Intravenous pentoxifylline as adjunct therapy in preterm infants with late-onset sepsis or necrotizing enterocolitis

Pharmacokinetics of intravenous pentoxifylline as adjunct therapy in preterm infants with late-onset sepsis or necrotizing enterocolitis

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12616000219482

Enrollment

Registered

2016-02-18

Start date

2016-04-06

Completion date

2016-12-09

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

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 will enrol and consent 23 preterm infants (<29 weeks gestational age) and intravenously administer Pentoxifylline, adjunct to standard care, for 48hrs within 6 hours of the onset of symptoms suggestive of sepsis or NEC. After 48 hours treatment will cease if diagnosis is refuted or will continue for 4 days if diagnosis is proven. To measure the pharmacokinetic profile of Pentoxifylline a series of four small blood samples will be taken prior to starting treatment and during treatment. The pharmacokinetic profile will allow us to model the optimal infusion frequency and duration, which will be used as a guideline in larger randomised controlled trials that will assess white matter injury and long-term disability.

Interventions

Within 6 hours of onset of suspected late-onset sepsis or NEC patients will receive Pentoxifylline intravenous infusion 1ml/kg/h for 12h/day (60mg/kg/day) for 2 days followed by 1ml/kg/h for 6hr/day (30mg/kg/day) for 4 days if NEC or sepsis diagnosis is confirmed.

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

72 Hours to 6 Months

Healthy volunteers

Inclusion criteria

Gestation less than 32 weeks at birth and greater than 72 hours since birth Less than 6 hours from the onset of symptoms suggestive of late-onset sepsis or NEC Informed parental consent

Exclusion criteria

Congenital malformations Chromosomal abnormalities

Outcome results