Increased Indomethacin Dosing for Persistent Patent Ductus Arteriosus in Preterm Infants: A Multicenter, Randomized, Controlled Trial

Priya Jegatheesan, Vlad Ianus, Basharat Buchh, Grace Yoon, Nancy Chorne, Audrey Ewig, Emil Lin, Scott Fields, Anita Moon-Grady, Terri Tacy, Jay M Milstein, Michael Schreiber, James Padbury, Ronald Clyman

Research output: Contribution to journalArticle

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Abstract

Objective: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. Study design: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. Results: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). Conclusion: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.

Original languageEnglish (US)
Pages (from-to)183-189
Number of pages7
JournalJournal of Pediatrics
Volume153
Issue number2
DOIs
StatePublished - Aug 2008

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Retinopathy of Prematurity
Patent Ductus Arteriosus
Premature Infants
Indomethacin
Randomized Controlled Trials
Odds Ratio
Confidence Intervals
Kidney
Incidence

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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Increased Indomethacin Dosing for Persistent Patent Ductus Arteriosus in Preterm Infants : A Multicenter, Randomized, Controlled Trial. / Jegatheesan, Priya; Ianus, Vlad; Buchh, Basharat; Yoon, Grace; Chorne, Nancy; Ewig, Audrey; Lin, Emil; Fields, Scott; Moon-Grady, Anita; Tacy, Terri; Milstein, Jay M; Schreiber, Michael; Padbury, James; Clyman, Ronald.

In: Journal of Pediatrics, Vol. 153, No. 2, 08.2008, p. 183-189.

Research output: Contribution to journalArticle

Jegatheesan, P, Ianus, V, Buchh, B, Yoon, G, Chorne, N, Ewig, A, Lin, E, Fields, S, Moon-Grady, A, Tacy, T, Milstein, JM, Schreiber, M, Padbury, J & Clyman, R 2008, 'Increased Indomethacin Dosing for Persistent Patent Ductus Arteriosus in Preterm Infants: A Multicenter, Randomized, Controlled Trial', Journal of Pediatrics, vol. 153, no. 2, pp. 183-189. https://doi.org/10.1016/j.jpeds.2008.01.031
Jegatheesan, Priya ; Ianus, Vlad ; Buchh, Basharat ; Yoon, Grace ; Chorne, Nancy ; Ewig, Audrey ; Lin, Emil ; Fields, Scott ; Moon-Grady, Anita ; Tacy, Terri ; Milstein, Jay M ; Schreiber, Michael ; Padbury, James ; Clyman, Ronald. / Increased Indomethacin Dosing for Persistent Patent Ductus Arteriosus in Preterm Infants : A Multicenter, Randomized, Controlled Trial. In: Journal of Pediatrics. 2008 ; Vol. 153, No. 2. pp. 183-189.
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abstract = "Objective: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. Study design: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. Results: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52{\%}; higher = 45{\%}, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6{\%}, higher = 19{\%}, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15{\%}, higher = 36{\%}, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). Conclusion: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.",
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AU - Ianus, Vlad

AU - Buchh, Basharat

AU - Yoon, Grace

AU - Chorne, Nancy

AU - Ewig, Audrey

AU - Lin, Emil

AU - Fields, Scott

AU - Moon-Grady, Anita

AU - Tacy, Terri

AU - Milstein, Jay M

AU - Schreiber, Michael

AU - Padbury, James

AU - Clyman, Ronald

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N2 - Objective: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. Study design: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. Results: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). Conclusion: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.

AB - Objective: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. Study design: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. Results: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). Conclusion: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.

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