Efficacy and safety of gadodiamide (Gd-DTPA-BMA) in renal 3D-magnetic resonance angiography (MRA): a phase II study.
OBJECTIVE
To determine the most efficacious dose of gadodiamide for three-dimensional (3D) contrast-enhanced (CE) magnetic resonance angiography (MRA) of the renal arteries on a patient level based on the sensitivity in detecting the main hemodynamically relevant (> or =50% or occlusion) renal artery stenosis (RAS) using intra-arterial digital subtraction angiography (IA DSA) as the gold standard.


METHODS
This prospective, randomized, double-blind, parallel-group, multicenter study included 273 patients referred to IA DSA for suspected RAS. Patients underwent 3D CE MRA after injection of 0.01, 0.05, 0.1, or 0.2mmol/kg of body weight gadodiamide (0.5mmol/ml). The images were assessed for location and degree of RAS by independent blinded readers (MRA: three readers, IA DSA: one reader). Hypothesis testing for a significant trend in sensitivity across dose groups was based on the one-sided Cochran-Armitage style trend test for each independent MRA reader.


RESULTS
The lowest dose group (0.01mmol/kg) proved non-efficacious in detecting hemodynamically relevant (i.e., > or =50% or occlusion) RAS. A statistically significant dose trend (p<0.001) was shown for each of the three independent readers. Depending on reader, the sensitivity obtained with 0.05, 0.1, and 0.2mmol/kg was 63.9-86.1%, 75.8-91.4% and 80.6-90.6%, the specificity was 66.7-73.9%, 59.3-75.0%, and 59.3-75.0% and accuracy was 67.8-78.9%, 75.4-77.4%, and 76.3-81.0%, for the three dose groups, respectively. There were eight non-severe adverse events (AEs). Three serious AEs occurring in one patient were judged not related to gadodiamide by the on-site investigator.


CONCLUSIONS
A significant dose trend between the four doses examined was observed. The lowest dose (0.01mmol/kg) differed significantly from those of the other three doses. Based on the analysis of the primary and secondary endpoints, 0.1mmol/kg gadodiamide appears to be the most suitable dose in diagnosing hemodynamically relevant RAS. The present study also demonstrated gadodiamide to be safe and well tolerated.
Kittner
Thomas
T
Hospital Dresden-Friedrichstadt, Germany. kittner-th@khdf.de
Rudolf
Jens
J
Fages
Joan Falco
JF
Legmann
Paul
P
Aschauer
Manuela
M
Repa
Imre
I
Alvares
Marta Rodriguez
MR
Savalegui
Ibone
I
Ittrich
Harald
H
Geterud
Kjell
K
de Kevviler
Eric
E
Ayuso
Juan
J
Lockhart
Mark E
ME
Blum
Alain
A
Iliasch
Herbert
H
Leisinger
Gerda
G
van Beek
E J R
EJ
Reid
Allan W
AW
Brown
Jeffrey J
JJ
Yu
Thomas C
TC
Flamm
Scott D
SD
Düber
Christoph
C
Judmaier
Werner
W
Reimer
Peter
P
Stiskal
Michael
M
Kramann
Bernhard
B
Wolff
Steve
S
Blankenstein
Christiane
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015901:Angiography, Digital Subtraction; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007275:Injections, Intravenous; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012078:Renal Artery Obstruction / Q000175:diagnosis*; D012449:Safety; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA