague
country: Czech Republic
facility: Swedish Orphan Biovitrum Investigational Site
city: Zlin
country: Czech Republic
facility: Swedish Orphan Biovitrum Investigational Site
city: Amiens
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Lille
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Nancy
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Paris
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Rouen
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Strasbourg
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Toulouse
country: France
facility: Swedish Orphan Biovitrum Investigational Site
city: Berlin
country: Germany
facility: Swedish Orphan Biovitrum Investigational Site
city: Freiburg
country: Germany
facility: Swedish Orphan Biovitrum Investigational Site
city: Heidelberg
country: Germany
facility: Swedish Orphan Biovitrum Investigational Site
city: Wiesbaden
country: Germany
facility: Swedish Orphan Biovitrum Investigational Site
city: Budapest
country: Hungary
facility: Swedish Orphan Biovitrum Investigational Site
city: Gyula
country: Hungary
facility: Swedish Orphan Biovitrum Investigational Site
city: Miskolc
country: Hungary
facility: Swedish Orphan Biovitrum Investigational Site
city: Nyíregyháza
country: Hungary
facility: Swedish Orphan Biovitrum Investigational Site
city: Pécs
country: Hungary
facility: Swedish Orphan Biovitrum Investigational Site
city: Veszprem
country: Hungary
facility: Swedish Orphan Biovitrum Investigational Site
city: Ancona
country: Italy
facility: Swedish Orphan Biovitrum Investigational Site
city: Bari
country: Italy
facility: Swedish Orphan Biovitrum Investigational Site
city: Foggia
country: Italy
facility: Swedish Orphan Biovitrum Investigational Site
city: Milano
country: Italy
facility: Swedish Orphan Biovitrum Investigational Site
city: Padova
country: Italy
facility: Swedish Orphan Biovitrum Investigational Site
city: Roma
country: Italy
facility: Swedish Orphan Biovitrum Investigational Site
city: Bydgoszcz
country: Poland
facility: Swedish Orphan Biovitrum Investigational Site
city: Gdansk
country: Poland
facility: Swedish Orphan Biovitrum Investigational Site
city: Lodz
country: Poland
facility: Swedish Orphan Biovitrum Investigational Site
city: Poznan
country: Poland
facility: Swedish Orphan Biovitrum Investigational Site
city: Warszawa
country: Poland
facility: Swedish Orphan Biovitrum Investigational Site
city: Ivanovo
country: Russian Federation
facility: Swedish Orphan Biovitrum Investigational Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Swedish Orphan Biovitrum Investigational Site
city: Almería
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Cádiz
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Córdoba
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Madrid
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Málaga
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Oviedo
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Salamanca
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Santiago de Compostela
country: Spain
facility: Swedish Orphan Biovitrum Investigational Site
city: Stockholm
country: Sweden
facility: Swedish Orphan Biovitrum Investigational Site
city: Umeå
country: Sweden
facility: Swedish Orphan Biovitrum Investigational Site
Study officials:
affiliation: Swedish Orphan Biovitrum
name: Kristina Timdahl, MD
role: STUDY_DIRECTOR
References:
citation: Casper C, Hascoet JM, Ertl T, Gadzinowski JS, Carnielli V, Rigo J, Lapillonne A, Couce ML, Vagero M, Palmgren I, Timdahl K, Hernell O. Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study. PLoS One. 2016 May 31;11(5):e0156071. doi: 10.1371/journal.pone.0156071. eCollection 2016.
citation: Casper C, Carnielli VP, Hascoet JM, Lapillonne A, Maggio L, Timdahl K, Olsson B, Vagero M, Hernell O. rhBSSL improves growth and LCPUFA absorption in preterm infants fed formula or pasteurized breast milk. J Pediatr Gastroenterol Nutr. 2014 Jul;59(1):61-9. doi: 10.1097/MPG.0000000000000365.