Chronic Renal Impairment, Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to compare the incidence of contrast-induced nephropathy (CIN) following the administration of iopamidol-370 (Iopamiro-370) and iodixanol-320 (Visipaque 320) in patients with moderate-to-severe chronic kidney disease and diabetes mellitus undergoing cardiac angiography.
Detailed description
This was a Phase IV, multicenter, randomized, double-blind, parallel-group comparison of iopamidol-370 and iodixanol-320 in patients at high risk for CIN, i.e., patients with: * Stage 3 or 4 CKD (SCr level of ≥ 1.5 mg/dL for men and ≥1.3 mg/dL for women or eGFR between 15 and 50 mL/min, and * Diabetes mellitus who would undergo clinically indicated cardiac angiography procedures. Approximately 10 investigative centers were to participate in this study. This study was to enroll approximately 220 patients to ensure that 200 evaluable patients were able to complete the study according to this protocol. Patients were to be randomized to receive either iopamidol-370 or iodixanol-320. Each patient was to be evaluated for the occurrence of CIN within 48 to 72 hours postdose.
Interventions
Iopamiro-370 (Iopamidol injection 76%) is provided in single dose bottles/vials, ready to use, aqueous, nonpyrogenic, colorless to pale yellow sterile solution
DRUGiodixanol
Visipaque 320 (iodixanol) injection is provided in bottles/flexible containers, ready to use sterile, pyrogen-free colorless to pale yellow solution
Sponsors
Bracco Diagnostics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provides written Informed Consent and is willing to comply with protocol requirements * Is \>18 years of age * Has a documented predose serum creatinine level of ≥1.5 mg/dL for men and ≥1.3 mg/dL for women or predose eGFR of \>15 and ≤50 mL/min/1.73 m2, calculated via the Modification of Diet in Renal Disease (MDRD) formula from a SCr obtained within 72 hours of enrollment into the study; * Diagnosed as having diabetes mellitus (Type 1 or Type 2) treated with insulin or oral hypoglycemic agents for at least 6 months * Is referred for cardiac angiography with or without percutaneous coronary intervention; * If at the discretion of the Investigator is receiving or will be receiving a prophylactic medication for renal function, the medication is one that is permitted by this protocol (N acetylcysteine, 1200 mg twice daily on the day before and on the day of the cardiac angiography procedure); * Undergoes or is scheduled to undergo pre, peri, or post procedure hydration permitted by this protocol, i.e.: 154 mEq/L sodium bicarbonate solution, administered intravenously at 3 mL/kg/hr for 1 hour before cardiac angiography, followed by an infusion of 1 mL/kg/hr during and out to 6 hours after cardiac angiography, or 154 mEq/L sodium chloride solution (0.9% normal saline), administered intravenously at 1 mL/kg/hr for 8 12 hours before cardiac angiography, followed by an infusion of 1 mL/kg/hr during and out to 8-12 hours after cardiac angiography
Exclusion criteria
-Is a pregnant or lactating female. Exclude the possibility of pregnancy: by laboratory testing on-site at the institution (measurement of serum or urine beta human chorionic gonadotropin) within 24 hours prior to the start of investigational product administration by history (e.g., tubal ligation or hysterectomy, post menopausal with a minimum 1 year without menses) * Has a history of hypersensitivity to iodine-containing compounds; * Has unstable renal function (i.e., acute worsening of renal function, as determined by the Investigator, that has been observed in the 7 days prior to enrollment) and/or is in acute renal failure; * Has stage 5 chronic kidney disease or end-stage renal disease (i.e., estimated glomerular filtration rate \[eGFR\] \<15 mL/min/1.73 m2) * Has severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association (NYHA); * Has uncontrolled diabetes, as determined by the Investigator; * Has received an iodinated contrast agent within 7 days prior to the administration of the study agent or is scheduled to receive an iodinated contrast agent within 72 hours after administration of the study agent; * Is receiving cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs (with exception of low dose aspirin \[≤325 mg per day\]), aminoglycosides, or any other drugs that carry a significant risk of nephrotoxicity (in the opinion of the Investigator) during the time period beginning within 72 hours prior to contrast administration and up to 72 hours postdose; * Prior to, during or post the cardiac angiography, is receiving or will be receiving a prophylactic medication to prevent acute kidney injury that is not permitted by this protocol (e.g., theophylline, fenoldopam, etc.); * During cardiac angiography, is going to receive provocative pharmacological agents such as adenosine or dipyridamole; * Is planned to undergo major surgery (e.g. coronary artery bypass graft, valve surgery, etc.) within 48-72 hours after contrast administration; * Is planned to receive an intravenous diuretic or mannitol as prophylaxis to prevent acute renal injury (Note: chronic administration is allowed); * Is hemodynamically unstable within 48 hours pre-contrast administration defined as a systolic blood pressure \<90 mmHg or requires pressor or intra-aortic balloon support; * Has any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or postdose follow-up examinations; * Is determined by the Investigator that the patient is clinically unsuitable for the study Note: Changes in diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers doses within 72 hours prior to and up to 72 hours post contrast administration should be avoided unless clinically necessary for the subject's underlying medical condition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Contrast-induced Nephropathy (CIN) | 48 to 72 hours After Injection of Contrast Media | The number of participants who presented with CIN (defined as an increase in Serum Creatinine (SCr) from baseline greater than or equal to 0.5 mg/dL following the administration of iopamidol-370 or iodixanol 320 while undergoing cardiac angiography). Since CIN is a prospectively-defined outcome measure of the trial, patients experiencing CIN were not reported as having an adverse event. |
| Baseline and Change From Baseline Measurements for the One Participant With Contrast-Induced Nephropathy (CIN) at the 48 to 72 Hours After Injection of Contrast Media Visit | Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media | Only 1 participant presented with incidence of CIN (change from baseline greater than or equal to 0.5 mg/dL) following the administration of iopamidol-370 while undergoing cardiac angiography. The participant's measurements at baseline and at 48 to 72 hours after the injection of contrast agent, as well as the difference between the two, are displayed here. Since CIN is a prospectively-defined outcome measure of the trial, patients experiencing CIN were not reported as having an adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With a >=25% Decrease in Estimated Glomerular Filtration Rate (eGFR) | Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media | This outcome measure provides the total number of participants that had a decrease from baseline in eGFR greater or equal to 25% within 48 to 72 hours following the cardiac angiography procedure. |
| The Number of Participants With a >=25% Increase in Serum Creatinine (SCr) | Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media | This outcome measure provides the total number of participants that had a increase from baseline in SCr greater or equal to 25% within 48 to 72 hours following the cardiac angiography procedure. |
| Number of Participants Requiring Dialysis | 48 to 72 hours after injection of contrast media | This outcome measure provides the total number of participants requiring dialysis occurring from acute renal failure. |
| Number of Participants Who Died From Acute Renal Failure | Any timepoint (Screening [up to 72 hours prior to injection of contrast media], Baseline [just before injection], or 48 to 72 hours or 7 days after injection) | This outcome measure provides the total number of participants who died as a result of acute renal failure. |
Countries
United States
Participant flow
Recruitment details
This study was conducted in 4 investigational centers in China. The first subject was enrolled on 24 March 2009, and the last subject completed the study on 06 September 2009.
Pre-assignment details
Phase IV, multicenter, randomized, double-blind, parallel-group comparison of iopamidol-370 and iodixanol-320 in patients at high risk for CIN (patients with Stage 3 or 4 CKD \[men: SCr level of ≥1.5 mg/dL; women: ≥1.3 mg/dL or eGFR between 15 and 50 mL/min\]) & Diabetes mellitus who would undergo clinically indicated cardiac angiography procedures.
Participants by arm
| Arm | Count |
|---|---|
| Iopamiro-370 (Iopamidol injection at the 370 mgI/mL concentration) | 12 |
| Visipaque 320 (Iodixanol injection at the 320 mgI/mL concentration) | 11 |
| Total | 23 |
Baseline characteristics
| Characteristic | Iopamiro-370 | Visipaque 320 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment China | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Baseline and Change From Baseline Measurements for the One Participant With Contrast-Induced Nephropathy (CIN) at the 48 to 72 Hours After Injection of Contrast Media Visit
Only 1 participant presented with incidence of CIN (change from baseline greater than or equal to 0.5 mg/dL) following the administration of iopamidol-370 while undergoing cardiac angiography. The participant's measurements at baseline and at 48 to 72 hours after the injection of contrast agent, as well as the difference between the two, are displayed here. Since CIN is a prospectively-defined outcome measure of the trial, patients experiencing CIN were not reported as having an adverse event.
Time frame: Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iopamiro-370 | Baseline and Change From Baseline Measurements for the One Participant With Contrast-Induced Nephropathy (CIN) at the 48 to 72 Hours After Injection of Contrast Media Visit | Baseline | 1.10 milligrams per deciliter (mg/dL) |
| Iopamiro-370 | Baseline and Change From Baseline Measurements for the One Participant With Contrast-Induced Nephropathy (CIN) at the 48 to 72 Hours After Injection of Contrast Media Visit | 48 to 72 hours After Injection of Contrast Media | 1.60 milligrams per deciliter (mg/dL) |
| Iopamiro-370 | Baseline and Change From Baseline Measurements for the One Participant With Contrast-Induced Nephropathy (CIN) at the 48 to 72 Hours After Injection of Contrast Media Visit | Change from Baseline | 0.50 milligrams per deciliter (mg/dL) |
Primary
The Number of Participants With Contrast-induced Nephropathy (CIN)
The number of participants who presented with CIN (defined as an increase in Serum Creatinine (SCr) from baseline greater than or equal to 0.5 mg/dL following the administration of iopamidol-370 or iodixanol 320 while undergoing cardiac angiography). Since CIN is a prospectively-defined outcome measure of the trial, patients experiencing CIN were not reported as having an adverse event.
Time frame: 48 to 72 hours After Injection of Contrast Media
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iopamiro-370 | The Number of Participants With Contrast-induced Nephropathy (CIN) | 1 Participants |
| Visipaque 320 | The Number of Participants With Contrast-induced Nephropathy (CIN) | 0 Participants |
Secondary
Number of Participants Requiring Dialysis
This outcome measure provides the total number of participants requiring dialysis occurring from acute renal failure.
Time frame: 48 to 72 hours after injection of contrast media
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iopamiro-370 | Number of Participants Requiring Dialysis | 0 Participants |
| Visipaque 320 | Number of Participants Requiring Dialysis | 0 Participants |
Secondary
Number of Participants Who Died From Acute Renal Failure
This outcome measure provides the total number of participants who died as a result of acute renal failure.
Time frame: Any timepoint (Screening [up to 72 hours prior to injection of contrast media], Baseline [just before injection], or 48 to 72 hours or 7 days after injection)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iopamiro-370 | Number of Participants Who Died From Acute Renal Failure | 0 Participants |
| Visipaque 320 | Number of Participants Who Died From Acute Renal Failure | 0 Participants |
Secondary
The Number of Participants With a >=25% Decrease in Estimated Glomerular Filtration Rate (eGFR)
This outcome measure provides the total number of participants that had a decrease from baseline in eGFR greater or equal to 25% within 48 to 72 hours following the cardiac angiography procedure.
Time frame: Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iopamiro-370 | The Number of Participants With a >=25% Decrease in Estimated Glomerular Filtration Rate (eGFR) | 1 Participants |
| Visipaque 320 | The Number of Participants With a >=25% Decrease in Estimated Glomerular Filtration Rate (eGFR) | 0 Participants |
Secondary
The Number of Participants With a >=25% Increase in Serum Creatinine (SCr)
This outcome measure provides the total number of participants that had a increase from baseline in SCr greater or equal to 25% within 48 to 72 hours following the cardiac angiography procedure.
Time frame: Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iopamiro-370 | The Number of Participants With a >=25% Increase in Serum Creatinine (SCr) | 1 Participants |
| Visipaque 320 | The Number of Participants With a >=25% Increase in Serum Creatinine (SCr) | 0 Participants |