, et al
PDA-TOLERATE trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age
J Pediatr.
; doi:

Investigators from multiple international institutions conducted a randomized controlled trial to compare the effectiveness of early routine treatment (ERT) of moderate to large patent ductus arteriosus (PDA) persisting beyond the first week of life to conservative treatment (CT) in premature infants. Study participants were recruited from 17 sites between 2014 and 2017 and met the following criteria: birth at ≥23 to <28 weeks’ gestation, age of 6–14 days, moderate to large PDA documented by means of echocardiography, and need for more than minimal respiratory support. Moderate to large PDA was defined as having an internal diameter of ≥1.5 mm, or a PDA left pulmonary artery diameter ratio of ≥0.5, and meeting other specific echocardiographic criteria. Neonates randomized to ERT were administered indomethacin, ibuprofen, or acetaminophen according to specific protocols. Those in the CT group were not initially administered pharmacologic agents to close their PDAs. Neonates in the CT group could be provided rescue pharmacologic treatment if they had a persistent moderate to large PDA and developed specific morbidities related to the PDA. Rescue treatment was also available for infants receiving ERT whose initial pharmacologic treatment was unsuccessful.

The primary study outcome was need for PDA ligation or cardiology follow-up for PDA after discharge. Secondary outcomes included occurrence of necrotizing enterocolitis, bronchopulmonary dysplasia, death, need for inotropic support, bacteremia not caused by coagulase-negative Staphylococcus, and duration of gavage feeding. Regression analyses were used to compare outcomes among infants in the ERT and CT groups; subgroup analyses were conducted in study patients born at ≥26 weeks’ gestation.

Data were analyzed in 202 infants: 104 in the ERT group and 98 in the CT group. Among those in the ERT group, 32% had PDA ligation or outpatient PDA follow-up compared to 39% of those randomized to CT (risk ratio [RR], 0.81; 95% CI, 0.55–1.2). There were also no statistically significant differences between groups for any of the secondary outcomes except that neonates in the ERT group were less likely than those in the CT group to receive inotropic support (RR, 0.53; 95% CI, 0.29–0.98). Among the subgroup of study patients born at ≥26 weeks’ gestation, 16% of those randomized to ERT died versus 2.1% of those in the CT group (RR, 7.7; 95% CI, 1.04–59.0). Infants in this subgroup receiving ERT were also significantly more likely than those randomized to CT to have bacteremia and required gavage feedings for a significantly longer duration.

The authors conclude than in newborns born at <28 weeks’ gestation, ERT for moderate to large PDA did not improve outcomes and was associated with higher risks of morbidity and mortality in those born at ≥26 weeks’ gestation.

Dr Mintzer has disclosed no financial relationship relevant to this commentary. This commentary does...

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