Renal Safety of Iopamidol Versus Iodixanol During Coronary Angiography in Diabetic Patients
Renal Safety of Iopamidol Versus Iodixanol During Coronary Angiography in Diabetic Patients
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.
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.
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.