| Methods |
Multi‐centre randomised double‐blind placebo controlled trial |
| Participants |
28 infants with early or late onset sepsis.
Inclusion criteria were clinical signs of sepsis plus either neutropenia or proven bacteraemia.
Sepsis defined as one of: Shock (requiring fluid boluses, vasopressors, or developing acidosis), Respiratory failure requiring mechanical ventilation; Necrotising enterocolitis (radiological or surgical diagnosis).
Neutropenia defined as <1 x 10(9)/l
Neutropenia secondary to maternal preeclampsia was not counted as a criteria for recruitment .
GA < 32w, BW 445 ‐ 1960g, no postnatal age limit. |
| Interventions |
Randomisation was to G‐CSF, GM‐CSF or placebo.
10 infants received G‐CSF 10 mg/kg/day in 2 divided doses by iv inf.
10 infants received GM‐CSF 8 mg/kg/day in 2 divided doses by iv inf.
8 infants received placebo.
Treatment continued for 6 days, or until ANC > 10 x 10(9)/l.
G‐CSF (Filgrastim, Neupogen, Amgen, Thousand Oaks, CA)
GM‐CSF (Sargramostim, Leukine, Immunex, Seattle, WA)
Placebo was 2 ml saline. |
| Outcomes |
Mortality to discharge.
Neutrophil counts on days 2,5,7 from study entry.
* 3 infants died directly related to the septic episode: 2 G‐CSF; 1 GM‐CSF group. 1 additional infant who received G‐CSF died from a new infection 1 month later. |
| Notes |
12 infants had early onset sepsis (G‐CSF 2; GM‐CSF 4; Placebo 6)
16 infants had late onset sepsis (G‐CSF 8; GM‐CSF 6; Placebo 2)
Positive blood cultures at recruitment:11 Treated infants; of which Gram negs = 5.
5 Placebo infants; of which Gram negs = 1.
(Gram negs were E.coli (4) or Klebsiella sp (1). There were no GBS or Staph aureus isolates)
Outcome of infants with positive cultures not reported separately.
Number of infants with neutropenia at recruitment not reported, nor outcomes of neutropenic subgroup. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment? |
Unclear risk |
B ‐ Unclear |
