Clinical trial NCT00782639: Renal Safety of Iopamidol Versus Iodixanol During Coronary Angiography in Diabetic Patients
Official title: RECARE (REnal Safety Following the Intra-Arterial Administration of Iopamidol vs. Iodixanol During Coronary AngiogRaphy in DiabEtic Patients)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Renal Impairment
Diabetes Mellitus
Lead sponsor: Bracco Diagnostics, Inc
Sponsor class: INDUSTRY
First posted: 2008-10-31
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants With Contrast-induced Nephropathy (CIN)
timeFrame: 48 to 72 hours After Injection of Contrast Media
measure: 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
timeFrame: Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media
Secondary outcomes:
measure: The Number of Participants With a >=25% Decrease in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media
measure: The Number of Participants With a >=25% Increase in Serum Creatinine (SCr)
timeFrame: Baseline (just prior to injection of contrast media) and 48 to 72 hours after injection of contrast media
measure: Number of Participants Requiring Dialysis
timeFrame: 48 to 72 hours after injection of contrast media
measure: Number of Participants Who Died From Acute Renal Failure
timeFrame: 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)
Other outcomes:
Locations:
city: Princeton
country: United States
facility: Bracco Diagnostics Inc.
state: New Jersey
Study officials:
affiliation: Bracco Diagnostics
name: Alberto Spinazzi, M.D.
role: STUDY_CHAIR
References: