Comparison in myelography between iodixanol 270 and 320 mgI/ml and iotrolan 300 mgI/ml: a multicentre, randomised, parallel-group, double-blind, phase III trial

The objective of the trial was to compare the safety and efficacy of the non-ionic, dimeric, isotonic contrast medium iodixanol (Visipaque 270 and 320 mgI/ml) with those of iotrolan (Isovist 300 mgI/ml) in myelography. After lumbar or cervical puncture, 315 patients were examined in a multicentre, double-blind, randomised, comparative myelography study. Image quality, changes in vital signs, immediate and delayed adverse events were registered. There was a tendency for better images with iodixanol 320 than with iodixanol 270 and iotrolan 300, but the overall quality was good or excellent with all products. The frequency of patients reporting adverse events and headache varied much across centres, but there was no statistically significant difference between the contrast media. The incidence of events was higher after lumbar puncture than after cervical puncture, in women rather than in men, and after puncture with a 22-gauge (G) bevel-tipped needle compared with a 24 G Sprotte needle. The frequency of headache did not correlate with the absence of pathology. The higher iodine concentration in iodixanol 320 could be an advantage for film quality. When compared with iotrolan 300, iodixanol 320 and 270 give similar incidences of adverse events, including headache.     

Iodixanol in intra-arterial cerebral digital subtraction angiography: a comparison with iohexol

We randomised 86 patients undergoing intra-arterial cerebral digital subtraction angiography (IADSA) to receive iodixanol (Visipaque; Nycomed, Oslo, Norway) 150 mgI/ml or iohexol (Omnipaque; Nycomed) 140 mgI/ml. The efficacy and safety of these two contrast media were compared: efficacy by evaluating the diagnostic information and radiographic density yielded by the angiograms, safety by recording all discomfort connected with the injections, and all adverse events up to 24 h after the investigation. Diagnostic information was optimal in all patients and the overall radiographic density optimal in all but one (iohexol) (P=0.49). A feeling of warmth, the only discomfort reported, was experienced by 43% and 54% of patients receiving iodixanol and iohexol, respectively (P=0.26). Two patients in the iodixanol group and five in the iohexol group reported one adverse event (nausea, dizziness, visual disturbance or paraesthesiae) (P=0.30); all were of mild severity except for one moderate adverse event in each group. Iodixanol 150 mgI/ml and iohexol 140 mgI/ml were demonstrated to be suitable for IADSA, with no clinically or statistically significant differences in efficacy, discomfort or adverse events.     

Iodixanol in paediatric gastrointestinal imaging: safety and efficacy comparison with iohexol

Iodixanol (Visipaque) is a dimeric, non-ionic iodinated contrast medium that is isotonic with blood at all clinically relevant concentrations. Iodixanol was compared in a randomized, double blind, parallel group, phase III multicentre trial with a monomeric, non-ionic contrast medium, iohexol (Omnipaque), at two concentrations assessing safety, tolerability and radiographic efficacy during contrast enhanced gastrointestinal radiography examinations of children. 154 children entered the trial; 152 formed the safety population and 147 the efficacy population. All examinations were performed following standard departmental practice. Children were assigned into either a high or low concentration group (iodixanol, 150 mgI ml(-1) and 320 mgI ml(-1) vs iohexol, 140 mgI ml(-1) and 300 mgI ml(-1)). The primary outcome measure for efficacy was the overall quality of visualization, which was assessed using a 100 mm visual analogue scale (VAS). The secondary efficacy variables assessed were quality of contrast opacification, mucosal coating and overall quality of diagnostic information. Safety evaluation involved patient follow-up for at least 48 h. Taste acceptance was also assessed. There was no statistically significant difference between the two contrast media with regard to the primary and secondary efficacy variables assessed, although higher ratings were observed for iodixanol. The 100 mm VAS score overall was 86 mm for iodixanol and 82 mm for iohexol (95% confidence interval -2.56, 10.42). The frequency of adverse events was lower for patients receiving iodixanol. Adverse events, mainly diarrhoea, occurred in 12 patients (16.2%) in the iodixanol group and 28 patients (35.9%) in the iohexol group. This reached statistical significance (p=0.006). Overall, iodixanol is well suited for examinations of the gastrointestinal tract, giving good efficacy results and fewer adverse events than iohexol.     

A double-blind, prospective, randomized, multicenter group comparison study of iopromide 240 vs iohexol 240 in myelography

The aim of this study was to evaluate the safety and efficacy of iopromide 240 mgI/ml in comparison with iohexol 240 mgI/ml in myelography. A total of 421 patients in seven centers and four countries received an average of 11.9 ml of either iopromide 240 (278 patients) or iohexol 240 (143 patients) for X-ray and/or CT myelography in a randomized (2:1), prospective, double-blind study. All patients were followed up 3–4 h after the procedure, and 327 patients remained hospitalized for 24 h. In 82 patients an EEG was recorded prior to as well as 3–4 h and 24 h after myelography. Physical examinations, including measurement of vital signs, were performed in all patients at these time points. The results were subject to statistical analysis with the primary variable being the incidence of adverse events. Both contrast media (CM) were equally effective in terms of opacification. The rating for opacity was “good” or “excellent” in 88 % for both CM. Four patients (iopromide group: n = 3; iohexol group: n = 1) had transient EEG changes but did not show clinical symptomatology. The overall rate of patients experiencing any adverse event (AE) was 16.9 % for iopromide 240 and 14.0 % for iohexol 240. Equivalence testing was inconclusive; however, the results indicated equivalence. The rate for AEs considered as study-drug related was slightly lower with iopromide 240 than with iohexol 240 (7.2 vs 7.7 %, respectively). Neither unknown nor unexpected AEs known for myelographic X-ray CM nor serious adverse events were observed. Iopromide 240 and iohexol 240 are equally safe and effective and can be recommended for myelography. Received: 19 August 1998; Revision received: 26 November 1998; Accepted: 4 February 1999     

Iodixanol vs iopamidol in intravenous DSA of the abdominal aorta and lower extremity arteries: a comparative phase-III trial

Iodixanol (visipaque, 320 mgI/ml) was compared with iopamidol (Solutrast, 370 mfI/ml) in a double-blind, randomized, parallel group, intravenous DSA phase-III trial for evaluation of safety and efficacy. A total of 117 patients received iodixanol (n = 60) or iopamidol (n = 57). Diagnostic efficacy was evaluated using categoric and visual analogue scales. Discomfort and adverse evenets were recorded. A total of 39 patients collected urine up to 72 h after the examination for analysis. Diagnostic efficacy and radiographic density were similar in both groups. Discomfort was milder with iodixanol. The difference between the frequency of adverse events between both groups (iodixanol = 7, iopamidol = 2) was without statistical significance. Creatinine clearance was slightly more affected by iodixanol, whereas the increase in renal excretion ofN-acetyl-beta-glucosaminidase (NAG) in the first 24 h collection period after the examination was significantly higher (p < 0.01) with iopamidol. Iodixanol was of equal diagnostic efficacy compared with iopamidol despite its reduced iodine content. Both contrast media are well suited for IV DSA.     

Iodixanol in cerebral computed tomography: a randomized, double-blind, phase-III, parallel study with iodixanol and iohexol

Iodixanol is a new nonionic dimer, isotonic with blood at all clinically relevant concentrations. Iodixanol (270 mg I/ml) was compared in a double-blind, randomized, parallel-group, phase-III study to the monomeric nonionic iohexol (300 mg I/ml) for evaluation of safety, tolerability and radiographic efficacy during cerebral CT. One hundred adult patients scheduled to undergo contrast-enhanced cerebral CT were randomly allocated to receive either iodixanol or iohexol. All completed the trial. Safety was evaluated by recording discomfort and other adverse events, tolerance by assessing intensity and incidence of discomfort. Radiographic efficacy was assessed from the diagnostic information and the radiographic density. No serious adverse events occurred. One patient (2 %) in the iodixanol group and one patient (2 %) in the iohexol group experienced a transient reddening at the neck and lower neck-line, respectively. Both contrast agents were well tolerated. One patient (2 %) in the iodixanol group and two patients (4 %) in the iohexol group experienced a sensation of warmth (discomfort) in connection with the injection. No difference between the two contrast media were noted radiographically. This comparison between iodixanol and iohexol showed both contrast media to be safe, well-tolerated and efficacious for use in cerebral CT. Received: 8 June 1998; Revision received: 26 August 1998; Accepted: 7 October 1998     

Iohexol compared to metrizamide in cervical and thoracic myelography

Summary A randomized double blind study with iohexol (Omnipaque) and metrizamide (Amipaque) in cervical myelography was performed in 50 patients, 29 with iohexol and 21 with metrizamide. The myelographies were performed either with lumbar or with C₁–C₂ puncture in about equal groups, using 300 mg I/ml and 240 mg I/ml of the contrast media respectively. The image quality was equal with both contrast media, excellent in about 4/5 and good in 1/5 of the examinations. Subjective side effects were twice as frequent with metrizamide as with iohexol. The most frequent side effect was headache, occurring in 34% with iohexol and in 67% with metrizamide. Altogether 24% or the patients had EEG changes after iohexol as compared to 47% after metrizamide. All EEG changes were slight dysrythmia-except in three patients with spike activity after metrizamide. These were the only ones with mental reactions as well. It can be concluded that in this trial iohexol was better suited for cervical myelography than metrizamide.     

Lumbar myelography with iohexol and metrizamide: a comparative multicenter prospective study

Diagnostic quality of radiographs and adverse reactions associated with the use of metrizamide and iohexol as contrast agents in lumbar myelography were compared in a prospective randomized double blind study in 350 patients at seven centers. The contrast media were administered in comparable volumes at a concentration of 180 mg I per ml. Overall quality of radiographic visualization was graded good or excellent in 95% of 175 metrizamide studies and in 98% of 175 iohexol studies. Ninety-three patients examined using metrizamide (53%) and 130 patients examined using iohexol (74%) experienced no discomfort during or after myelography. Postmyelographic headache was associated with 38% of metrizamide examinations and 21% of iohexol examinations. Nausea and vomiting were also more common with metrizamide. Five patients examined using metrizamide (3%) experienced transient confusion and disorientation following lumbar myelography. No such reactions were observed following iohexol myelography.     

Iodixanol and iohexol in cardioangiography. A comparative vectorcardiographic study

Purpose: The non-ionic dimeric contrast medium (CM) iodixanol is isotonic with blood through the addition of electrolytes. In this study, we evaluated computerised dynamic vectorcardiography (VCG) as a tool in CM research by comparing the electrophysiological effects of iodixanol with those of the low-osmolar CM iohexol.Material and Methods: A total of 119 patients referred for cardioangiography were included in this double-blind, randomised, parallel comparison of iodixanol (320 mg I/ml) and iohexol (350 mg I/ml). VCG was recorded and different VCG parameters were analysed. General tolerability, safety and radiographic efficacy were also assessed.Results: Iodixanol induced less changes than iohexol in all VCG parameters and the sensation of warmth was significantly milder after iodixanol, but both CM were well tolerated. VCG might be useful in future studies to analyse electrophysiological effects caused by CM.     

Iohexol vs. ioxaglate in lower extremity angiography: a comparitive randomized double-blind study in 80 patients

The aim of this study was to detect clinically relevant differences between iohexol 300 mgI/ml and ioxaglate 320 mgI/ml in lower extremity arteriography. In this randomized double-blind study, 40 patients were examined with iohexol and 40 patients with ioxaglate. Adverse events were evaluated by recording the time of onset and the duration of possible adverse events: during or immediately following the contrast medium injections, after 6 h, and after 24 h following these injections. Heat and pain were scored on visual analog scales. The amount of contrast medium and possible thromboembolic complications were noted. Image quality was evaluated. There were no significant differences in the total amounts of contrast agent adminstered (ioxaglate mean 121.5 ml vs. iohexol 125.1 ml), scores for heat (ioxaglate mean 6.1 vs. iohexol 6.1) and pain (both agents mean 2.35). Nausea/vomiting was noticed significantly more frequently with ioxaglate (ioxaglate seven patients vs. iohexol one patient (χ², P < 0.05)). Thromboembolic complications were not detected. Opacification of vessels was optimal in all patients. No clues were found indicating that one of the agents was better tolerated 6–24 h after the procedure than the other. Nausea/vomiting occurred significantly more frequent with ioxaglate; no further clinically relevant differences were detected.     

Comparison of iohexol 300 mg I/ml and Hexabrix 320 mg I/ml in central angiography

Summary Iohexol 300 mg I/ml and Hexabrix 320 mg I/ml have been compared in a randomized, double blind, parallel study, to evaluate hemodynamic parameters, diagnostic information and adverse reactions. A total of 55 patients entered the study, one of them was later excluded, bacause both contrast media were given by mistake. In the included material, 21 patients were given iohexol 300 mg I/ml in 55 selective injections and 23 patients Hexabrix 320 mg I/ml in 65 selective injections. The median total dose was 52 (12–88) ml in the iohexol group and 51 (13–118) ml in the Hexabrix group. No changes in heart rate were seen. Angiograms of good or excellent quality were obtained, and no difference between the two media was shown. No serious adverse reaction accured, and no statistical significant difference was found between the two media with respect to subjective patient reactions. The results indicate that the non-ionic, low-osmotic contrast medium iohexol is well tolerated in cerebral angiography with respect to the parameters tested. No statistical significant difference was found in any of these parameters between iohexol and Hexabrix.     

Adult myelography with iohexol

An open, multicenter trial of adult myelography was carried out at six centers in 117 patients with iohexol (Omnipaque) 240 mg I/ml and 300 mg I/ml to determine whether there was a difference in visualization or side-effects when a lumbar or cervical approach was used to visualize the areas where disease was suspected. One hundred and thirteen myelograms were analysable. In over 85% of the myelograms with a lumbar approach, visualization of the area injected was excellent or good. Just over half of these were obtained with the intention of visualizing primarily the cervical area, and in 93% of these visualization was good or excellent at that site. In 100% of the cervically injected myelograms, visualization was excellent in the cervical area. Areas more distant from the injections were well visualized in the majority of patients. There was no significant difference overall in visualization with either of the two concentrations of iohexol used. There were 59 side-effects, mostly mild in nature; 40 of them occurred in 50 patients receiving the higher concentration and 19 in 63 patients receiving the lower concentration. The most common side-effect was headache (23 patients). Nystagmus was the only severe side-effect and occurred in only one patient having cervical myelography. The patient made a complete recovery within 36 hours.     

Injection-associated pain in femoral arteriography: A European multicenter study comparing safety, tolerability, and efficacy of iodixanol and iopromide

Purpose To evaluate injection-associated pain, safety, and efficacy with the isotonic contrast medium iodixanol (Visipaque 270 mg I/ml) compared with iopromide (Ultravist 300 mg I/ml) in femoral arteriography. Methods A multicenter, double-blind, randomized, parallel-group clinical investigation was carried out in 54 hospitals in Europe. Of the patients evaluated, 1225 received iodixanol and 1227 iopromide in conventional and/or digital subtraction angiography. Results The iodixanol group reported statistically significantly less injection-associated pain (0.9%) than the iopromide group (9.5%) (p<0.001). Further, 4.1% in the iodixanol group experienced pain and/or severe heat sensation vs 19.8% in the iopromide group (p<0.001). In the iodixanol group, 1.8% of the patients experienced contrast-related adverse events vs 2.4% in the iopromide group (p=NS). Overall diagnostic information was optimal for 94.1% in the iodixanol group and 95.3% in the iopromide group (p=NS). Conclusions Iodixanol 270 mg I/ml causes significantly less injection-associated pain during femoral arteriography and is as safe and efficatious as iopromide 300 mg I/ml.     

Iohexol in paediatric myelography

Summary Iohexol was introduced by lumbar puncture in a series of 148 consecutive children aged between 5 days and 16 years referred for myelography; no patient was excluded. Initially, iohexol 180 mgI/ml was used in dosage proportional to body weight varying between 5 ml and 15 ml. During the later part of the trial concentration of iodine was increased to 240 mg/ml for cases in which the dorsal region was of particular interest (69 patients) and to 300 mg/ml for 8 cervical studies. The total dose ranged up to 4.8 g and varied between 0.03 g and 0.51 gI/kg body weight. In all patients, neurological examinations were performed before and at 24 h and observations for adverse reactions continued over a period of 48 h. The contrast medium was run up to the foramen magnum or basal cisterns in 128 patients and to the upper dorsal region in the other 20. In the first 62 patients vital studies were performed over the period of the myelogram and for 24 h following, and an additional limited neurological examination was made at 6 h, and in the first 26 cases of the series EEG's were done before and at 24 h after the myelogram. Minor variations in pulse rate and blood pressure were observed but these were not of sufficient magnitude to be of clinical significance. In 7 patients there was minor, generally slow wave abnormality on the EEG taken after the procedure, but no spike or epileptogenic activity was obserse reactions. Focal increase in neurological signs, associated with backache and probably related to the mechaniccs of lumbar puncture and myelography, occurred in 3 tumour patients; otherwise no change in neurological condition was observed in any case. Minor reactions were observed in 24 other patients (16.2%); vomiting 14 (9.5%), headache 8 (5.7%), backache 6 (4.1%), stomache ache 2 (1.5%), mild pyrexia 3 (2.0%). The incidence and severity of these reactions was considerably less than with metrizamide myelography and all resolved within 2 days of the iohexol injection. In conclusion, iohexol has significant advantages over previously used non-ionic contrast media and is suitable for paediatric myelography.     

Myelography with iohexol (Omnipaque): review of 300 cases

The side effects of iohexol were evaluated in the 300 patients who had nonemergency myelography over a 9 month period. No patients studied with myelography were excluded from the iohexol trial. Age range was 14-86 years. Introduction was by lumbar puncture in 206 patients and by lateral C1-C2 injection in 94. Side effects, including discomfort, were denied by 81.3% of the patients. The other 18.7% had adverse reactions, the most common being headache, reported by 11% of the total population studied. Image quality was judged unsatisfactory in 8.1% of cervical myelograms and in 2.6% of lumbar myelograms. With lumbar injection, cervical myelograms were judged to be inadequate in 13.5%; with cervical injection, lumbar myelograms were inadequate in 25%. Iohexol caused significantly fewer side effects in the 300 patients than would have been expected with metrizamide. The low cost and ease of use are additional factors that favor iohexol as the contrast agent of choice for myelography.     

Iohexol versus iopamidol for cervical myelography: a randomised double blind study

A randomised double blind trial of iohexol and iopamidol in cervical myelography by both lumbar puncture and direct puncture techniques is reported in one hundred consecutive patients. All patients had EEG examination before and 6-8 h after the myelogram and for each a questionnaire regarding adverse reactions was completed at set intervals. The side effects, radiographic quality of the examination and production of sharp wave activity on EEG were equivalent in the iohexol and iopamidol series. Contrary to previous reports, we consider that iohexol and iopamidol are equally acceptable for all forms of myelography.     

Comparison of double-contrast CT arthrography image quality with nonionic contrast agents: isotonic dimeric iodixanol 270 mg I/mL and monomeric iohexol 300 mg I/mL

RATIONALE AND OBJECTIVES: The authors evaluated the image quality on delayed CT arthrography images with the use of the nonionic dimeric contrast agent, iodixanol 270 mg I/mL, compared with iohexol 300 mg I/mL. METHODS: A total of 132 patients with shoulder pain were included in a randomized, parallel, double-blind study. Sixty seven patients received iodixanol and 65 patients received iohexol. Patients underwent two CT-arthrography examinations: the first was performed 20 to 30 minutes after contrast injection and the second, 50 to 70 minutes after contrast injection. Data from 31 patients were excluded from the efficacy analysis. The overall quality of CT arthrography images was graded into four categories: excellent, good, moderate, and bad. RESULTS: The overall quality of delayed CT arthrography images was significantly better in the iodixanol group (P = 0.001, alpha = 0.05). On the first CT examination, image quality was good or excellent in 88% of the cases in the iodixanol group and in 96.1% in the iohexol group. The results on the delayed CT arthrography examination indicated that image quality was good or excellent in 88% of the cases when iodixanol was used and in 63.5% when iohexol was used. CONCLUSIONS: The overall quality of delayed images was significantly better with iodixanol than with iohexol.     

Intra-arterial digital subtraction angiography with isotonic dimeric (iodixanol) and monomeric (iohexol) nonionic contrast media: radiographic,clinical and neurophysiological evaluation

Monomeric (iohexol 300 mg I/ml) and dimeric (iodixanol 270 mg I/ml) nonionic contrast media were compared in a double-blind, randomised, parallel group trial. Safety and efficacy of the media in intra-arterial cerebral digital subtraction angiography were evaluated by assessing adverse events, discomfort, EEG, heart rate and quality of radiodiagnostic information. Seventy-six patients underwent selective injection of the carotid and/or vertebral arteries. Both contrast media were well tolerated. No serious adverse events occurred. No effects on heart rate and EEG were evident. The arteriograms were of high quality and overall diagnostic information was optimal in 94% of the examinations. No clinically important differences between the two contrast media were found.     

High-dose iohexol myelography

Lumbar myelography was performed with high volumes of iohexol (15-24 ml) at a concentration of 180 mgI/ml (average dose, 20 ml) in 48 patients. In 44 patients receiving more than the currently recommended upper dose limit of 17 ml, the frequency of headache (41%), nausea (14%), and vomiting (9%) was comparable to results for routine-dose lumbar metrizamide myelography. Overall, adverse reactions were more frequent, particularly at the highest dose levels, than reported for conventional-dose iohexol myelography. However, there were no occurrences of neuropsychiatric disorder, encephalopathy, or seizure. High-dose technique allows superior visualization of upper lumbar and conus detail and may be advantageous in patients with large subarachnoid spaces and in multi-level examinations. This study supports the results of previous trials that suggested the relative safety of iohexol as a contrast agent and extends those observations to a higher dose range. Because of the increased rate of adverse reactions at the highest dose levels (despite the absence of major adverse reactions), iohexol should continue to be used conservatively, with doses carefully tailored to each examination.     

Outpatient lumbar radiculography: comparison of iopamidol and iohexol and a literature review

A prospective study of 261 patients undergoing lumbar radiculography using 12 ml iopamidol (200 mgI/ml) was undertaken to determine whether the procedure could be performed safely on an outpatient basis. No statistically significant differences in the incidence and severity of side-effects were found between the 132 outpatients and 129 inpatient controls. Nine outpatients had to be kept in hospital at the end of a 4-h observation period and a further two outpatients were re-admitted to hospital because of severe side-effects. The current study was compared with a preceding study of identical design, already published, in which 200 patients underwent lumbar radiculography with 10 ml iohexol (240 mgI/ml). No statistically significant differences in the incidence and severity of side-effects between the two contrast media were evident up to 24 h after the examination. In the period between 24 h and 7 days, the incidence and severity of headache, nausea and dizziness were all significantly greater in the iopamidol group. Although outpatient radiculography can be performed safely with both contrast media, the higher incidence of delayed side-effects in the iopamidol patients prompts the authors to express a preference for iohexol for intrathecal use. The increased incidence of adverse reactions in female patients and the literature comparing iopamidol and iohexol for myelography are discussed.