E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the safety of intravenous (i.v.) iodinated iso-osmolar iodixanol (Visipaque™ Injection 320 mgI/mL) usage in contrast-enhanced computed tomography (CECT) for CKD stage III/IV patients by evaluating the incidence of acute kidney injury (AKI) stage ≥1, per acute kidney injury network (AKIN) serum creatinine (SCr) criteria [AKIN 2015] [Mehta et al. 2007], in patients undergoing CECT with iodixanol vs patients receiving placebo and undergoing nonenhanced computed tomography (NECT) and an additional non–contrast-enhanced ultrasound imaging modality. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the safety of i.v. iodinated iso-osmolar iodixanol (Visipaque™ Injection 320 mgI/mL) usage in CECT for CKD stage III/IV patients by evaluating
- of the incidence AKI stage ≥2, per AKIN SCr criteria [AKIN 2015] [Mehta et al. 2007], in patients undergoing CECT with iodixanol vs patients receiving placebo and undergoing NECT and an additional non–contrast-enhanced ultrasound imaging modality.
- incidence of AKI by other definitions (standard definition of contrast induced nephropathy (CIN) [Mehran and Nikolsky 2006], and AKI stages ≥2 by Waikar criteria [Waikar and Bonventre 2009]) in patients undergoing CECT with iodixanol vs patients receiving placebo and undergoing NECT and an additional non–contrast-enhanced ultrasound imaging modality.
- mortality and morbidity within 6 months of intervention in patients undergoing CECT with iodixanol vs. patients receiving placebo and undergoing NECT and an additional non–contrast-enhanced ultrasound imaging modality. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Is ≥18 years of age at the time that written informed consent is obtained.
(2) Is male or is a nonpregnant, nonlactating female who is either surgically sterile (has a documented bilateral tubal ligation or oophorectomy and/or documented hysterectomy) or is postmenopausal (cessation of menses for more than 1 year). Women of childbearing potential must use adequate contraception from Screening until 30 days after the Baseline Visit and must have a negative result for a urine human chorionic gonadotropin pregnancy test at the Baseline Visit.
(3) Is an outpatient who has undergone successful EVAR and is scheduled for his/ her next post-procedural imaging follow-up examination.
(4) Has previously completed one or more of his or her first post-EVAR surveillance imaging examination(s) that provided evidence on stable post-EVAR status.
(5) Has a documented diagnosis of stage III or IV (defined as 30≤ estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and 15 ≤eGFR <30 mL/min/1.73 m², respectively, according to the Modification of Diet in Renal Disease [MDRD] equation) CKD and stable renal function (last 2 SCr values within ±0.5 mg/dL of each other, with the most recent value within 14 days prior to the scheduled CT examination and the preceding value within 1 to 12 months before that).
(6) Is able to provide written informed consent.
(7) Is able and willing to comply with all study procedures as described in the protocol.
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E.4 | Principal exclusion criteria |
(1) Is pregnant, lactating, is possibly pregnant, or is actively trying to conceive during the study period.
(2) Is a patient for whom an endoleak or other clinically meaningful EVAR-related complication (as judged by the Investigator) has already been discovered.
(3) Is a patient who is undergoing surveillance following a Thoracic Endovascular Repair (TEVAR)
(4) Has a known or suspected history of immediate or delayed hypersensitivity (including but not limited to hives, anaphylactoid or cardiovascular reactions, laryngeal edema, and bronchospasm) to iodine or any iodinated contrast medium.
(5) Is using metformin (e.g., Glucophage®) that cannot be discontinued for the period of 48 hours prior to the Baseline Visit and for at least 48 hours after the imaging procedure (renal function must be evaluated before metformin is resumed).
(6) Has been exposed to any intravascular iodinated contrast medium in the 14 days prior to the Baseline Visit.
(7) Has congestive heart failure (New York Heart Association [NYHA] Class IV) or hepatic failure/liver cirrhosis according to the investigator’s judgement.
(8) Has stage V CKD, defined as eGFR <15 mL/min/1.73 m² according to the MDRD equation.
(9) Has a pre-existing requirement for renal dialysis.
(10) Has undergone percutaneous transluminal renal angioplasty (PTRA) within 12 months before the index EVAR procedure or is scheduled to undergo PTRA during the study period.
(11) Has 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.
(12) Has 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.
(13) Has been previously enrolled in this study.
(14) Is using i.v. vasopressor or inotropic medications.
(15) Has 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 (renal function must be evaluated before any nephrotoxic medication is resumed) – with the exception of acetylsalicylic acid (Aspirin) at a dose of ≤100 mg daily (QD).
(16) Has been hospitalized within 30 days prior to Screening Visit for any reason other than practical purposes for management of tests or diagnostic assessments.
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of AKI stage ≥1 (AKIN SCr criteria) following an i.v. injection of iodinated iso-osmolar contrast material iodixanol (Visipaque™ Injection 320 mgI/mL) or saline in patients with CKD stage III/IV assessed at 48 hours post-baseline (Follow-up 1). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Incidence of AKI stage ≥1 (AKIN SCr criteria) at 48 hours post-baseline (Follow-up 1) |
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E.5.2 | Secondary end point(s) |
Incidence of AKI stage ≥2 (by AKIN SCr criteria) following an i.v. injection of iodinated iso-osmolar contrast material iodixanol (Visipaque™ Injection 320 mgI/mL) or saline in patients with CKD stage III/IV assessed at 48 hours post-baseline (Follow-up 1).
• Incidence of AKI (by standard definition of CIN [Mehran and Nikolsky 2006]) following an i.v. injection of iodinated iso-osmolar contrast material iodixanol (Visipaque™ Injection 320 mgI/mL) or saline in patients with CKD stage III/IV assessed at 48 hours post-baseline (Follow-up 1).
• Incidence of AKI stage ≥2 (by Waikar criteria [Waikar and Bonventre 2009]) following i.v. administration of iodinated iso-osmolar contrast material iodixanol (Visipaque™ Injection 320 mgI/mL) or saline in patients with CKD stage III/IV assessed at 48 hours post-baseline (Follow-up 1).
• Mortality and morbidity (i.e. critical events, including EVAR-related post-baseline events, as adjudicated by the CEAC) assessed at 6 months (Follow-up 3) in patients with CKD stage III/IV.
• Blinded independent assessment of image quality/diagnostic confidence using a 5-point scale.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Incidence of AKI stage ≥2 (by AKIN SCr criteria)
at 48 hours post-baseline (Follow-up 1).
- Incidence of AKI (by standard definition of CIN [Mehran and Nikolsky 2006]) at 48 hours post-baseline (Follow-up 1)
- Incidence of AKI stage ≥2 (by Waikar criteria [Waikar and Bonventre 2009]) at 48 hours post-baseline (Follow-up 1)
- Mortality and morbidity
assessed at 6 months (Follow-up 3) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
Germany |
Hungary |
Italy |
Netherlands |
New Zealand |
Poland |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |