MRI Contrast Agents Go Head-to-Head: Researchers Find Greater Morphologic Information and Lesion Enhancement with Bracco's MultiHance® (gadobenate dimeglumine) Injection, 529 mg/mL When Compared to Gadavist (gadobutrol injection)

Results of the MERIT Study1 Published Online by the American Journal of Neuroradiology

PRINCETON, N.J.--(BUSINESS WIRE)--Mar 7, 2012 - A new study shows that the use of gadobenate dimeglumine, the highest relaxivity gadolinium-based contrast agent (GBCA) available for central nervous system (CNS) magnetic resonance imaging (MRI), over a high concentration MRI contrast agent may improve clinicians' ability to visualize lesions of the brain.

Results of the MERIT Study, the latest in a series of intraindividual studies directly comparing MRI contrast agents within the same test subjects, are published online in the American Journal of Neuroradiology. The findings suggest that the higher relaxivity agent, gadobenate dimeglumine (MultiHance, Bracco Diagnostics Inc., Princeton, NJ) may be linked to greater signal intensity, better contrast enhancement, and better lesion conspicuity in MRI of the brain. The authors also conclude that high concentration does not provide the same benefit as high relaxivity in improving diagnostic performance.

In this large multicenter, randomized, double blind crossover intraindividual study, researchers compared MultiHance to Gadavist (Bayer Healthcare, Wayne, NJ). They concluded that MultiHance provided significantly greater morphologic information, lesion enhancement and contrast enhancement when compared to Gadavist, at equivalent doses for MRI of the brain. They also found no relevant benefit for the more highly concentrated Gadavist in terms of lesion conspicuity, visualization or sensitivity for detection.

The study's aim was to compare the two agents using a carefully controlled multicenter, double-blind, randomized, intraindividual crossover study design, in which each of the 114 patients received 0.1 mmol/kg doses of both agents in two identical MR imaging examinations. This study is of particular interest because Gadavist differs from other approved GBCAs in that it is formulated at double concentration (twice the concentration of gadolinium is present per unit volume). As of 2011, there have been no studies performed to compare the more highly concentrated Gadavist with the higher relaxivity agent MultiHance for MR imaging of brain tumors.

The authors stated that “two conclusions can be drawn from our findings. Firstly, it is clear that contrast agent concentration in the vial has no effect on imaging performance since injection of the more highly concentrated (1.0 mol/L) GBCA at 0.1 mmol/kg bodyweight provides no appreciable clinical advantage relative to published findings for conventional GBCAs at standard concentration (0.5 mol/L) when compared with gadobenate dimeglumine at an identical dose of 0.1 mmol/kg bodyweight. The lack of any appreciable benefit with gadobutrol can be ascribed to the fact that the SI during the interstitial phase (i.e. at post-injection acquisition times of 3-10 minutes as typically performed for brain tumor imaging) depends solely on the total amount of gadolinium in the lesion (i.e., the total number of gadolinium molecules) and its relaxivity rather than on the gadolinium solution concentration. Secondly, it is clear that higher r1 relaxivity is instrumental in improving diagnostic performance relative to that achievable with conventional GBCAs at equivalent dose.”

These conclusions support a literature review and simulation model, published last year, which concluded that most clinical trials to date have not found a benefit for higher concentration MR agents. Instead, it is the dose and relaxivity of a compound, not the concentration, which significantly influence signal intensity in MRI.2

Statistically significant (p<0.0001; all readers, all comparisons) results in favor of MultiHance were demonstrated for each individual diagnostic information endpoint used in the study, as well as for quantitative parameters linked to the contrast enhancement obtained with the two agents (contrast-to-noise ratio, [CNR] and lesion to brain ratio [LBR]), when a preference was expressed by the three independent blinded readers.

“The key importance of this study is that its results were similar to prior clinical investigations of this kind comparing Magnevist® (gadopentetate dimeglumine) to MultiHance3, and OmniscanTM (gadodiamide) to MultiHance4, so you now have three studies of this design demonstrating similar findings for contrast agents used for MRI,” said Dr. Alberto Spinazzi, Sr. Vice President, Worldwide Medical and Regulatory Affairs at Bracco Diagnostics Inc. “These results are consistent in showing some clear advantages relative to performance associated with using the highest relaxivity agent for CNS MRI, MultiHance, versus other GBCAs.”

Rigorously designed and conducted, the MERIT study powerfully compared the performance of the two agents. The two contrast injections were performed in a blinded and fully randomized manner with an interval of two to fourteen days between administrations, to avoid any carryover effects. Half of the patients received MultiHance for their first exam and the other half received Gadavist first. Imaging parameters and post-dose acquisition times were kept identical for the two exams of each patient. To maintain the study blind, each agent was administered by an independent drug dispensing person. Images were evaluated by three independent and experienced neuroradiologists, who were unaffiliated with the enrollment centers, and fully blinded to any clinical information about the patients and the agents used in the two exams. Image assessments were made in terms of diagnostic information (global diagnostic preference, lesion border delineation, definition of disease extent, visualization of lesion internal morphology, lesion contrast enhancement) and quantitative parameters (signal intensity [SI], CNR and LBR).

The findings of all 3 readers in global diagnostic preference were highly significant (p<0.0001) between the 2 agents. Readers 1, 2 and 3 reported global preference for MultiHance in 40.7%, 47.4%, and 43.0% of patients compared with 5.3%, 6.1% and 6.1% of patients for Gadavist, respectively. Similar highly significant preference was demonstrated for each individual diagnostic endpoint. Reader preference was based on superior contrast enhancement and better delineation of lesion and/or internal lesion structure.

“Bracco Diagnostics believes that MultiHance may improve the visualization of CNS disorders in MRI, and that relaxivity, not concentration, is what matters when it comes to improved image quality, noted Carlo Medici, president and chief executive officer of Bracco Diagnostics Inc. “We are pleased that this large-scale clinical investigation supported this. This concurrence of clinical evidence is an important criterion for clinicians when making evidence-based decisions.”

About MultiHance

Bracco received FDA approval to market MultiHance in the USA in November 2004. MultiHance is indicated for intravenous use in MRI of the central nervous system in adults and children over 2 years of age to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine and associated tissues.

MultiHance has features that distinguish it from other GBCAs. As reported in the FDA-approved prescribing information, unlike other available gadolinium contrast agents, MultiHance demonstrates weak and transient interactions with serum proteins, which result in a proton magnetic relaxivity that is approximately twice that of other gadolinium contrast agents available for sale in the U.S. for CNS imaging. The higher relaxivity of MultiHance may result in greater signal intensity enhancement and better contrast enhancement at equivalent dose for CNS imaging.

For more information and complete Prescribing Information, please go to www.multihanceusa.com or usa.braccoimaging.com.

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), Nuclear Medicine through radioactive tracers, and Gastrointestinal Endoscopy. The diagnostic imaging offer is completed by several medical devices and advanced administration systems for contrast imaging products in the fields of radiology.

The Company operates in over 90 markets worldwide, either directly or indirectly, through subsidiaries, joint ventures, licenses and distribution partnership agreements. With an 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 and compliances with a sustainable eco-friendly production, ecology friendly production. Manufacturing activities are located in Italy, Switzerland, Japan, China and Germany.

Bracco Imaging is an innovative Research and Development (R&D) player 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 Centres located in Italy, Switzerland and USA.

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.

 

 
-- The risk for NSF appears highest among patients with:

 

-- chronic, severe kidney disease (GFR <30 ml>2), or

 

-- acute kidney injury.

 

 
-- Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (e.g. age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.

 

 
-- For patients at highest risk for NSF, do not exceed the recommended MultiHance dose and allow a sufficient period of time for elimination of the drug from the body prior to re-administration [see Warnings and Precautions (5.1)]  

 

 

 

 

Anaphylactic and anaphylactoid reactions have been reported, involving cardiovascular, respiratory, and/or cutaneous manifestations ranging from mild to severe. The possibility of a reaction 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.

 Please see full Prescribing Information including boxed WARNING at usa.braccoimaging.com or www.multihanceUSA.com.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

1 Seidl Z, et al. Does Higher Gadolinium Concentration Play a Role in the Morphologic Assessment of Brain Tumors? Results of a Multicenter Intraindividual Crossover Comparison of Gadobutrol versus Gadobenate Dimeglumine (the MERIT Study). AJNR. Published online before print March 1, 2012, doi: 10.3174/ajnr.A3033.

2 Heiland S, Erb G, Ziegler S, Krix M. Where contrast agent concentration really matters- a comparison of CT and MRI. Invest Radiol. 2010;45:1-9.

3 Maravilla KR, Maldjian JA, Schmalfuss IM, et al. Contrast enhancement of central nervous system lesions: multicenter intraindividual crossover comparative study of two MR contrast agents. Radiology 2006; 240:389-400.

4 Rowley HA, et al. Contrast-enhanced MR imaging of brain lesions: a large-scale intraindividual crossover comparison of gadobenate dimeglumine versus gadodiamide. AJNR. 2008;29:1684-91.

All trademarks and registered trademarks are the property of their respective owners.

 

Contact: Bracco Diagnostics Inc.
Lakshmi Sundar, 609-514-2236
lakshmi.sundar@diag.bracco.com

 

 

Posted: March 2012

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