Chronic Kidney Diseases
Conditions
Keywords
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)
Brief summary
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
GEHC has decided not to provide this detail
Interventions
DRUGVisipaque
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.
DRUGPlacebos
100 mL saline, followed by a 10 mL saline flush.
Sponsors
Syneos Health
GE Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the Incidence of Acute Kidney Injury (AKI) Stage >=1 Per Acute Kidney Injury Network (AKIN) Serum Creatinine (SCr) Criteria | 48 hours post-baseline (Follow-up 1) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the Incidence of Acute Kidney Injury (AKI) Stage >=2 Per Acute Kidney Injury Network (AKIN) Serum Creatinine (SCr) Criteria | 48 hours post-baseline (Follow-up 1) | 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. |
| Assessment of the Incidence of Acute Kidney Injury (AKI) by Contrast Induced Nephropathy (CIN) | 48 hours post-baseline (Follow-up 1) | Standard definition of CIN: Increase in SCr of 0.5 mg/dL or more in the 24 to 72 hours after the CT scan. |
| Assessment of the Incidence of Acute Kidney Injury (AKI) Stage >=2 By Waikar Criteria | 48 hours post-baseline (Follow-up 1) | 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. |
| All Cause Mortality and Morbidity | From Baseline to Month 6 | Mortality (all cause death) and morbidity i.e. critical events. |
| Blinded Independent Assessment of Image Quality/Diagnostic Confidence Using a 5-Point Scale | Month 6 | 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). |
Countries
Belgium, Canada, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
The Study was conducted at 29 sites in United States of America & Europe from 8 February 2018 to 19 October 2018. A total of 4 participants with Chronic Kidney Disease (CKD) stage III/IV were enrolled in the study.
Pre-assignment details
Participants were randomized in 1:1 ratio to undergo either contrast-enhanced computed tomography (CECT) or non-enhanced computed tomography (NECT), of which 1 participant withdrew from study.
Participants by arm
| Arm | Count |
|---|---|
| Visipaque™: Contrast-Enhanced Computed Tomography (CECT) Participants received 1 intravenous injection of Visipaque™ 320 mg I/ml injection (100 mL iodixanol) and underwent CT examination. | 2 |
| Saline: Non-Enhanced Computed Tomography (NECT) Participants received 1 intravenous injection of saline placebo (matched to Visipaque™ 320 mg I/ml injection) and underwent CT examination and supplemental non-contrast duplex ultrasonography imaging examination. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Visipaque™: Contrast-Enhanced Computed Tomography (CECT) | Saline: Non-Enhanced Computed Tomography (NECT) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 1 / 2 | 0 / 2 |
Outcome results
Primary
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.
Time frame: 48 hours post-baseline (Follow-up 1)
Population: Data were not collected, as planned analysis could not be performed due to early study termination.
Secondary
All Cause Mortality and Morbidity
Mortality (all cause death) and morbidity i.e. critical events.
Time frame: From Baseline to Month 6
Population: Data were not collected, as planned analysis could not be performed due to early study termination.
Secondary
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.
Time frame: 48 hours post-baseline (Follow-up 1)
Population: Data were not collected, as planned analysis could not be performed due to early study termination.
Secondary
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.
Time frame: 48 hours post-baseline (Follow-up 1)
Population: Data were not collected, as planned analysis could not be performed due to early study termination.
Secondary
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.
Time frame: 48 hours post-baseline (Follow-up 1)
Population: Data were not collected, as planned analysis could not be performed due to early study termination.
Secondary
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).
Time frame: Month 6
Population: Data were not collected, as planned analysis could not be performed due to early study termination.