A Study to Explore the Renal Safety of Visipaque Injection 320 mgI/mL in Patients With Chronic Kidney Disease

Study Overview
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Brief Summary
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This parallel-group, randomized, placebo-controlled study will examine the incidence and severity of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) stage III/IV following an i.v. injection of iso-osmolar iodinated contrast material iodixanol (Visipaque™ Injection 320 mgI/mL), as compared with patients who received saline and underwent a non-enhanced CT (NECT) and duplex ultrasound (US) during their scheduled post-EVAR surveillance imaging.

Detailed Description
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GEHC has decided not to provide this detail

Official Title
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Parallel-Group, Placebo-Controlled Randomized Study Investigating the Effect of Intravenous Iso-osmolar Iodinated Contrast Material Iodixanol (Visipaque™ Injection 320 mgI/mL) on Renal Function in Adults With Chronic Kidney Disease (CKD) Stage III or Stage IV Who Have Undergone Endovascular Aneurysm Repair (EVAR)

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Drug: Visipaque
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Was ≥18 years of age at the time that written informed consent is obtained. Was male or is a nonpregnant, nonlactating female who is either surgically sterile or is postmenopausal. Women of childbearing potential must use adequate contraception from Screening until 30 days after the Baseline Visit and must have a negative pregnancy test at the Baseline Visit. Was an outpatient who has undergone successful EVAR and is scheduled for his/her next post-procedural imaging follow-up examination. Had previously completed one or more of his or her post-EVAR surveillance imaging examination(s) that provided evidence on stable post-EVAR status. Had a documented diagnosis of stage III or IV CKD and stable renal function. Was able to provide written informed consent. Was able and willing to comply with all study procedures as described in the protocol. Exclusion Criteria: Was pregnant, lactating, is possibly pregnant, or is actively trying to conceive during the study period. Was a patient for whom an endoleak or other clinically meaningful EVAR-related complication (as judged by the investigator) has already been discovered. Was undergoing surveillance following a Thoracic Endovascular Repair (TEVAR). Had a known or suspected history of immediate or delayed hypersensitivity to iodine or any iodinated contrast medium. Was using metformin (e.g., Glucophage®) that cannot be discontinued for the period of 24 hours prior to the Baseline Visit and for at least 48 hours after the imaging procedure. Had been exposed to any intravascular iodinated contrast medium in the 7 days prior to the Baseline Visit. Had congestive heart failure (New York Heart Association [NYHA] Class IV) or hepatic failure/liver cirrhosis. Had Stage V CKD. Had a pre-existing requirement for renal dialysis. Had undergone percutaneous transluminal renal angioplasty (PTRA) within 12 months before the index EVAR procedure or is scheduled to undergo PTRA during the study period. Had any clinically active, serious, life-threatening disease, medical, or significant psychiatric condition; has a life expectancy of less than 6 months; or is, in the Investigator's opinion, unsuitable for participation in the study for any reason. Had been enrolled in another clinical study within the 30 days prior to the Screening Visit or is planned to enroll in another clinical study within the duration of this study. Had been previously enrolled in this study. Was using i.v. vasopressor or inotropic medications. Had used nonsteroidal anti-inflammatory drugs (NSAIDs) or any nephrotoxic medication within 48 hours of the Baseline Visit or will do so within 72 hours after the CT procedure-with the exception of acetylsalicylic acid (Aspirin) at a dose of ≤100 mg daily (QD). Had been hospitalized within 30 days prior to Screening Visit for any reason other than practical purposes for management of tests or diagnostic assessments.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Visipaque™: Contrast-Enhanced Computed Tomography (CECT)<br>Participants received 1 intravenous injection of Visipaque™ 320 mg I/ml injection (100 mL iodixanol) and underwent computed tomography (CT) examination. | Drug: Visipaque<br>* 100 mL iodixanol (Visipaque Injection 320 mg I/mL), followed by a 10 mL saline flush to ensure delivery of the full dose of Visipaque.<br>|
| Placebo Comparator: Saline: Non-Enhanced Computed Tomography (NECT)<br>Participants received 1 intravenous injection of saline placebo (matched to Visipaque™ 320 mg I/ml injection) and underwent computed tomography (CT) examination and supplemental non-contrast duplex ultrasonography imaging examination. | Drug: Placebos<br>* 100 mL saline, followed by a 10 mL saline flush.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the Incidence of Acute Kidney Injury (AKI) Stage >=1 Per Acute Kidney Injury Network (AKIN) Serum Creatinine (SCr) Criteria | AKIN Serum Creatinine Criteria for AKI- Stage 1: a SCr increase of >=0.3 mg/dL (>=26.4 μmol/L) or increase to >=150% to 200% (>=1.5- to 2.0-fold) from baseline within 48 hours. Stage 2: a SCr increase to >200% to 300% (>2.0- to 3-fold) from baseline within 48 hours. Stage 3: a SCr increase to >300% (>3.0-fold) from baseline or SCr >=4.0 mg/dL (>=354 μmol/L) with an acute increase of >=0.5 mg/dL (>=44 μmol/L) within 48 hours. | 48 hours post-baseline (Follow-up 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the Incidence of Acute Kidney Injury (AKI) Stage >=2 Per Acute Kidney Injury Network (AKIN) Serum Creatinine (SCr) Criteria | AKIN Serum Creatinine Criteria for AKI- Stage 1: a SCr increase of >=0.3 mg/dL (>=26.4 μmol/L) or increase to >=150% to 200% (>=1.5- to 2.0-fold) from baseline within 48 hours. Stage 2: a SCr increase to >200% to 300% (>2.0- to 3-fold) from baseline within 48 hours. Stage 3: a SCr increase to >300% (>3.0-fold) from baseline or SCr >=4.0 mg/dL (>=354 μmol/L) with an acute increase of >=0.5 mg/dL (>=44 μmol/L) within 48 hours. | 48 hours post-baseline (Follow-up 1) | 
| Assessment of the Incidence of Acute Kidney Injury (AKI) by Contrast Induced Nephropathy (CIN) | Standard definition of CIN: Increase in SCr of 0.5 mg/dL or more in the 24 to 72 hours after the CT scan. | 48 hours post-baseline (Follow-up 1) | 
| Assessment of the Incidence of Acute Kidney Injury (AKI) Stage >=2 By Waikar Criteria | Waikar's definitions of AKI: Stage 1: 0.3 mg/dL increase in SCr over 24 hours or a 0.5 mg/dL increase in SCr over 48 hours. Stage 2: 0.5 mg/dL increase in SCr over 24 hours or a 1.0 mg/dL increase in SCr over 48 hours. Stage 3: 1.0 mg/dL increase in SCr over 24 hours or a 1.5 mg/dL increase in SCr over 48 hours. | 48 hours post-baseline (Follow-up 1) | 
| All Cause Mortality and Morbidity | Mortality (all cause death) and morbidity i.e. critical events. | From Baseline to Month 6 | 
| Blinded Independent Assessment of Image Quality/Diagnostic Confidence Using a 5-Point Scale | Blinded independent assessment of image quality/diagnostic confidence using a 5-point scale. Image quality/diagnostic confidence for all imaging studies was rated on a 5-point scale from 1 (poor) to 5 (excellent). | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute kidney injury (AKI), Acute kidney injury network (AKIN), Chronic kidney disease (CKD), Contrast-enhanced computed tomography (CECT), Endovascular Aneurysm Repair (EVAR), Iodixanol, Non-enhanced computed tomography (NECT), Serum creatinine (SCr)