PROGRAMS

A multicentre, randomised controlled trial of Prophylactic Granulocyte-Macrophage colony-stimulating factor (GM-CSF) to reduce Sepsis in preterm neonates

Trial started: 2000  Trial ended: 2012 

Summary

Objectives

To determine whether prophylactic granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces sepsis and improves survival and longer-term outcomes in very preterm, small-for-gestational-age infants at high risk of neutropenia.

Methods

A single-blind, multicentre randomised controlled trial conducted in 26 centres involving 280 infants born at ?31 weeks' gestation and below the 10th centile for birthweight. Infants were randomised within 72 hours of birth to receive either GM-CSF (10 ?g/kg/day subcutaneously for 5 days) or standard management. Outcomes were assessed during the neonatal period, with follow-up of surviving children at 2 and 5 years.

Outcome measures

Primary neonatal outcome: Sepsis-free survival to 14 days after trial entry.

Longer-term outcomes: At 2 years, neurodevelopment, general health and health and social care costs; at 5 years, neurodevelopment, general health and educational attainment.

Results

GM-CSF increased neutrophil counts significantly more rapidly during the first 11 days but did not improve sepsis-free survival. Sepsis-free survival occurred in 93 of 139 infants receiving GM-CSF and 105 of 141 infants receiving standard management (difference ?8%, 95% confidence interval ?18 to 3).

At 2 years, there were no significant differences in overall health outcomes or health and social care costs. Survival without severe disability occurred in 87 of 134 (65%) children in the GM-CSF group and 87 of 131 (66%) controls (risk ratio 1.0, 95% confidence interval 0.8 to 1.2). There was some evidence of poorer respiratory outcomes in the GM-CSF group.

At 5 years, there were no significant differences in cognitive, general health or educational outcomes. Mean mental processing composite scores were 94 (SD 16) in the GM-CSF group and 95 (SD 15) in the control group (mean difference ?1, 95% confidence interval ?6 to 4). The suggestion of poorer respiratory outcomes in the GM-CSF group at 2 years was also observed at 5 years.

Conclusions

Early postnatal prophylactic GM-CSF corrected neutropenia but did not reduce sepsis or improve survival and short-term outcomes. Follow-up at 2 and 5 years found no evidence of improved neurodevelopmental, general health or educational outcomes.

Summary based on:

Carr R, Brocklehurst P, Dore CJ, et al. Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial. Lancet. 2009;373(9659):226–233. https://doi.org/10.1016/S0140-6736(09)60071-4.