PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.
bronchopulmonary dysplasia; necrotizing enterocolitis; newborn; premature birth; retinopathy of prematurity
OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given.
STUDY DESIGN: A total of 202 neonates of(mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial.
RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%).
CONCLUSIONS: In preterm infants ageweek, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.
Women & Children
Clyman, Ronald I; Liebowitz, Melissa; Kaempf, Joseph; Erdeve, Omer; Bulbul, Ali; Håkansson, Stellan; Lindqvist, Johanna; Farooqi, Aijaz; Katheria, Anup; Sauberan, Jason; Singh, Jaideep; Nelson, Kelly; Wickremasinghe, Andrea; Dong, Lawrence; Hassinger, Denise C; Aucott, Susan W; Hayashi, Madoka; Heuchan, Anne Marie; Carey, William A; Derrick, Matthew; Fernandez, Erika; Sankar, Meera; Leone, Tina; Perez, Jorge; and Serize, Arturo, "PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age." (2018). Articles, Abstracts, and Reports. 764.