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Randomized Controlled Trial
. 2019 May;39(5):599-607.
doi: 10.1038/s41372-019-0347-4. Epub 2019 Mar 8.

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320)

Melissa Liebowitz  1 , Joseph Kaempf  2 , Omer Erdeve  3 , Ali Bulbul  4 , Stellan Håkansson  5 , Johanna Lindqvist  5 , Aijaz Farooqi  5 , Anup Katheria  6 , Jason Sauberan  6 , Jaideep Singh  7 , Kelly Nelson  7 , Andrea Wickremasinghe  8 , Lawrence Dong  8 , Denise C Hassinger  9 , Susan W Aucott  10 , Madoka Hayashi  10 , Anne Marie Heuchan  11 , William A Carey  12 , Matthew Derrick  13 , Ilene Sue Wolf  13 , Amy Kimball  14 , Meera Sankar  15 , Tina Leone  16 , Jorge Perez  17 , Arturo Serize  17 , Ronald I Clyman  18   19
Affiliations
Randomized Controlled Trial

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320)

Melissa Liebowitz et al. J Perinatol. 2019 May.

Abstract

Objective: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.

Methods: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).

Results: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)).

Conclusion: Indomethacin was more effective than acetaminophen in producing ductus constriction.

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Conflict of interest statement

Conflict of Interest: Neither the authors nor any of the individuals listed in the Acknowledgement section have any conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram of patient distribution and ductus outcomes among Conservative management and Drug treatment groups. No RX*: Thirty infants with a moderate-to-large PDA did not receive rescue treatment because they either did not meet the Rescue clinical criteria (n=17) or the clinical team chose not to treat them despite having met Rescue criteria (n=13) (see Methods). 26/30 (87%) constricted their ductus spontaneously by the time of discharge from the hospital. Note: among the 38 infants treated with Early Rx Ibuprofen 34 received a loading dose of 10 mg/kg followed by maintenance doses of 5 mg/kg. Four infants received 20 mg/kg loading and 10 mg/kg maintenance doses. Only one of the four (25%) infants in the high dose group had successful ductus constriction.
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References

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