ICUS Files Landmark FDA Petitions Seeking Expanded Use of Contrast-Enhanced Ultrasound and Removal of Outdated “Black Box” Warnings

Medical society says patients deserve broader access to a safe, affordable imaging option

CHICAGO--(BUSINESS WIRE)--The International Contrast Ultrasound Society (ICUS) announced today that it filed two Citizen Petitions with the U.S. Food and Drug Administration (FDA) urging the agency to expand approved uses of contrast-enhanced ultrasound (CEUS) and to modernize its regulation.

The first petition calls on the FDA to approve a whole-body indication for approved microbubble ultrasound contrast agents, replacing the traditional organ-by-organ approval approach. The second petition requests removal of the boxed warnings, commonly known as “black box” warnings, from the labels of the three FDA-approved ultrasound contrast agents: Definity^®, Lumason^®, and Optison^®.

ICUS, a nonprofit medical society dedicated to advancing the safe and appropriate use of contrast-enhanced ultrasound (CEUS) worldwide, said both petitions are grounded in extensive scientific literature, contemporary safety data and decades of clinical experience.

“Contrast-enhanced ultrasound has evolved dramatically over the past two decades, and our petitions provide strong evidence supporting the updating of regulations so they keep pace with science and clinical practice,” said Dr. Steven Feinstein, Co-President of ICUS.

Dr. Feinstein noted that current approvals of ultrasound contrast agent are limited to the heart and liver, but a large and compelling body of scientific literature, clinical practice guidelines and professional experience convincingly shows that these agents are exceptionally safe and effective for use in enhancing ultrasound images of organs throughout the body - including the kidneys, pancreas, spleen, bowel, thyroid, breast and reproductive organs.

“Ultrasound contrast agents are systemic agents, and limited organ-specific approvals are clinically illogical,” said Dr. Stephanie Wilson, Co-President of ICUS and Clinical Professor of Radiology and Gastroenterology at the University of Calgary.

“A whole-body indication would allow physicians to follow disease wherever it appears, using the same contrast agent and the same ultrasound examination,” Dr. Wilson said.

“The current limited approvals have the effect of discouraging broader adoption of CEUS and depressing patient access to a safe, affordable imaging option that can improve outcomes and save lives,” she said.

The second Citizen Petition urges the FDA to remove boxed warnings that have appeared on ultrasound contrast agent labels since 2007, and to move the remaining warnings to the “Warnings and Precautions” section of each label. ICUS argues that the boxed warnings were implemented at a time when significantly less safety information was available and that extensive safety data accumulated since then demonstrate that ultrasound contrast agents have an exceptionally favorable safety profile and risk-benefit ratio.

The petition notes that serious adverse reactions associated with ultrasound contrast agents are exceedingly rare and that safety studies involving millions of patients have now consistently shown a very low incidence of severe complications. ICUS further argues that the risks associated with ultrasound contrast agents compare favorably with those of contrast agents used in CT and MRI examinations, which do not carry boxed warnings.

“The black box no longer reflects the current state of the science,” said Dr, Jordan Strom, an ICUS board member and lead author of recent landmark safety studies. Dr. Strom is an Associate Professor of Medicine at Harvard Medical School, Director of the Echocardiography Laboratory at Beth Israel Deaconess Medical Center in Boston, Massachusetts, and Co-Director for the Center for Clinical Outcomes Research at the Richard A. and Susan F. Smith Institute for Evidence, Innovation, and Policy.

“When a warning exaggerates risk, it distorts vital information on which health care decisions are made,” Dr. Strom said.

ICUS also notes that numerous professional medical organizations have previously expressed support for removing the boxed warnings, citing the growing body of evidence demonstrating the safety and clinical value of CEUS.

“The FDA has an opportunity to bring regulation into line with modern medicine,” said Dr. Richard Barr, an ICUS board member, professor of radiology at Northeast Ohio Medical University, and editor-in-chief of Journal of Ultrasound in Medicine.

“These changes would improve access to high-quality imaging, particularly for patients with kidney disease, pregnant women and others who cannot safely undergo CT or MR examinations – or who cannot afford the higher cost of CT and MR,” Dr. Barr said.

Dr. Barr noted that training opportunities for “off-label” uses are severely limited, which in turn limits adoption. However, he said that off-label CEUS is supported by national and international clinical guidelines, and is reimbursed by Medicare and many private payors.

Contrast-enhanced ultrasound uses tiny gas-filled microbubbles that are administered intravenously during an ultrasound examination to improve visualization of blood flow and tissue perfusion. CEUS can be performed at the bedside, does not expose patients to ionizing radiation and does not utilize iodinated or gadolinium-based contrast agents.

About ICUS

The International Contrast Ultrasound Society (ICUS) is a nonprofit medical society dedicated to advancing the safe and medically appropriate use of contrast-enhanced ultrasound (CEUS) to improve patient care globally. ICUS membership is free, and there is no charge for the organization’s CME-accredited webinars, newsletters and CEUS resources. To learn more, visit www.icus-society.org.