Iodixanol and ioxaglate in cardioangiography: A double-blind randomized phase III study

doi:10.1016/S0009-9260(05)81016-5

Clinical Radiology

Volume 48, Issue 4, October 1993, Pages 268-272

https://doi.org/10.1016/S0009-9260(05)81016-5 Get rights and content

A new non-ionic, dimeric contrast medium iodixanol (Nycomed AS, Norway) has a very low osmolality and is isotonic with blood. It has been compared with ioxaglate (Hexabrix^®, Laboratoire Guerbet, France) in a double-blind, randomized, parallel trial. The aims of the trial were to evaluate and compare the safety (vital signs, adverse events, discomfort and clinicalchemical parameters in blood and urine) and radiographic efficacy (diagnostic information and radiographic density) of iodixanol 320 mg I/ml vs ioxaglate (Hexabrix^® 320 mg I/ml) in coronary angiography and left ventriculography. Seventy-six patients referred for cardioangiography, two patients were withdrawn, 36 receiving iodixanol and 38 ioxaglate were included in the trial. Six patients (16%) in the iodixanol group and 16 (42%) patients in the ioxaglate group reported adverse events (P=0.02). One serious adverse event occurred in the iodixanol group where a patient experienced transient cortical blindness and transitory global amnesia, but the patient recovered completely the day after the examination. Twenty-six patients reported injection-associated sensation of warmth in the iodixanol group versus 34 in the ioxaglate group (P=0.06). Following contrast injection there were no differences between the groups regarding vital signs (ECG, heart rate, left ventricular pressures). Both contrast media were well tolerated by the kidneys, and on average only minor effects on clinical-chemical parameters in blood and urine were observed in the two groups. The radiographic efficacy was good in both groups.

References (24)

PughND et al.
The effect of iodixanol, a new isotonic contrast agent on femoral blood flow in man
Clinical Radiology
(1992)
GertzEW et al.
Adverse reactions of low osmolality contrast media during cardiac angiography: a prospective randomized multicenter study
Journal of the American College of Cardiology
(1992)
GraingerRG
Annotation. Radiological contrast media
Clinical Radiology
(1987)
AlménT
Effects of iodixanol, iopentol, iohexol and metrizoate on femoral blood flow after injection into the femoral artery of the dog
Acta Radiologica (Diagnosis) Supplementum
(1987)
NossenJØ et al.
Experience with iodixanol, a new nonionic dimeric contrast medium. Preliminary results from the human phase I study
Investigative Radiology
(1990)
SkalpeIO et al.
The toxicity of non-ionic water-soluble contrast media in selective vertebral angiography. An experimental study in rabbits with special reference to the difference between monomeric and dimeric compounds
Neuroradiology
(1985)
SvalandMG et al.
Human pharmacokinetics of iodixanol
Investigative Radiology
(1992)
BolstadB et al.
Safety and tolerability of iodixanol. A dimeric, non-ionic contrast medium: an emphasis on European clinical phases I and II
Investigative Radiology
(1991)
GavantML et al.
Iodixanol in excretory urography: Initial clinical experience with a nonionic, dimeric (ratio 6:1) contrast medium
Radiology
(1992)
JakobsenJÅ et al.
Evaluation of renal function with delayed CT after injection of non-ionic monomeric and dimeric contrast media in healthy volunteers
Radiology
(1992)

BergKJ et al.

Iopentol in patients with chronic renal failure: its effects on renal function and its use as glomerular filtration rate parameter

Scandinavian Journal of Clinical Laboratory Investigation

(1992)

FeldmanRL

A comparison of heparinized low osmolality ionic and non-ionic contrast media in 500 patients undergoing cardiac angiography

Clinical Cardiology

(1990)

Cited by (54)

Metallic nanoparticles as X-Ray computed tomography (CT) contrast agents: A review
2020, Journal of Molecular Structure
Citation Excerpt :
Since late 70s, X-ray contrast agents were used to enhance to contrast of the investigated region [9]. Various clinical contrast agents are available in the market pros and cons of which were detailed and studied by many researcher [10–14]. Today, X-ray computed tomography contrast agent market was dominated by iodine based contrast agents (IBCA) where thousands tons of IBCA were used every year [15,16].
X-ray computed tomography vastly used in both medical purposes and in the research of biological and non-biological materials/samples. Some of the medical applications performed in the clinics requires special protocols where contrast agents may be needed to enhance the contrast. Iodine based contrast agents are commonly used in such applications. Iodine based contrast agents were found hazardous to the environment and some patients has iodine in tolerance due to thyroid origin diseases. Scientists from different fields try to develop contrast agents which can be an alternative to iodine based contrast agents. Metallic nanoparticles have potential to be used as CT contrast agent since metals has high X-ray attenuation and high density. Metal nanoparticles considered as toxic to the living organisms. Covering nanoparticles with organic molecule often reduce toxicity and enhance the biocompatibility. Decoration of nanoparticles with function groups give them targeting properties where special organ and/or tissue can be targeted. Up to now, different studies illustrated the importance of the multipurpose properties of the metallic nanoparticles. In this report, we assessed the metal nanoparticles reported as X-ray computed tomography contrast agent. For the first time in the literature we listed in vivo contrast enhancement, targeted drug delivery and dual/multipurpose imaging properties of each metallic nanoparticles. Therapeutic effects of metallic nanoparticles such as photothermal therapy and magnetic hyperthermia were also addressed. A chart showing relative contrast enhancement properties of the nanoparticles were produced.
Comparative effect of iso-osmolar versus low-osmolar contrast media on vascular attenuation, image quality, and heart rate changes in coronary CT angiography: A systematic review and meta-analysis
2020, Clinical Imaging
Citation Excerpt :
Our analysis demonstrated less heart rate change from baseline with a trend toward less heart rate variability in the IOCM group. Although several studies reported no difference in heart rate changes between the two contrast media groups [15–18,27], our findings were not surprising, as the use of iso-osmolar contrast media was associated with less heart rate changes in other published reports [31–34]. In coronary CT angiography, a low and stable heart rate is required to obtain high-quality images and to reduce the radiation burden [15].
Comparison of iso-osmolar contrast media (IOCM) and low-osmolar contrast media (LOCM) for vascular attenuation, image quality, heart rate changes, and common patient discomfort symptoms.
We searched PubMed, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL). We included only randomized controlled trials. Screening, data extraction, and quality assessment were done by three independent authors. RevMan 5.3 software was used for meta-analysis.
Nine studies (n = 1831 participants) were found eligible and included in the meta-analysis. There was no difference between the both contrast media for vascular attenuation (mean difference = −21.31; 95% confidence interval −49.81 to 7.19; p = 0.14), image quality (standardized mean difference = 0.13; 95% confidence interval −0.07 to 0.33; p = 0.19), heart rate variability (standardized mean difference = −0.61; 95% confidence interval −1.30 to 0.09; p = 0.09), heat sensation (risk ratio = 0.79; 95% confidence interval 0.56 to 1.11; p = 0.17), and nausea or vomiting (risk ratio = 0.82; 95% confidence interval 0.52 to 1.28; p = 0.38). Moreover, IOCM resulted in a heart rate that was lower by 0.9 beat per minute (bpm) compared to LOCM (mean difference = −0.92; 95% confidence interval −1.81 to −0.03; p = 0.04).
Both IOCM and LOCM have similar vascular enhancement, image quality, heart rate variability, and similar risk for patient discomfort. Furthermore, IOCM resulted in a slightly lower heart rate by 0.9 bpm.
Comparison of contrast enhancement, image quality and tolerability in Coronary CT angiography using 4 contrast agents: A prospective randomized trial
2015, International Journal of Cardiology
A meta-analysis of the risk of total cardiovascular events of isosmolar iodixanol compared with low-osmolar contrast media
2014, Journal of Cardiology
Citation Excerpt :
A total of 13 studies [1–3,7–9,12–18] that covered 6859 patients [3416 (49.8%) in the iodixanol group and 3443 (50.2%) in the LOCM group] eventually fulfilled our inclusion criteria and were used in this meta-analysis. A total of 13 investigations were reported in the 2 prospective cross-sectional studies [2,3] and 11 randomized controlled trials (RCTs) [1,7–9,12–18]. The study quality was generally excellent for the RCTs included, overall, two trials had a Jadad score of 5, five scored 4, two scored 3, and the remaining two scored 2.
The iso-osmolar contrast agent iodixanol may be associated with a lower incidence of cardiac events than low-osmolar contrast media (LOCM), but previous trials have yielded mixed results.
To compare the risk of total cardiovascular events of the iso-osmolar contrast medium, iodixanol, to LOCM.
Medical literature databases were searched to identify comparisons between iodixanol and LOCM with cardiovascular events as a primary endpoint. A random-effects model was used to obtain pooled odds ratio (OR) for within-hospital and 30-day events.
A total of 2 prospective cross-sectional studies and 11 randomized controlled trials (RCTs) (covering 6859 subjects) met our criteria. There was no significant difference in the incidence of within-hospital and 30-day cardiovascular events when iodixanol was compared with LOCM, with pooled OR of 0.72 (95%CI 0.49–1.06, p = 0.09) and 1.19 (95%CI 0.70–2.02, p = 0.53), respectively. Subgroup analysis showed no relative difference when iodixanol was compared with ioxaglate (OR = 0.92, 95%CI 0.50–1.70, p = 0.80) and iohexol (OR = 0.75, 95%CI 0.48–1.17, p = 0.21). However, a reduction in the within-hospital cardiovascular events was observed when iodixanol was compared with LOCM in the RCT subgroup (OR = 0.65, 95%CI 0.44–0.96, p = 0.03). Sensitivity analyses revealed that three studies had a strong impact on the association of within-hospital cardiovascular events between iodixanol and LOCM. Meta-regression analysis failed to account for heterogeneity. No publication bias was detected.
This meta-analysis demonstrates that there is no conclusive evidence that iodixanol is superior to LOCM overall with regard to fewer cardiovascular events.
Comparison of iodixanol 320 and iohexol 350 in image quality during 64-slice multidetector computed tomography: Prospective randomized study
2012, International Journal of Cardiology
The Relative Renal Safety of Iodixanol Compared With Low-Osmolar Contrast Media. A Meta-Analysis of Randomized Controlled Trials
2009, JACC: Cardiovascular Interventions
Citation Excerpt :
Of the 30 remaining studies, 14 were rejected because they were not randomized controlled trials. The remaining 16 studies satisfied the pre-determined inclusion criteria and were considered in the analysis (Fig. 1) (15,19–22,32–42). One study has not been published as a peer-reviewed report yet but was presented at the Transcatheter Therapeutics 2006 meeting (40).
We sought to compare the nephrotoxicity of the iso-osmolar contrast medium, iodixanol, to low-osmolar contrast media (LOCM).
Contrast-induced acute kidney injury (CI-AKI) is a common cause of in-hospital renal failure. A prior meta-analysis suggested that iodixanol (Visipaque, GE Healthcare, Princeton, New Jersey) was associated with less CI-AKI than LOCM, but this study was limited by ascertainment bias and did not include the most recent randomized controlled trials.
We searched Medline, Embase, ISI Web of Knowledge, Google Scholar, Current Contents, and International Pharmaceutical Abstracts databases, and the Cochrane Central Register of Controlled Trials from 1980 to November 30, 2008, for randomized controlled trials that compared the incidence of CI-AKI with either iodixanol or LOCM. Random-effects models were used to calculate summary risk ratios (RR) for CI-AKI, need for hemodialysis, and death.
A total of 16 trials including 2,763 subjects were pooled. There was no significant difference in the incidence of CI-AKI in the iodixanol group than in the LOCM group overall (summary RR: 0.79, 95% confidence interval [CI]: 0.56 to 1.12, p = 0.19). There was no significant difference in the rates of post-procedure hemodialysis or death. There was a reduction in CI-AKI when iodixanol was compared with ioxaglate (RR: 0.58, 95% CI: 0.37 to 0.92; p = 0.022) and iohexol (RR: 0.19, 95% CI: 0.07 to 0.56; p = 0.002), but no difference when compared with iopamidol (RR: 1.20, 95% CI: 0.66 to 2.18; p = 0.55), iopromide (RR: 0.93, 95% CI: 0.47 to 1.85; p = 0.84), or ioversol (RR: 0.92, 95% CI: 0.60 to 1.39; p = 0.68).
This meta-analysis including 2,763 subjects suggests that iodixanol, when compared with LOCM overall, is not associated with less CI-AKI. The relative renal safety of LOCM compared with iodixanol may vary based on the specific type of LOCM.

View all citing articles on Scopus

View full text

Iodixanol and ioxaglate in cardioangiography: A double-blind randomized phase III study

Clinical Radiology

Journal of the American College of Cardiology

Clinical Radiology

Effects of iodixanol, iopentol, iohexol and metrizoate on femoral blood flow after injection into the femoral artery of the dog

Acta Radiologica (Diagnosis) Supplementum

Experience with iodixanol, a new nonionic dimeric contrast medium. Preliminary results from the human phase I study

Investigative Radiology

The toxicity of non-ionic water-soluble contrast media in selective vertebral angiography. An experimental study in rabbits with special reference to the difference between monomeric and dimeric compounds

Neuroradiology

Human pharmacokinetics of iodixanol

Investigative Radiology

Safety and tolerability of iodixanol. A dimeric, non-ionic contrast medium: an emphasis on European clinical phases I and II

Investigative Radiology

Iodixanol in excretory urography: Initial clinical experience with a nonionic, dimeric (ratio 6:1) contrast medium

Radiology

Evaluation of renal function with delayed CT after injection of non-ionic monomeric and dimeric contrast media in healthy volunteers

Radiology

Iopentol in patients with chronic renal failure: its effects on renal function and its use as glomerular filtration rate parameter

Scandinavian Journal of Clinical Laboratory Investigation

A comparison of heparinized low osmolality ionic and non-ionic contrast media in 500 patients undergoing cardiac angiography

Clinical Cardiology