FDA approval of Definity (perflutren lipid microsphere) for pediatric patients with suboptimal echocardiograms

This approval represents a significant step forward in pediatric medicine, providing healthcare professionals with a valuable tool to opacify the left ventricular chamber and better identify the left ventricular endocardial border. Currently, Definity is the most utilized, extensively studied, and a trusted diagnostic ultrasound enhancing agent in the U.S.

The FDA decision in March 2024 was based on usage data from three pediatric clinical trials conducted with Definity: the Golding study, which evaluated 40 patients, ranging from 1 month to 17 years of age, with significant cardiovascular disorders, including heart transplant, Kawasaki disease or congenital cardiovascular anomaly; the Fine study, which evaluated 36 patients, ranging from 10 to 21 years of age, who had previously undergone a heart transplant; and the Kutty study, a retrospective medical record review of 113 pediatric patients, ranging from 5 to 21 years, who had a diagnosis of known congenital or acquired heart disease or suspected cardiac disease.

These studies evaluated the use of Definity in a total of 189 patients (107 (56.5%) were male and 82 (43.5%) were female).

The Golding study, together with supportive data from the Fine and Kutty studies, demonstrate that left ventricular opacification with Definity (cumulative doses ranging from 6 µL/kg to 20 µL/kg) is successful in pediatric patients and that ultrasound contrast provides important information to guide management in such patients. In the Golding study, both the ability to detect wall motion abnormalities and the ability to perform ejection fraction determinations were improved in the majority (70% and 80%, respectively) of subjects. The Kutty and Fine studies each reported successful left ventricular opacification in all participants. In the Kutty study, wall motion and/or myocardial perfusion wall motion abnormalities were identified in 13 (11.5%) of the patients (all identified during stress testing), and the number of left ventricular segments visualized improved from 13 ± 1 per patient without contrast to 16 ± 1 segments per patient with contrast across all patients. The Fine study identified regional wall motion abnormalities detected in three patients (8.3%, n=36), and demonstrated successful myocardial perfusion imaging in 32 patients (88.9%), with imaging in some patients complicated by movement and/or insufficient heart rate factors.

All reported adverse events across all trials were mild, brief and reversible without intervention. Specifically, the Golding study reported no AEs among study participants; the Fine study reported that 33% of patients experienced mild AEs (palpitations, headache, nausea and shortness of breath) attributed to stress test procedures and not as a result of DEFINITY administration; and the Kutty study reported 11% of patients experienced AEs with no differences between Definity and those patients who did not receive Definity in frequencies of adverse events (chest/back/neck pain, headache, fatigue, dizziness, shortness of breath).