RATIONALE AND OBJECTIVES.
Two phase 3, mulliccnter studies were performed to compare the safety, tolerance, and efficacy of iopromide, an investigational nonionic contrast agent, with commercially available iohexol and ioversol, in patients requiring peripheral venography. In the randomized, double-blind, parallel studies, the three drug groups compared were iopromide 240 (Ultravist; Berlex Laboratories, Wayne, NJ), iohexol 240 (Omnipaque Injection; Sanofi- Winthrop Pharmaceuticals, New York, NY), and ioversol 240 (Optiray; Mallinkrodt Medical, Inc., St. Louis, MO).
The patient population consisted of 126 patients, 54 males and 72 females ranging in age from 20 to 88 years, who met predefined inclusion and exclusion criteria and had given informed consent. Each patient was studied with one drug only, and, generally, in one extremity only. Sixty-four patients received iopromide (mean dose, 155.8 mL), 41 patients received iohexo! (mean dose, 142.1 mL), and 21 patients received ioversol (mean dose, 182.0 mL).
Safety parameters, assessed at baseline and 24 hours postprocedure, included vital signs (blood pressure, pulse rate, and respiration rate), clinical laboratory parameters (hematology and blood chemistry), and physical examinations. Vital signs were also obtained during the procedure and 30 to 60 minutes postprocedure. When possible, serum creatinine was assessed at 72 hours postprocedure.
Adverse experiences (AEs) were monitored during the procedure and for 24 hours postprocedure. Heat/warmth and application- site pain that occurred during injections or within 5 minutes of the study procedure were considered indicators of tolerance and were rated by the patient on a scale of mild (1), moderate (2), or severe (3). Efficacy was assessed by the quality of the images, rated on a scale of excellent (3), good (2), poor (1), and no images (0), and by the ability to make a diagnosis.
No AEs were reported in either study group comparing iopromide (n = 23) to ioversol (n = 21). In the study comparing iopromide (n = 41) to iohexol (n = 41), AEs were reported by six (15%) iopromide patients and five (12%) iohexol patients. The most frequently reported AEs in the iopromide group were vasodilation in two (3%) and urticaria in two (3%) patients. No other AE was reported in more than one patient in the iopromide group. In the iohexol group, the only AE reported in more than one patient was pain, which was reported in two (3%) patients. Heat at the injection site was reported in eight (12.5%) patients in the iopromide group and four (6.5%) patients in the pooled comparator group. The respective mean scores were 0.13 and 0.O6. Pain at the injection site was reported in three (4.9%) iopromide patients and one (1.6%) patient in the pooled comparator group. The respective mean scores were 0.08 and 0.02. All tolerance parameter reports were rated mild except for one report of severe pain in an iopromide patient with bilateral upper extremity venous obstruction. None of these differences were statistically significant.
There were no clinically significant between-group differences in clinical laboratory parameters or physical examinations at the 24-hour evaluation when compared with baseline. Serum creatinine was measured at 72 hours in 17 iopromide patients, 9 iohexol patients, and no ioversol patients. No clinically relevant differences in mean changes from baseline were observed. The only statistically significant (P >.05) betweengroup difference occurring in vital sign parameters was a greater mean reduction in systolic blood pressure at the 30-to- 60-minute time point in the iopromide group (-6.09 mm Hg) than in the comparator group (—1.32 mm Hg). This difference did not indicate clinical significance.
Efficacy data evaluated by an independent, blinded reader was analyzed from 63 iopromide patients, 41 iohexol patients, and 21 ioversol patients. Visualization ratings were good or excellent in 63 (100%) iopromide patients, 39 (95%) iohexol patients, and 21 (100%) ioversol patients. The overall mean visualization ratings were 2.67, 2.54, and 2.62, respectively. One iopromide patient was excluded from efficacy analysis because of extravasation of contrast and inability to take any films. A final diagnosis was made in all patients included in the efficacy evaluation, except one iohexol patient who terminated the procedure before a sufficient quantity of contrast medium could be injected, and one ioversol patient who had nonfilling of the superficial vein of the thigh and narrowing of the left iliac vein, precluding sufficient opacification of the area of interest.
The results of these trials indicate that iopromide is well tolerated, and is safe and effective for use in peripheral venography.