CONFIDEilTIALReference 3 N NYCOMEÐ
ItvlAclNG
22 December 1995
Trial No.D,YV039
CLINICAL TRIAL FINAL REPORT
TODLXANOL CWSTPAQUE.) IN PAEDIATRIC COMPUTEDTOMOcRAprry (CT) SCANtlrNc OF THE HEAD
A randomized, parallel, double-blind phase rrr çe¡¡p¿¡ison between iodixanol r2T0 mgVmland 320 mg Uml, and iohexol (Omnipaquej 300 mg UmI
at
Denartment o[raai3to11 nlnktinikerna,
Trial No.: DXV039U2 December 1995
N ffitR8,oSl of 5
SYNOPSIS
In úe present trial, iodixanol (VISIPAQUEo¡ was investi-eated in computed tomography (CT)
scuning of rhe head in paediatric patients. It was planned that iodixanol 320 mg Vmi would be
given to three patients in an open Phase II (pilot) part of the trial, whereas the main study would
be a Phase III randomized, parallel-group, double-blind comparison between iodixanol 27Q mg
Vml and 320 mg Vrnl, and iohexol (Omnipaquet) 300 mg Vml. However, it was decided that pilot
patients (Phase II) were not to be included and, therefore, only Phase Itr patiens were included in
this trial.
The trial was performed at Öst¡a Sjukhuset, Gothenburg, Sweden. The inclusion of patients
started in May 1994 and was completed in April 1995. During this time 75 patiens, randomized
into th¡ee groups, were included.
The objective of the srudy was to compare iodixanol and iohexol regarding safery and efflrcacy in
paediatric patients undergoing CT scanning of the head. Safery was assessed by means of
recording adverse events (including injection-associated discomfort and distress) and vital signs,
whereas efficacy wæ determined by evaluating the qualiry of overall diagnostic information
obtained from the contrast-enhanced scans of the head.
The main parameter for statistical analysis was the proportion of patients with any adverse
event(s), including injection-associated discomfort and distress, during and up to 24 hours after
the end of the examination.
It was outlined in the protocol that, when possible, blood and urine samples would be obtained
from in-patients when possible, for the purpose of monitoring elinical chemistry pa¡ameters.
However, none of the patients were in-patients, and as a consequence no blood and urine samples
were obtained.
Fì NYCOMEDItv'tAGNG
52 of5Trial No.: DXV039\22 December 1995
During this trial.25 patients received iodi.xanol 270 mgVmI,25 patients received iodixanol320
mg Vml, whereas 25 patients received iohe.rol300 mg Vrnl. The three groups were judged ro be
comPûrative regarding demographic cha¡acteristics, risk factors, relevant medical history,
presenting symptoms and medicarion (Table S.l).
A total of eleven patients experienced 13 advene events other than injection-associated
discomfort and dist¡ess (Table S.2). In the iodixanolZTQ mg Vml group six patients experienced a
total of seven adverse evenÈs other than injection-associated discomfort and dist¡ess (dry mouth,
two ceses of nausea, smell perversion, metallic taste in mouth, tiredness, urtica¡ia). All the evenß
were of mild intensity, and the fust five events listed were judged by the investigator to be
conEast medium-relæed, the two last-mentioned events were classified as uncertain.
In the iodixanol 320 mg Vml group, two patients experienced adverse events other than
discomfort and distress (tiredness and eryttrema) (Table S.2). Both events were of mild intensity.
The cause of the tiredness was classified as not related to contrast medium, whereas the cause of
the other event (erythema) was classified as uncertain.
Three patients in the iohexol 300 mg Vml group reported four adverse events other than injection
associated discomfort and distress. The intensity of two of these events was mild (nause4 taste
perversion), whereas the other rwo events we¡e of moderate intensity (nausea, vomiting). The
cause of taste perversion was judged to be the contrast medium, whereas the causes of the other
three events were classified as uncertain.
A total of nine patients reported injection-associated discomfort; four patients in the iodixanol
270 mg Vml group, three patients in the iodixanol 320 mgVmi group and two in the iohexol
group (fable S.2). In the iodixanol2T0 mg Vml group the kind of discomfort reported was pain
for one patient, whereas three patients reported a sensation of heat. These events were all of mild
intensity. In the iodixanol 320 mg Vml group, one patient had a feeling of heat whereas two
Sl l;mng'"Trial No,: DXV039\22 December 1995 53 of5
patients had a feeling of cold. All events were of mild intensity. Two patienß in the iohexol
group had a mild sensation of heat.
Injection-associated distress ("sweat pearls on the chin") was reported to have occurred in one
patient only. The occulrence wæ of mild intensity a¡d the patient was given iodixanol 21Q mg
Vmt (Table S.2).
ln order to compare the proportions of patients with any adverse event(s), including injection-
associated discomfo¡t and distress, berween each of the two iodixanol goups versus the iohexol
group, Fisher's E.ract test w¿¡s used rwice. The results showed that the distributions were not
significantly different (iodixalol 270 mg Vmi versus iohexol, p=0.35; iodixanol320 mg Vnrt
versus iohexol, p= 1.00).
No serious adverse event occurred during the conduct of this trial.
The number of patients in whom the overall diagnostic information acquired f¡om the contrast-
enhanced CT scans was scored as excellent, good, poor and inadequate are shown in Table S.3.
The quality of overall diagnostic inforsration in the iodixa¡rol27O mg Vnrl group was classified as
excellent for 17 patients and good for eight patients. In the iodixanol 320 mg VmI grcup, 2l cases
were rated as excellent and four æ good. In the iohexol 300 mg Vml group overall diagnostic
information was rated æ excellent for 18 patients, good for six patients and inadequate for one
patient.
Separate V/ilcoxon two-sample tests were used to comp¿¡¡e overall diagnostic information
between the two iodixa¡rol groups versus the iohexol $oup. A p-value of 0.85 was obtained
when comparing the 270 mg Vml group and the iohexol300 mg Vml group. The comparison
between the iodi.xanol320 mg Vml group and the iohexol300 mg Vml group gave a p-value of
0.29. Therefore, no statistically significant difference was found between either of the iodixa¡rol
S\ usns,"Trial No.: DXV039U2 December 1995 54of5
groups versus the iohexol group with regard to effÌcacy when the significance level was set to
SVo.
Summing up, no statisdcally sigrificant differences were found between the iodixanol groups and
the iohexol group, as regards the proportion of patients with adverse events and in terms of
overall diagnostic information (effrcacy).
In conclusion, iodixanol in the two concentrations tested, 27Q arnd 32O mg Vml, was effective and
well tolerated when administrated intravenously for CT scanning of rhe head in paediatric
patients.
Tn¿l No.; DXV039\22 December 1995
N HERg'o55 of5
Table S. I
D E}f O GR,\ PHI CSÆ(\O WN RISK
FACTORS
Iodíxanol
270me.Ar¡¡'l
Iodixanol
320 mgVml
Iohe.rol
300 me Vml
Numhe¡ of ors. ¡antlomized 1S 25 1{
Yumher of ors e.rarnined wi¡i contr¿st ffemaley'malc) 25 fl1/l r ) 25 fi0/15) 25 ( t3^2\
Mc¡n ase (srd) monrhs l0 r. r (ó2.2) 105 2 (50.0) 97 (62;t\
.llern heishr (s¡d) cm 125.6 (32.9\ 132.0 (28.-r) l2ó.2 r3 I -3)
Mean weisht (srd) ks 3t.5 r17.5) 3l I ( 15.8) 28.8 flJ 8t
E¡ìnic oriein: Crucasian fothcr) 23 (2\ 24 lt) 23 (2\
Number of oo with risk factors lNo. of risk facron) 515) 3(.r) 5r5)
DOSAGE
Mean volume iniected mean lstd) nl 89.1 (4s.r) 89.7 @07\ 84.8 141.5)
Mean dosase iodine mcrn (s¡d) s I 24.t iL2.2\ 28.7 ( r 3.0) 25.4 r12.5
Me¡n dosase iodine mern fstd) s lite b.w 0.78 (0.07) 0.94 (0.06) 0.89 (0.03)
Table S.2
Iodlranol
?llÙmùïlml
',-Iodix¡nol
320'msVmI
Iohexol
30O mqVmI
ADVERSE EVENTS other than discomfort/disr¡ess,
No. ofots. (9c)
6 (24) 2 (8) 3 02)
DISCOMFORT. No. of ps. (%) 4 û6) 3 u2\ 2 r8)
DISTRESS. No. of oa. (7o) I t4) 0 0
Table S, 3 EFFICACY RESULTS; OYERALL DIAGNOSTIC INTORIVÍATION
GROTJP Excellent Good : Poor fnadequåt€
lodixanol 270ms.Uml t7 I 0 0
lodiranol 320 ms I/mI 2l 4 0 0
Iohexol 300 ms Uml l8 6 0 I
Total 56 l8 0 I
