A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants

Abstract

Objective: Bronchopulmonary dysplasia (BPD) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities. Developing drugs for the prevention of BPD would improve public health. We sought to determine characteristics of favorable randomized controlled trials (RCTs) of drugs for BPD prevention.

Study design: We searched MEDLINE and EMBASE from 1992 to 2014 using the MeSH terms 'BPD' and 'respiratory distress syndrome, newborn'. We included a Cochrane Library search to ensure inclusion of all available RCTs. We identified RCTs with BPD as a primary or secondary outcome and determined the definition of BPD used by the study. We determined whether a phase I or phase II study-to determine drug safety, efficacy or optimal dose-was performed before the RCT. Finally, we searched the Cochrane Library for meta-analyses for each drug and used the results of available meta-analyses to define a favorable versus unfavorable RCT.

Result: We identified 2026 articles; 47 RCTs met our inclusion criteria encompassing 21 drugs; 5 of the drugs reduced the incidence of BPD. We found data from phase I or II studies for 16 of the drugs, but only 1 demonstrated a reduction of BPD.

Conclusion: The majority of the drugs studied in RCTs failed to reduce the incidence of BPD. Performing early-phase studies before phase III trials might provide necessary information on drugs and drug doses capable of preventing BPD, thus informing the development of future RCTs.

Figure 1

Results of the literature search and article selection for randomized controlled studies of drugs for the prevention of bronchopulmonary dysplasia in infants.