Nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates.
OBJECTIVE
To evaluate the efficacy and safety of nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates at high risk of bronchopulmonary dysplasia (BPD).


METHODS
Single-center, randomized, double-blind, placebo-controlled trial was conducted. Infants of 23(0) to 27(6) weeks' gestational age requiring mechanical ventilation or ≥30% supplemental oxygen on continuous positive airway pressure at 72-168 hours were randomized to receive 20 mg/kg (1 mL/kg) nebulized pentoxifylline or an equal volume of normal saline placebo every 6 hours for 10 consecutive days via a vibrating mesh nebulizer. The primary outcome was the duration of oxygen supplementation at 40 weeks' postmenstrual age. We used Cox proportional hazards regression modeling to analyze outcomes.


RESULTS
All infants had adequate data for analysis of the primary outcome. Intention-to-treat analysis revealed no differences in duration of oxygen supplementation at 40 weeks' postmenstrual age between pentoxifylline (n=41) and placebo (n=40) groups (median 2262 vs 2160 hours, adjusted hazard ratio: 1.14, 95% CI 0.72-1.80, P=.63). There was no difference in mortality and further secondary outcomes. No adverse effects were noted.


CONCLUSIONS
Nebulized pentoxifylline is safe but did not reduce the duration of oxygen supplementation in extremely preterm infants at high risk of BPD. Dose-ranging studies and large, well-designed clinical trials are required to determine whether the use of nebulized or systemic pentoxifylline as a prophylactic therapy offers small but relevant benefits for prevention of BPD.


BACKGROUND
Australian New Zealand Clinical Trials Registry: ACTRN12611000145909.
Centre for Neonatal Research and Education, The University of Western Australia, Crawley, Australia; University Children's Hospital Basel (UKBB), Basel, Switzerland. Electronic address: sven.schulzke@unibas.ch.
Sven M
SM
Schulzke
Centre for Neonatal Research and Education, The University of Western Australia, Crawley, Australia; Neonatal Clinical Care Unit, King Edward Memorial Hospital for Women, Subiaco, Australia.
Mangesh
M
Deshmukh
Women and Infants Research Foundation, Subiaco, Australia.
Elizabeth A
EA
Nathan
Women and Infants Research Foundation, Subiaco, Australia.
Dorota A
DA
Doherty
Centre for Neonatal Research and Education, The University of Western Australia, Crawley, Australia; Neonatal Clinical Care Unit, King Edward Memorial Hospital for Women, Subiaco, Australia.
Sanjay K
SK
Patole
D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D045422:Continuous Positive Airway Pressure; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D053208:Kaplan-Meier Estimate; D008297:Male; D010100:Oxygen / Q000008:administration & dosage*; D010431:Pentoxifylline / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012121:Respiration, Artificial; D013997:Time Factors
D010100:Oxygen; D010431:Pentoxifylline