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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: Visipaque; Drug: Placebos

Detailed Description

GEHC has decided not to provide this detail

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Montreal, Canada, H2X 0A9
    • CRCHUM- CHUM Research Center
  • Winnipeg, Canada, R2H 2A6
    • St. Boniface General Hospital
• Poland
  • Bytom, Poland, 41-902
    • Oddzial Chirurgii Naczyniowej i Ogolnej, Wojewodzki Szpital Specjalistyczny Nr 4 w Bytomiu
  • Gdansk, Poland, 80-952
    • Klinika Kardiochirurgii i Chirurgii Naczyniowej, Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-081
    • Klinika Chirurgii Naczyniowej i Angiologii, Samodzielny Publiczny Szpital Kliniczny nr 1
  • Poznan, Poland, 61-848
    • Oddzial Chirurgii Ogolnej i Naczyn, Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Cadiz, Spain, 11009
    • Hospital Universitario Puerta Del Mar
  • Palma, Spain, 07120
    • Hospital Universitario Son Espases
• United Kingdom
  • London, United Kingdom, SW17 0QT
    • St. George's Healthcare NHS Trust, St. George's Hospital
  • Stoke on Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital, Radiology Department
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University Hospital
  • Arizona
    • Mesa, Arizona, United States, 85210
      • : Aventiv Research Inc.
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Central Arkansas Veteran's Healthcare System
  • California
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
  • Florida
    • Doral, Florida, United States, 33166
      • Universal Axon Clinical Research, LLC
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Tampa, Florida, United States, 33606
      • University of South Florida - South Tampa Campus
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center/Boston Medical Center
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • The Duluth Clinic, Ltd.
  • New York
    • New York, New York, United States, 10019
      • Mount Sinai West
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill Clinical Translational Research Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Visipaque™: Contrast-Enhanced Computed Tomography (CECT); Participants received 1 intravenous injection of Visipaque™ 320 mg I/ml injection (100 mL iodixanol) and underwent computed tomography (CT) examination.	Drug: Visipaque; 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.
Placebo Comparator: Saline: Non-Enhanced Computed Tomography (NECT); 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; 100 mL saline, followed by a 10 mL saline flush.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GE Healthcare
• Collaborators: Syneos Health

Publications and helpful links

General Publications

• Solomon R. PRESERVE: The End or the Beginning of a New Era in Prevention of Contrast-Associated Acute Kidney Injury? Am J Kidney Dis. 2018 Sep;72(3):322-324. doi: 10.1053/j.ajkd.2018.03.013. Epub 2018 May 8. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Actual): September 13, 2018
• Study Completion (Actual): October 19, 2018

Study Registration Dates

• First Submitted: March 21, 2017
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: November 28, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Iodixanol; Chronic kidney disease (CKD); Contrast-enhanced computed tomography (CECT); Acute kidney injury (AKI); Acute kidney injury network (AKIN); Endovascular Aneurysm Repair (EVAR); Non-enhanced computed tomography (NECT); Serum creatinine (SCr)
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: GE-012-106; 2016-001668-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No