Pentoxifylline and Late Onset Sepsis in Preterm Infants

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

• 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.

Study Overview

• Status: Completed
• Conditions: Neonatal Late Onset Sepsis
• Intervention / Treatment: Drug: Pentoxifylline (PTX); Drug: Placebo

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Eldakahlia
    • Mansoura, Eldakahlia, Egypt, 35516
      • Mansoura University Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 days to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abd Elazeez Attala Shabaan
• Investigators: Principal Investigator: Abd Elazeez AT Shabaan, PhD, mansoura university, faculty of medicine

Publications and helpful links

General Publications

• Shabaan AE, Nasef N, Shouman B, Nour I, Mesbah A, Abdel-Hady H. Pentoxifylline therapy for late-onset sepsis in preterm infants: a randomized controlled trial. Pediatr Infect Dis J. 2015 Jun;34(6):e143-8. doi: 10.1097/INF.0000000000000698.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimate): June 13, 2014

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: June 12, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: randomized controlled trial; pentoxifylline; neonatal
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Toxemia; Neonatal Sepsis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: 12345 (Danish Center for Healthcare Improvements); R88 (Other Identifier: local institutional research board)