Gadavist® (gadobutrol) injection Clinical Trial Data

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Gadavist® (gadobutrol) injection Clinical Trial Data

Efficacy in Clinical Trials - Central Nervous System (CNS)

Results for Gadavist® MRI of the Central Nervous System (CNS) Clinical Studies

Patients were enrolled in two clinical trials to evaluate three visualization parameters. The studies were designed to demonstrate superiority of Gadavist MRI to non-contrast MRI for lesion visualization. Pre-contrast and pre-plus-post contrast (paired images) were independently evaluated by three blinded readers. Gadavist provided a statistically significant improvement when averaged over the three readers.

Table 1: Visualization Endpoint Results of CNS Adult MRI Studies with 0.1 mmol/kg Gadavist

Endpoint Study A
Study B
Pre-contrast Paired Difference* Pre-contrast Paired Difference
Contrast Enhancement 0.97 2.26 1.29^ 0.93 2.86 1.94^
Border Delineation 1.98 2.58 0.60^ 1.92 2.94 1.02^
Internal Morphology 1.32 1.93 0.60^ 1.57 2.35 0.78^
Average # Lesions Detected 8.08 8.25 0.17** 2.65 2.97 0.32^^

* Difference of means = (paired mean) - (pre-contrast mean)
^^Met noninferiority margin of -0.35
** Did not meet noninferiority margin of -0.35

Table 2: Primary Endpoint Visualization Scoring System

Score Visualization Characteristics
Contrast Enhancement Border Delineation Internal Morphology
1 None None Poorly visible
2 Weak Moderate Moderately visible
3 Clear Clear but incomplete Sufficiently visible
4 Clear and bright Clear and complete N/A

Table 3: Primary Endpoint Visualization Categorical Improvement for Average Reader

  Study A
Study B
Endpoint Categorical Improvement Categorical Improvement
(Paired - Pre-Contrast) % (Paired - Pre-Contrast) %
  ≤0 >0 - <1 1 - <2 ≥2 ≤0 >0 - <1 1 - <2 ≥2
Contrast Enhancement 1 30 55 13 3 6 34 57
Border Delineation 7 73 18 1 5 38 51 5
Internal Morphology 4 79 17 0 5 61 33 1

For both studies, the improvement of visualization endpoints in paired Gadavist images compared to pre-contrast images resulted in improved assessment of normal and abnormal CNS anatomy.

Pediatric Patients

Two studies in 44 pediatrics patients age younger than 2 years and 135 pediatric patients age 2 to less than 18 years supported extrapolation of adult CNS efficacy findings. For example, comparing pre vs paired pre- and post-contrast images, investigators selected the best of four descriptors under the heading, "Visualization of lesion-internal morphology (lesion characterization) or homogeneity of vessel enhancement" for 27/44 (62% = pre) vs 43/44 (98% = paired) MR images from patients age 0 to less than 2 years and 106/135 (78% = pre) vs 108/135 (80% = paired) MR images from patients age 2 to less than 18 years.

The safety and effectiveness of Gadavist® have been established in pediatric patients born at 37 weeks gestation or later based on imaging and pharmacokinetic data in 138 patients ages 2 to 17 years and 44 patients ages 0 to less than 2 years and extrapolation from adult data. The frequency, type and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults. No dose adjustment according to age is necessary in pediatric patients. The safety and effectiveness of Gadavist® have not been established in premature infants.

Reference: 1. Gadavist [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2014.

Efficacy in Clinical Trials - Breast

The Within-patient Sensitivity of breast magnetic resonance (BMR) with Gadavist® was Superior to that of Unenhanced MRI

The lower bound of the 95% Confidence Interval (CI) for the difference in within-subject sensitivity ranged from 19% to 42% for Study 1 and from 12% to 27% for Study 2.

Bar graph showing results of Gadavist® Study 1 and Study 2.

Three additional readers in each study read X-ray mammography (XRM) alone. Based on this patient population, within-patient sensitivity randged from 68% to 73% and specificity in non-malignant breasts ranged from 86% to 94% for these readers over both studies. The false positive detection rates for Gadavist® BMR ranged from 39% to 53% (95% CI Upper Bounds ranged from 44% to 58%).¹

Reference: 1. Gadavist [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2014.



Gadavist® (gadobutrol) injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI):

  • To detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system in adult and pediatric patients including term neonates.
  • To assess the presence and extent of malignant breast disease in adult patients.
  • To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).

Gadavist® is indicated for use in magnetic resonance angiography (MRA):

  • To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates.



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 fibrosis affecting the skin, muscle and internal organs.

  • The risk of NSF appears highest among patients with:
    • - Chronic, severe kidney disease (GFR <30 mL/min/1.73m2), 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 (for example, 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 GADAVIST dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.

Contraindication and Important Information about Hypersensitivity Reactions: Gadavist® is contraindicated in patients with history of severe hypersensitivity reactions to Gadavist®. Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist® administration. Before Gadavist® administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to Gadavist®.

Gadolinium Retention: Gadolinium is retained for months or years in several organs. Linear GBCAs cause more retention than macrocyclic GBCAs. At equivalent doses, retention varies among the linear agents. Retention is lowest and similar among the macrocyclic GBCAs. Consequences of gadolinium retention in the brain have not been established, but they have been established in the skin and other organs in patients with impaired renal function. While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Consider the retention characteristics of the agent and minimize repetitive GBCA studies, when possible.

Acute Kidney Injury: In patients with chronic renal impairment, acute kidney injury sometimes requiring dialysis has been observed with the use of GBCAs. Do not exceed the recommended dose in these patients.

Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of Gadavist®. Extravasation into tissues during Gadavist® administration may result in moderate irritation.

Overestimation of Extent of Malignant Disease in MRI of the Breast: Gadavist® MRI of the breast overestimated the histologically confirmed extent of malignancy in the diseased breast in up to 50% of the patients.

Low Sensitivity for Significant Arterial Stenosis: The performance of Gadavist® MRA for detecting arterial segments with significant stenosis (>50% renal, >70% supra-aortic) has not been shown to exceed 55%. Therefore, a negative MRA study alone should not be used to rule out significant stenosis.

Adverse Reactions: The most frequent (≥0.5%) adverse reactions associated with Gadavist® in clinical studies were headache (1.7%), nausea (1.2%) and dizziness (0.5%).

Please see Full Prescribing Information for Gadavist® (Vials and Syringes).

Please see Full Prescribing Information for Gadavist®(Pharmacy Bulk Package).

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