MONROE TOWNSHIP, NJ, December 3, 2019 — Bracco Diagnostics Inc., the U.S subsidiary of Bracco Imaging S.p.A., a leading global company in the diagnostic imaging business, announced the results of an experimental artificial intelligence (AI) study of two gadolinium-based contrast agents (GBCAs) which found that ProHance (Gadoteridol) Injection, 279.3 mg/mL and Gadavist provided similar degree and pattern of contrast enhancement in brain magnetic resonance imaging (MRI) of patients with glioblastoma multiforme (GBM) previously enrolled in a large scale, multicenter, randomized, double blinded controlled clinical study (the TRUTH study).1 Full study results will be presented at the Radiological Society of North America (RSNA) Annual Meeting on Wednesday, December 4, in Chicago, IL.
GBCAs are widely used imaging agents with a favorable safety profile. While recent research has shown that the gadolinium from these agents may remain in the body for months to years after injection,2 the American College of Radiology and the Food and Drug Administration agree that there are no known adverse clinical consequences associated with gadolinium retention in the brain based on the available data.3,4 Nevertheless, some practitioners have concerns, and questions have been raised over whether using a GBCA that retains less would come with a tradeoff in the effectiveness of the contrast enhancement. The purpose of this study was to use AI to determine the effectiveness of standard concentration ProHance (0.5mmol/ml) compared to double concentration Gadavist (1.0 mmol/ml), since animal studies have shown that Gadavist retains two to seven times more in the brain versus ProHance, at up to 4 weeks after injection5-6.
“We are pleased to share these innovative findings that not only help address an important question about gadolinium-based contrast agents, but also reinforce the results of the TRUTH study, which showed no significant difference in detection and characterization of central nervous system lesions with ProHance when compared to Gadavist7,” said Vittorio Puppo, President and CEO of Bracco Diagnostics Inc. “We believe the potential of cutting-edge technologies, like the ones developed by A.I. Analysis, Inc., will allow us continue to produce sophisticated research to help clinicians make optimal imaging decisions for their patients.”
About the Study
Each of the 32 patients with GBM in the study received both ProHance contrast and Gadavist contrast in a double-blind, randomized crossover technique. The images were evaluated in a blinded fashion using A.I. Analysis, Inc.’s Change Detector for Brain Imaging software, an advanced, layered machine-learning system.* Enhancement characteristics for both agents were processed and the differences for each set of image pairs were calculated and analyzed. A 90 percent confidence interval of the mean of the difference in enhancement was calculated with a zone of equivalence defined to be from -0.2 to +0.2.
In the 27 patients that were evaluable, the Change Detector software found no statistically significant difference in enhancement characteristics between the standard concentration of ProHance contrast and the double concentration of Gadavist contrast. The p-value from paired t-test was p=0.3126. The Pearson correlation coefficient between the normalized ProHance contrast and Gadavist contrast was 0.958 (p<0.0001). For all 27 image pairs, the 90 percent confidence intervals were within the zone of equivalence.
“We are pleased at these results, and look forward to continued partnerships with global imaging leaders like Bracco to glean new insights that can help better inform the radiology community,” said Dr. Matthew J. Kuhn, Chief Medical Officer at A.I. Analysis, Inc.
*The Change Detector for Brain Imaging software is an experimental machine learning software program which has not been approved by the FDA and it is not intended for clinical use at this time.
Indications and Usage for ProHance® (Gadoteridol) Injection, 279.3 mg/mL
CENTRAL NERVOUS SYSTEM
ProHance® (Gadoteridol) Injection, 279.3 mg/mL is indicated for use in MRI in adults and children over 2 years of age to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues.
ProHance (Gadoteridol) Injection, 279.3 mg/mL is indicated for use in MRI in adults to visualize lesions in the head and neck.
IMPORTANT SAFETY INFORMATION:
WARNING: NEPHROGENIC SYSTEMIC FIBROSIS
Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle and internal organs.
As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life threatening, or fatal, anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic disorders. Trace amounts of gadolinium may remain for months or years in the body organs including bone (highest concentration), brain, liver, spleen, kidneys and skin. Consequences of gadolinium retention in the brain have not been established. Pathologic and clinical consequences of retention in skin and other organs have been established in patients with impaired renal function. Minimize repetitive GBCA imaging studies, particularly close spaced studies when possible.
Please see full Prescribing Information and Patient Medication Guide for additional important safety information for/regarding ProHance (Gadoteridol) Injection, 279.3 mg/mL at https://imaging.bracco.com/us-en/products/magnetic-resonance-imaging/prohance
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/Safety/MedWatch/default.htm or call 1-800-FDA-1088.
ProHance is manufactured for Bracco Diagnostics Inc. by BIPSO GmbH – 78224 Singen (Germany).
ProHance is a registered trademark of Bracco Diagnostics Inc.
All other trademarks and registered trademarks are the property of their respective owners.
About Bracco Imaging
Bracco Imaging S.p.A., part of the Bracco Group, is one of the world’s leading companies in the diagnostic imaging business. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions that meet medical needs.
Bracco Imaging offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray Imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers. The diagnostic imaging portfolio is completed by a range of medical devices and advanced administration systems for contrast imaging products.
The company operates in over 100 markets worldwide, either directly or indirectly, through subsidiaries, joint ventures, licenses and distribution partnership agreements. With on-going research covering all key modalities, Bracco Imaging has a strong presence in key geographies: North America, Europe and Japan operating through the Joint Venture Bracco-Eisai Co. Ltd. The Company also operates in Brazil, South Korea, and China through the Joint Venture Bracco Sine Pharmaceutical Corp. Ltd.
Operational investments have been made in order to achieve top quality, compliant and sustainable eco-friendly production. Manufacturing activities are located in Italy, Switzerland, Japan, China, and Germany.
Bracco Imaging is an innovative Research and Development (R&D) structure with an efficient process-oriented approach and a track record of innovation in the diagnostic imaging industry. R&D activities are managed in the three Research Centers located in Italy, Switzerland, and the USA.
To learn more about Bracco Imaging, visit www.braccoimaging.com.
About A.I. Analysis, Inc.
AI Analysis, Inc has developed revolutionary patented machine learning processes which expertly manage the exponentially increasing volume of image data presented to radiologists for interpretation. Our system automatically and reproducibly provides the reader with highly curated, quantitative results, improving the accuracy and efficiency of radiological interpretations. The radiologist can have more time for consultations with patients and referrers and for advanced cognitive activities. In addition, we enable the precision use of decreased volumes of contrast media, and personalized medicine applications through our growing radiogenomics dashboard, all the while improving our patients’ health and welfare. (FDA application in preparation)
To learn more about A.I. Analysis, Inc. visit www.aianalysis.com.
Maravilla KR et al. Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). AJNR Am J Neuroradiol. 2015;36