A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia
- A R Bedford Russella,
- A J B Emmersonb,
- N Wilkinsona,
- T Chantb,
- D G Sweetc,
- H L Hallidayc,
- B Hollandd,
- E G Daviesa
- aSt George's Hospital, Blackshaw Rd, London SW17 0QT, UK, bSt Mary's Hospital for Women and Children, Whitworth Park, Manchester M13 0JH, UK, cRoyal Maternity Hospital, Belfast, Northern Ireland, dThe Queen Mother's Hospital, Glasgow, Scotland, UK
- Dr Bedford Russell, Neonatal Unit, St George's Hospital, Blackshaw Rd, London SW17 0QT, UKalison.bedford-russell{at}stgh-tr.sthames.nhs.uk
- Accepted 29 November 2000
Abstract
OBJECTIVES The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.
DESIGN Neonates (⩽ 28 days) in intensive care, with birth weights of 500–1500 g, absolute neutrophil count (ANC) of ⩽ 5 × 109/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 μg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.
RESULTS Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p ⩽ 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).
CONCLUSIONS In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.
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rhG-CSF increases the absolute neutrophil count in very low birthweight infants with neutropenia and sepsis
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Thrombocytopenia is not an effect of rhG-CSF treatment
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Potential beneficial effects on long term survival require further investigation
- neutropenia
- sepsis
- very low birthweight infants
- recombinant human granulocyte colony stimulating factor
- antibiotic use
- intensive care
