Pharmacotherapeutic group: Paramagnetic contrast media, ATC code: V08C A09
Mechanism of action
The contrast-enhancing effect is mediated by gadobutrol, the nonionic complex consisting of gadolinium(III) and the macrocyclic ligand dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol).
Pharmacodynamic effects
In clinical doses, gadobutrol leads to shortening of the relaxation times of protons in tissue water. At 0.47T (20MHz), pH7 and 40°C the paramagnetic effect (relaxivity), as determined from the effect on spin-lattice relaxation time (T1) measured in plasma - is about 5.6l mmol-1 sec-1 and the spin-spin relaxation time (T2) is about 6.5lmmol-1sec-1. Within the range 0.47 to 2.0Tesla, the relaxivity displays only slight dependency on the strength of the magnetic field.
Gadobutrol does not cross an intact blood-brain barrier and therefore does not accumulate in healthy brain tissue or in lesions featuring an intact blood-brain barrier. With high local tissue concentrations of gadobutrol the T2 effect results in a lessening of signal intensity.
Clinical efficacy
In a pivotal phase III liver study average sensitivity in combined pre and postcontrast MRI for Gadovist-treated patients was 79% and specificity was 81% for lesion detection and classification of suspected malignant liver lesions (patientbased analysis).
In a pivotal phase III kidney study average sensitivity was 91% (patient-based analysis) and 85% (lesion-based analysis) for classification of malignant and benign renal lesions. Average specificity in a patient-based analysis was 52% and in a lesion-based analysis 82%.
The increase of sensitivity from precontrast to combined pre and postcontrast MRI for Gadovist-treated patients was 33% in the liver study (patient-based analysis) and 18% in the kidney study (patient-based analysis as well as lesion-based analysis). The increase in specificity from precontrast to combined pre and postcontrast MRI was 9% in the liver study (patient based analysis) while there was no increase in specificity in the kidney study (patient-based analysis as well as lesion-based analysis).
All results are average results obtained in blinded reader studies.
In a study designed as an intra-individual, crossover comparison, Gadovist was compared to gadoterate meglumine (both at 0.1mmol/kg) in the visualization of cerebral neoplastic enhancing lesions in 132patients.
The primary efficacy endpoint was the overall preference for either Gadovist or gadoterate meglumine by the median blinded reader. Superiority of Gadovist was demonstrated by a p-value of 0.0004. In detail, a preference of Gadovist was given for 42patients (32%) compared to an overall preference for gadoterate meglumine for 16patients (12%). For 74patients (56%) no preference for one or the other contrast agent was given.
For the secondary variables lesion-to-brain ratio was found to be statistically significantly higher for Gadovist (p<0.0003). Percent of enhancement was higher with Gadovist compared to gadoterate meglumine, with a statistical significant difference for the blinded reader (p<0.0003).
Contrast-to-noise ratio, showed a higher mean value following Gadovist (129) compared to gadoterate meglumine (98). The difference was not statistically significant.
Paediatric population
Two single dose phase I/III studies in 138subjects scheduled for CE-MRI of CNS, liver and kidneys or CE-MRA and in 44subjects aged 0-<2years (including term neonates) scheduled to undergo routine CE-MRI of any body region have been performed. Diagnostic efficacy and an increase in diagnostic confidence was demonstrated for all parameters evaluated in the studies and there was no difference among the paediatric age groups and when compared to adults. Gadovist was well tolerated in these studies with the same safety profile of gadobutrol as in adults.
Pharmacotherapeutic group: Paramagnetic contrast media, ATC code: V08C A09
Mechanism of action
The contrast-enhancing effect is mediated by gadobutrol, the nonionic complex consisting of gadolinium(III) and the macrocyclic ligand dihydroxy-hydroxymethylpropyl-tetraazacyclododecane-triacetic acid (butrol).
Pharmacodynamic effects
In clinical doses, gadobutrol leads to shortening of the relaxation times of protons in tissue water. At 0.47T (20MHz), pH7 and 40°C the paramagnetic effect (relaxivity), as determined from the effect on spin-lattice relaxation time (T1) measured in plasma - is about 5.6l mmol-1 sec-1 and the spin-spin relaxation time (T2) is about 6.5lmmol-1sec-1. Within the range 0.47 to 2.0Tesla, the relaxivity displays only slight dependency on the strength of the magnetic field.
With high local tissue concentrations of gadobutrol the T2 effect results in a lessening of signal intensity.
Clinical efficacy
In a pivotal phase III liver study average sensitivity in combined pre and postcontrast MRI for Gadovist-treated patients was 79% and specificity was 81% for lesion detection and classification of suspected malignant liver lesions (patientbased analysis).
In a pivotal phase III kidney study average sensitivity was 91% (patient-based analysis) and 85% (lesion-based analysis) for classification of malignant and benign renal lesions. Average specificity in a patient-based analysis was 52% and in a lesion-based analysis 82%.
The increase of sensitivity from precontrast to combined pre and postcontrast MRI for Gadovist-treated patients was 33% in the liver study (patient-based analysis) and 18% in the kidney study (patient-based analysis as well as lesion-based analysis). The increase in specificity from precontrast to combined pre and postcontrast MRI was 9% in the liver study (patient based analysis) while there was no increase in specificity in the kidney study (patient-based analysis as well as lesion-based analysis).
All results are average results obtained in blinded reader studies.
In a study designed as an intra-individual, crossover comparison, Gadovist was compared to gadoterate meglumine (both at 0.1mmol/kg) in the visualization of cerebral neoplastic enhancing lesions in 132patients.
The primary efficacy endpoint was the overall preference for either Gadovist or gadoterate meglumine by the median blinded reader. Superiority of Gadovist was demonstrated by a p-value of 0.0004. In detail, a preference of Gadovist was given for 42patients (32%) compared to an overall preference for gadoterate meglumine for 16patients (12%). For 74patients (56%) no preference for one or the other contrast agent was given.
For the secondary variables lesion-to-brain ratio was found to be statistically significantly higher for Gadovist (p<0.0003). Percent of enhancement was higher with Gadovist compared to gadoterate meglumine, with a statistical significant difference for the blinded reader (p<0.0003).
Contrast-to-noise ratio, showed a higher mean value following Gadovist (129) compared to gadoterate meglumine (98). The difference was not statistically significant.
Paediatric population
Two single dose phase I/III studies in 138subjects scheduled for CE-MRI of CNS, liver and kidneys or CE-MRA and in 44subjects aged 0-<2years (including term neonates) scheduled to undergo routine CE-MRI of any body region have been performed. Diagnostic efficacy and an increase in diagnostic confidence was demonstrated for all parameters evaluated in the studies and there was no difference among the paediatric age groups and when compared to adults. Gadovist was well tolerated in these studies with the same safety profile of gadobutrol as in adults.