Intravenous pentoxifylline as adjunct therapy to improve long-term disability in preterm infants

Preterm infants are highly susceptible to bacterial late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), both are major causes of systemic inflammation and contribute to brain injury and long-term disability in premature infants. Treating LOS and NEC are essential for survival, but suppressing systemic inflammation can also help reduce mortality, hospital stay and disability due to brain injury. The current treatments for NEC and LOS are limited to antibiotics, supportive care and surgery in some NEC cases, all of which do not aid in reducing systemic inflammation, therefore there is a need to reduce systemic inflammation. Pentoxifylline is a safe, low-cost, non-steroidal drug with potent immune-modulating activity with the potential of suppressing systemic inflammation induced by LOS or NEC. A recent Cochrane Review of 6 randomised controlled trials (RCT) suggests that PTX, given with antibiotics in neonatal sepsis, reduces mortality and length of hospital stay. We are conducting an international multicentre trial that will enrol and consent approximately 1,800 preterm infants (born <29 weeks gestational age). The primary aim is to evaluate the effect of treatment with intravenous Pentoxifylline versus placebo, starting within 6 hours from blood culture taken for suspected LOS or NEC. After 48 hours treatment will cease if diagnosis is refuted or will continue for 4 days if diagnosis is proven. The primary outcome to measure effectiveness is survival without disability at 18-24 months of age (corrected for gestation).