E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with moderate (eGFR 30 – 59 mL/min/1.73 m2) to severe renal impairment (eGFR < 30 mL/min/1.73 m2) scheduled to undergo contrast-enhanced MRI with Primovist/Eovist. |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to severe renal impairment. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038469 |
E.1.2 | Term | Renal impairment NOS |
E.1.2 | System Organ Class | 100000004857 |
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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 |
The primary objective is to assess the magnitude of potential risk of developing NSF with the administration of Primovist/Eovist in patients with moderate to severe renal impairment for the development of NSF, based on diagnostically specific clinical and histopathological information. |
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E.2.2 | Secondary objectives of the trial |
•to assess the magnitude of the potential risk of developing cutaneous symptoms consistent with NSF with the administration of Primovist/Eovist in patients with moderate to severe renal impairment for the development of cutaneous symptoms consistent with NSF, based on specific clinical information for patients in whom biopsy is not available
•to evaluate the confidence of the investigator to make a diagnosis based on the Primovist/Eovist enhanced MRI
•to determine imaging efficacy by qualitatively evaluating the parameters “lesion detection”, “lesion delineation” and “lesion characterization”.
•to evaluate the number and characteristics of adverse events reported in association with the administration of Primovist/Eovist.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patient must be scheduled for CE-MRI OF THE LIVER with Primovist/Eovist based on careful risk/benefit evaluation at the recommended dose in one of the approved indications
•Patient must fulfill criteria for moderate (eGFR 30 – 59 mL/min/1.73 m2) to severe (eGFR < 30 mL/min/1.73 m2) renal impairment. Patients will initially be qualified using the simplified MDRD formula, based on a determination of serum creatinine within 6 weeks prior to the administration of Primovist/Eovist. Final patient stratification will be based on the complete MDRD formula (13) based on age, gender, ethnicity; and on serum creatinine, serum urea nitrogen, and serum albumin concentration as measured within 24h prior to Primovist/Eovist administration.
•Patient must sign study-specific informed consent.
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E.4 | Principal exclusion criteria |
•GBCA-enhanced MRI (or administration of a GBCA for any other CE imaging procedure) other than Primovist/Eovist within 12 months prior to administration of Primovist/Eovist
-Rationale for selected time window: to minimize level of confounding from prior administration of GBCA for the estimation of risk of NSF for Primovist/Eovist while at the same time avoiding the elimination of too many potential participants from the study.
-Exposure to GBCA within 12 months prior to administration of Primovist/Eovist will be determined at the time of the initial evaluation via history (elicited from patient) and review of patient’s medical records, if available at that time. Subsequently, a more thorough analysis of the patient’s medical records will be carried out to ascertain the accuracy of the GBCA exposure information obtained at the time of the ÌNITIAL EVALUATION
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point of the study is the number of patients with moderate to severe renal impairment who develop NSF, based on diagnostically specific clinical and histopathological information, following the administration of Primovist/Eovist injection within the 2-year follow-up period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Number of patients with moderate to severe renal impairment in whom no biopsy was obtained who develop NSF based on diagnostically specific clinical information. The clinical findings related to NSF will be summarized by clinical score.
• Confidence of the investigator to make a diagnosis based on the Primovist/Eovist enhanced MRI.
• Number and characteristics of adverse events reported in association with the administration of Primovist/Eovist.
• Number of patients with “Excellent / Good / Adequate / Insufficient” scores for “lesion detection”, “lesion delineation” and “lesion characterization.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Austria |
Germany |
Italy |
Korea, Republic of |
Spain |
Thailand |
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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End of the trial is the Last Patient Last Visit date |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |