Diabetes Mellitus, Renal Insufficiency
Conditions
Keywords
Iodixanol, Iopamidol, computed tomography, Patients with pre-existing renal impairment and diabetes
Brief summary
It is well known that X-ray contrast media can affect kidney function in some patients, especially when administered intra-arterially, and patients who already suffer from reduced kidney function and diabetes mellitus may be at increased risk. It is widely accepted to use low-osmolar or iso-osmolar contrast media, especially in patients at risk for contrast media-induced nephropathy. However, little is known about the intravenous use of X-ray contrast media in risk patients, such as contrast-enhanced CT examinations. The main purpose of this study is to evaluate and compare the effects on kidney function of two contrast media, the iso-osmolar iodixanol and the low-osmolar iopamidol in patients at risk of kidney damage associated with the injection of contrast media. Due to the iso-osmolar feature, it is expected less influence on renal function following administration of iodixanol. A standard hydration procedure, based on available guidelines will be given to all patients to prevent negative effects on the kidneys. Serum creatinine (SCr ) concentrations will be measured before and up to 7 days after contrast media administration to evaluate the effects on renal function.
Detailed description
GEHC has decided not to provide this detail
Interventions
DRUGIodixanol 320-Arm 1
DRUGIopamidol 300-Arm 2
Sponsors
ABX CRO
Examination Management Services Inc.
Covance
Quintiles, Inc.
Averion International Corporation
GE Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a combination of diabetes mellitus (type I or II) and renal impairment who are referred for a contrast-enhanced CT examination.
Exclusion criteria
* Concurrent administration of potentially nephroprotective or nephrotoxic drugs is not permitted. * Patients undergoing dialysis or kidney transplantation will not be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the Incidence Rate of Contrast Medium-Induced Nephropathy (CIN) Between Iodixanol and Iopamidol in Patients With Impaired Renal Function. | From baseline up to 3 days post contrast administration. | The primary endpoint was the incidence rate of CIN, defined as an intra-individual increase in serum creatinine (SCr) of greater than or equal to 44.2 µmol/L (greater than or equal to 0.5 mg/dL). Subjects with a pre-contrast (baseline) serum creatinine value greater than or equal to 1.5 mg/dL for males and greater than or equal to 1.3 mg/dL for females or eGFR of less than or equal to 50 mL/min/1.73m squared, and a post-contrast serum creatinine value available on days 2 or 3, administered greater than or equal to100 mL or greater than or equal to 1.5 mL/kg bodyweight IMP, without presence of any major protocol violations, and without evidence of other causes inducing acute renal dysfunction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Within 2, 3 and 7 days post contrast administration. | Overall Image Quality rated as Excellent, Good, Sufficient or Insufficient Poor by radiologists blinded to the contrast administration. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
656 subjects enrolled. 8 subjects did not continue on in the study. 7 of the 8 subjects discontinued the study prior to contrast media administration and 1 of the 8 subjects received a contrast media of unknown type and was excluded from the study. Subtracting 8 subjects from the total 656, a total of 648 subjects actually completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Iodixanol 320-Arm 1 Iodixanol 320 mg I/mL
Iodixanol 320-Arm 1 | 321 |
| Iopamidol 300-Arm 2 Iopamidol 300 mg I/mL
Iopamidol 300-Arm 2 | 327 |
| Total | 648 |
Baseline characteristics
| Characteristic | Iodixanol 320-Arm 1 | Iopamidol 300-Arm 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 188 Participants | 191 Participants | 379 Participants |
| Age, Categorical Between 18 and 65 years | 133 Participants | 136 Participants | 269 Participants |
| Age, Continuous | 66.4 years STANDARD_DEVIATION 12.02 | 66.5 years STANDARD_DEVIATION 12.01 | 66.4 years STANDARD_DEVIATION 12.01 |
| Region of Enrollment Austria | 11 participants | 12 participants | 23 participants |
| Region of Enrollment China | 45 participants | 48 participants | 93 participants |
| Region of Enrollment Czech Republic | 1 participants | 1 participants | 2 participants |
| Region of Enrollment France | 8 participants | 9 participants | 17 participants |
| Region of Enrollment Germany | 34 participants | 38 participants | 72 participants |
| Region of Enrollment Hungary | 6 participants | 8 participants | 14 participants |
| Region of Enrollment Italy | 4 participants | 5 participants | 9 participants |
| Region of Enrollment Poland | 60 participants | 55 participants | 115 participants |
| Region of Enrollment Russian Federation | 57 participants | 56 participants | 113 participants |
| Region of Enrollment Spain | 5 participants | 1 participants | 6 participants |
| Region of Enrollment Sweden | 6 participants | 8 participants | 14 participants |
| Region of Enrollment Switzerland | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United Kingdom | 10 participants | 14 participants | 24 participants |
| Region of Enrollment United States | 71 participants | 70 participants | 141 participants |
| Sex: Female, Male Female | 147 Participants | 170 Participants | 317 Participants |
| Sex: Female, Male Male | 174 Participants | 157 Participants | 331 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 321 | 0 / 327 |
| serious Total, serious adverse events | 6 / 321 | 6 / 327 |
Outcome results
Primary
Assessment of the Incidence Rate of Contrast Medium-Induced Nephropathy (CIN) Between Iodixanol and Iopamidol in Patients With Impaired Renal Function.
The primary endpoint was the incidence rate of CIN, defined as an intra-individual increase in serum creatinine (SCr) of greater than or equal to 44.2 µmol/L (greater than or equal to 0.5 mg/dL). Subjects with a pre-contrast (baseline) serum creatinine value greater than or equal to 1.5 mg/dL for males and greater than or equal to 1.3 mg/dL for females or eGFR of less than or equal to 50 mL/min/1.73m squared, and a post-contrast serum creatinine value available on days 2 or 3, administered greater than or equal to100 mL or greater than or equal to 1.5 mL/kg bodyweight IMP, without presence of any major protocol violations, and without evidence of other causes inducing acute renal dysfunction.
Time frame: From baseline up to 3 days post contrast administration.
Population: To calculate the incidence rate of CIN, divide the number of subjects affected by the total number of subjects dosed in each treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iodixanol 320-Arm 1 | Assessment of the Incidence Rate of Contrast Medium-Induced Nephropathy (CIN) Between Iodixanol and Iopamidol in Patients With Impaired Renal Function. | 9.90 percentage of subjects |
| Iopamidol 300-Arm 2 | Assessment of the Incidence Rate of Contrast Medium-Induced Nephropathy (CIN) Between Iodixanol and Iopamidol in Patients With Impaired Renal Function. | 10.63 percentage of subjects |
Secondary
Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination.
Overall Image Quality rated as Excellent, Good, Sufficient or Insufficient Poor by radiologists blinded to the contrast administration.
Time frame: Within 2, 3 and 7 days post contrast administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iodixanol 320-Arm 1 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Excellent | 220 Number of images |
| Iodixanol 320-Arm 1 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Good | 81 Number of images |
| Iodixanol 320-Arm 1 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Sufficient | 13 Number of images |
| Iodixanol 320-Arm 1 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Insufficient | 7 Number of images |
| Iopamidol 300-Arm 2 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Insufficient | 8 Number of images |
| Iopamidol 300-Arm 2 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Excellent | 207 Number of images |
| Iopamidol 300-Arm 2 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Sufficient | 9 Number of images |
| Iopamidol 300-Arm 2 | Assessment of Overall Image Quality Between Iodixanol and Iopamidol in Patients Undergoing Contrast-enhanced Multi-detector-row Helical Computed Tomography (MDCT) Examination. | Image Quality-Good | 103 Number of images |