Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2)
Condition: Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Retinopathy of Prematurity; Bronchopulmonary Dysplasia (BPD)
MeSH terms: Bronchopulmonary Dysplasia; Retinopathy of Prematurity; Premature Birth; Birth Weight
Intervention: Inositol lower volume; Inositol mid-level volume; Inositol high volume; Placebo low volume
Intervention description: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes; 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes; 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes; Glucose 5% given in volumes equal to that of the comparator drug
Intervention MeSH terms: Inositol
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 125.0
Sex: All
Minimum age: 12 Hours
Maximum age: 72 Hours
Healthy volunteers: Accepts Healthy Volunteers
Keywords: NICHD Neonatal Research Network; Pharmacokinetics; Inositol; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Prematurity

Summary:

      This pilot study is a randomized, placebo-controlled, clinical trial to measure changes in
      blood and urine levels of inositol in premature infants at high risk for retinopathy of
      prematurity (ROP) following repeated doses of inositol. Based on previous studies, the
      premise is that maintaining inositol concentrations similar to those occurring naturally in
      utero will reduce the rates of ROP and bronchopulmonary dysplasia in premature infants. The
      objective is to evaluate pharmacokinetics, safety, and clinical outcomes of multiple doses of
      three different dose amounts of myo-inositol (provided by Abbott Laboratories) in very low
      birth weight premature infants. This study will enroll an estimated 96 infants at 17 NICHD
      Neonatal Research Network sites. Infants will be randomly assigned to receive either 10 mg/kg
      of 5% inositol, 40 mg/kg of 5% inositol, 80 mg/kg of 5% inositol, or 5% glucose given in the
      same volumes and timings as the inositol dosage to maintain masking. Enrollees will receive
      their assigned dose or placebo daily, starting within 72 hours of birth, and continuing until
      they reach 34 weeks post-menstrual age, 10 weeks chronologic age, or until the time of
      hospital discharge, whichever occurs first. The study drug will be administered first
      intravenously; as the infants progress to full feeding, the drug will be given enterally
      (orally or via feeding tube). Enrollees will be seen for a follow-up examination at 18-22
      months corrected age. This pilot study is in preparation for a future Phase III multi-center
      randomized controlled trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  23 0/7 to 26 6/7 weeks gestational age (48 infants) or

          -  27 0/7 to 29 6/7 weeks gestational age (48 infants)

          -  401 grams birth weight or larger

          -  12-72 hours of age

        Exclusion Criteria:

          -  Major congenital and intracranial anomalies

          -  Moribund or not to be provided continued support

          -  Seizures

          -  Suspected renal failure (oliguria <0.6 cc/kg/hr for >24 hours or creatinine >2.5
             mg/dL)