Elsevier

The Journal of Pediatrics

Volume 134, Issue 2, February 1999, Pages 151-155
The Journal of Pediatrics

Do sick newborn infants benefit from participation in a randomized clinical trial?☆,☆☆

Presented in part at the 67th Annual Meeting of the Society for Pediatric Research, New Orleans, Louisiana, May 1-5, 1998.
https://doi.org/10.1016/S0022-3476(99)70428-2Get rights and content

Abstract

Background: Adult participants in randomized controlled trials often have better outcomes than patients who are eligible but not enrolled. Objective: To examine whether newborn infants who were allocated to placebo in an investigational drug trial had better outcomes than infants who were eligible but not randomized (eligible NR). Study design: During a randomized controlled trial of antithrombin therapy in premature infants with respiratory distress syndrome, data were collected prospectively on all 76 infants in the eligible NR group. Study outcomes were compared with those of all 61 infants who were randomized to placebo. The same exogenous surfactant was used in all patients. Results: In the placebo group the mean (SD) birth weight was 1201 (314) g, mean (SD) gestational age was 28.8 (2.3) weeks, and 51% were male. In infants in the eligible NR group, mean (SD) birth weight was 1141 (262) g, mean (SD) gestational age was 28.3 (2.3) weeks, and 58% were male; 57% of infants in both groups had been exposed to steroids before birth. The median duration of mechanical ventilation was reduced from 6.2 days in the eligible NR group to 4.8 days in the placebo group (P = .008). There was also a trend toward less frequent and less severe intraventricular hemorrhage in trial participants. Conclusions: These data are consistent with the hypothesis that sick newborn infants may benefit from participation in a randomized controlled trial. (J Pediatr 1999;134:151-5)

Section snippets

Selection of Patients

This study took place at McMaster University Medical Center from November 1992 to February 1996 in a 33-bed neonatal intensive care unit that serves a regional population of 1.8 million people. Approximately 1000 newborn infants are admitted annually, of whom 80% are born in the center; the remainder are referred from surrounding hospitals.

Premature infants were eligible for enrollment in a placebo-controlled trial of antithrombin therapy if they fulfilled all of the following inclusion

RESULTS

During the study period 224 infants were identified who met all inclusion criteria, 198 of whom had no exclusion criteria present and were thus eligible. One hundred twenty-two of these eligible subjects were randomized, 61 of them to placebo. The most frequent reason for not randomizing an eligible patient was lack of informed parental consent (n = 38); the families of 24 patients were not approached (usually because of an administrative oversight). Randomization was also suspended for a short

DISCUSSION

Premature infants with moderate to severe respiratory distress syndrome who were eligible but not randomized in a recent investigational drug trial of antithrombin therapy appeared to have worse immediate outcomes than infants who had been allocated to the placebo arm of the controlled trial. Although the results of any nonrandomized comparison must be interpreted with caution, the validity of our observation is enhanced by the close balance at baseline for most important prognostic factors in

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