Optimization of growth hormone dosing in children born small for gestational age: an open-label, randomized study of children during the fourth year of therapy

Background: Optimal dosage for growth hormone (GH) therapy in short, prepubertal children born small for gestational age (SGA) is controversial.

Methods: SGA OPTIMIS (NCT00249821) is a multicenter, open-label, parallel-group, pilot study of short children born SGA who had received recombinant human GH (r-hGH) (57 μg/kg/day) for 3 years. Children were randomized 1:1 to receive either 57 or 35 μg/kg/day r-hGH during year 4. The primary endpoint was height gain during year 4.

Results: 22 children were randomized (57 μg/kg/day, n = 10; 35 μg/kg/day, n = 12) and 21 completed the fourth year of therapy; 22 were included in efficacy analyses. During year 4, mean [standard deviation (SD)] height velocity was 6.4 (1.4) and 4.4 (1.2) cm/year (p = 0.001) and height velocity SD score (SDS) was 0.3 (0.3) and -0.1 (0.2) (p = 0.002) in the 57 and 35 μg/kg/day groups, respectively. The 57 μg/kg/day group continued with catch-up growth, had a significantly higher mean weight gain (p = 0.015) and significantly higher insulin-like growth factor-I levels at 12 months (p = 0.038). Five treatment-emergent adverse events were reported; none was serious or caused study withdrawal.

Conclusions: Children who continued receiving 57 μg/kg/day r-hGH in year 4 had significantly greater height gain than those receiving 35 μg/kg/day r-hGH.