Le Bonheur Trial: Intravenous Indomethacin More Effective for hsPDAs

Intravenous indomethacin is more effective than intravenous acetaminophen in treating hemodynamically significant PDAs (hsPDAs) in very low birth weight (VLBW) infants, according to new Le Bonheur neonatology research published in the Journal of Perinatology.

Le Bonheur neonatologists, led by Jennifer M. Davidson, DO, conducted a randomized trial for the treatment of hsPDAs in very low birth weight (VLBW) infants. Echocardiogram criteria before and after treatment showed that IV indomethacin was more effective.

“We have several options for PDA closure in these very low birth weight infants with varying levels of effectiveness including intervention by medication therapies,” said Davidson.

Commonly used medical therapies are indomethacin and ibuprofen, but these have variable success and notable side effects. Surgical PDA ligation and transcatheter PDA closure can be used if medical therapies fail to close the PDA, but each comes with risks and lack of access for some hospitals. Studies have shown that, for some neonates, acetaminophen may be equally effective for treating hsPDAs with minimal side effects. Le Bonheur neonatologists wanted to examine this option of IV acetaminophen for treating hsPDA in VLBW infants.

To be included in the trial, infants met specific criteria including gestational age at birth between 22 and 32 weeks, birth weight less than 1500 grams, 21 days of age or younger and no previous pharmacologic treatment for PDA. Infants also had to meet strict echocardiogram criteria including left to right ductal flow and two out of three of the following: ductal size greater than or equal to 1.5 mm at smallest diameter, reversal of flow in descending aorta or left atrial size to aortic root ratio greater than or equal to 1.5.

Seventeen infants received 15 mg/kg dose of IV acetaminophen every six hours for 12 doses. Twenty infants received three doses of IV indomethacin every 12 hours with the amount of medication based on age. Each infant had a follow-up echocardiogram within seven days of the initiation of treatment. Successful PDA treatment was defined as no longer meeting the echocardiogram inclusion criteria for hsPDA. Results of the study showed that IV indomethacin was more effective in successful treatment of hsPDA. The rate of successful PDA closure was 55% when using IV indomethacin and 6% when using IV acetaminophen.

“Through our study of very low birth weight infants, we were unable to show successful treatment of hsPDA with IV acetaminophen when compared to IV indomethacin in preterm infants born prior to 32 weeks,” said Davidson. “In addition, many of our babies in the study treated with acetaminophen required interventional closure later on.”

If acetaminophen continues to be used as a primary treatment of hsPDA, future studies should include a different dosing strategy or route of administration to learn more about its efficacy in PDA closure.

Davidson JM, Ferguson J, Ivey E, Philip R, Weems MF, Talati AJ. A randomized trial of intravenous acetaminophen versus indomethacin for treatment of hemodynamically significant PDAs in VLBW infants [published online ahead of print, 2020 May 21]. J Perinatol. 2020;10.1038/s41372-020-0694-1. doi:10.1038/s41372-020-0694-1