Pentoxifylline and Late Onset Sepsis in Preterm Infants

Study Overview
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Brief Summary
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Hypothesis: The investigators hypothesized that Pentoxifylline has potent anti-inflammatory effect which can augment the antimicrobial effect of antibiotics in treatment of Late onset sepsis (LOS) in preterm infants thus decreasing neonatal mortality and morbidity. The purpose of this study: to assess the efficacy and safety of Pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity of preterm infants with LOS.

Detailed Description
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Role of pentoxifylline, a phosphodiesterase inhibitor, in reducing mortality associated with neonatal sepsis is not well studied. Hypothesis: we hypothesized that Pentoxifylline has potent anti-inflammatory effect which can augment the antimicrobial effect of antibiotics in treatment of Late onset sepsis (LOS) in preterm infants thus decreasing neonatal mortality and morbidity. Purpose of the study: to assess the efficacy and safety of Pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity of preterm infants with LOS. Design: A prospective, randomized, double-blind clinical trial. Setting: Neonatal Intensive Care Unit, Mansoura University Children's Hospital. Patients: 120 preterm infants with suspected or confirmed LOS. Intervention: Enrolled infants were randomly assigned to receive intravenous Pentoxifylline (5 mg/kg/hr for 6 hours on 6 successive days) or placebo in addition to antibiotics. Primary outcome: Death before hospital discharge. Secondary outcomes: Length of hospital stay, duration of respiratory support, duration of antibiotics use, chronic lung disease, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, Serum levels of Tumor necrosis factor, C-Reactive protein levels, and adverse effects of Pentoxifylline.

Official Title
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Pentoxifylline Therapy of Late-onset Sepsis in Preterm Infants: A Randomized Controlled Trial.

Conditions
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Neonatal Late Onset Sepsis

Intervention / Treatment
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* Drug: Pentoxifylline (PTX)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Appropriate for gestational age preterm infants with suspected or confirmed late onset sepsis Exclusion Criteria: Preterm infants with major congenital malformations Preterm infants with chromosomal anomalies Preterm infants with inborn-errors of metabolism Preterm infants with congenital infection

Ages Eligible for Study
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Minimum Age: 5 Days
Maximum Age: 7 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pentoxyfilline arm<br>Pentoxifylline 5 mg/kg/hr for 6 hours on 6 successive days in addition to antibiotics. | Drug: Pentoxifylline (PTX)<br>* Patients were randomly assigned to receive intravenous Pentoxifylline 5 mg/kg/hr for 6 hours on 6 successive days in addition to antibiotics<br>* Other names: Trental (brand name);|
| Placebo Comparator: Placebo arm<br>Intravenous saline as a Placebo 5 mg/kg/hr for 6 hours on 6 successive days in addition to antibiotics. | Drug: Placebo<br>* Patients were randomly assigned to receive intravenous normal saline 5 mg/kg/hr for 6 hours on 6 successive days as a placebo in addition to antibiotics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal mortality | Mortality before discharge from neonatal intensive care unit | Expected 10 weeks postnatal age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Duration of hospital admission (days) | Expected average of 8 weeks post natal age | 
| Duration of respiratory support | Duration of respiratory support including oxygen, Continuous Positive Airway Pressure, mechanical ventilation(days) | Expected 4 to 6 weeks postnatal age | 
| Duration of antibiotics use | Duration of treatment of sepsis including meningitis | Expected 3 to 5 weeks postnatal age | 
| Chronic lung disease | Need for oxygen by 36 weeks corrected gestational age | By 36 weeks corrected gestational age | 
| Necrotising enterocolitis | Bell clinical and radiological criteria | Expected 6 weeks | 
| Intraventricular haemorrhage | By cranial ultrasound grading | Expected 2 weeks | 
| Periventricular leukomalacia | By cranial ultrasound | Expected 8 weeks | 
| Retinopathy of prematurity | Ophthalmologist using Ret-Cam | Expected 8 weeks | 
| Serum levels of Tumor necrosis factor-α, C-Reactive protein |  | 6 days after intervention | 
| Adverse effects of Pentoxifylline | Adverse effects of Pentoxifylline such as feeding intolerance, thrombocytopenia and cholestasis. | Up to 10 days after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonatal, pentoxifylline, randomized controlled trial