Multicenter, Open-label Study to Evaluate the Safety and Efficacy (by Blinded Reading) of Contrast-Enhanced Magnetic Resonance Angiography (MRA) After a Single Intravenous Injection of 0.1 mmol/kg Gadobutrol in Subjects With Known or Suspected Vascular Disease of the Supra-aortic Vessels
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 479
- 主要终点
- Sensitivity for Detection of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA
研究概览
简要总结
Subjects referred for a routine CTA (computed tomography angiography) or MRA (magnetic resonance angiography) will be invited to participate in the study and subjects will be involved in the study for between 2 and 12 days. Two to three visits to the study doctor will be required.
This study will compare the diagnostic results of Gadobutrol enhanced MRA images with MRA images taken without contrast agent using images from a CTA as the standard of reference, which may have been performed up to 60 days prior to enrolment. If a CTA has not been performed in this prior time period, a CTA is required for the study.
MRA and CTA images will be collected for an independent review (blinded read).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects, aged 18 years and older
- •Any of the following:
- •Known or suspected supra-aortic arterial disease based on:
- •Prior stroke
- •Transient ischemic attack (TIA)
- •Amaurosis Fugax (transient monocular blindness)
- •Referred for evaluation of any supra-aortic vessel (for clinically significant stenosis)
- •Follow-up for a stent in a supra-aortic vessel
- •Prior imaging study (CTA or ultrasound) showing ≥ 50% stenosis of a supra-aortic vessel segment (within 60 days before consent). The proportion of subjects with positive disease (determined by the investigator, based on CTA or ultrasound) will be monitored during the study, and enrolment may be further restricted to require ≥ 70% stenosis to ensure that overall there are an adequate number of subjects with clinically significant disease for the evaluation of study endpoints.
- •Willingness to undergo the routine Contrast Enhanced Magnetic Resonance Angiography [CE MRA] examination with gadobutrol
- •Willingness and ability to follow directions and complete all study procedures specified in the protocol
- •Females of childbearing potential only: Negative pregnancy test on the day of the MRA before the administration of study drug
排除标准
- •Pregnant or nursing (including pumping for storage and feeding)
- •Received any other investigational product or participation in any other clinical trial within 30 days before enrollment into this study
- •Previous enrollment into this study or into any other Bayer sponsored study using gadobutrol
- •Contraindication to the MRA examinations (e.g. inability to hold breath; severe arrhythmias; very low cardiac output, severe claustrophobia, defibrillators or other metallic devices not approved for MRI)
- •Contraindication to the use of Gd-containing contrast agents (including subjects with suspicion for or known to have Nephrogenic Systemic Fibrosis [NSF])
- •History of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents
- •Received any contrast agent within 72 hours before the study MRA, or scheduled receipt of any contrast agent within 24 hours after the study MRA (Note: This applies also to a CTA potentially scheduled during the course of the study.)
- •Estimated glomerular filtration rate (eGFR) value < 30 ml/min/1.73 m2 derived from a serum creatinine result within 2 weeks before the gadobutrol injection. Any subject on hemodialysis or peritoneal dialysis is excluded from participation. Use the value obtained prior to and closest to the time of the MRA, if there are multiple creatinine values. (Do not use the core lab value if not available prior to the MRA.)
- •Acute renal insufficiency of any intensity, either due to hepato-renal syndrome or occurring in the peri-operative liver transplantation period
- •Severe cardiovascular disease (e.g. acute myocardial infarction [< 14 days], unstable angina, congestive heart failure New York Heart Association class IV) or known long QT syndrome
- •Suspected clinical instability or unpredictability of the clinical course during the study period (e.g. due to previous surgery)
- •Scheduled or potentially expected for the period between the CTA and gadobutrol MRA:
- •Any procedure that may alter the MRA or CTA interpretation, or
- •Any interventional or surgical procedure involving the supra-aortic vessels
研究组 & 干预措施
Arm 1
干预措施: Gadobutrol (Gadovist, BAY86-4875) (Drug)
结局指标
主要结局
Sensitivity for Detection of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA
时间窗: Images were taken pre-injection and post-injection
Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded, as assessed by the standard of reference (SoR) (computed tomographic angiography \[CTA\]; blinded readers). This was determined using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. In case of multiple stenosis in any one segment, the most severe stenosis in the segment was recorded.
Specificity for Exclusion of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA
时间窗: Images were taken pre-injection and post-injection
Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded, as assessed by the SoR (CTA; blinded readers). This was determined using the NASCET criteria. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. In case of multiple stenosis in any one segment, the most severe stenosis in the segment was recorded.
Minimum Gadobutrol Performance for Sensitivity: Sensitivity > 50%
时间窗: Images were taken pre-injection and post-injection
Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded as assessed by the SoR (CTA; blinded readers). For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. Gadobutrol minimum performance criteria was based on a stenosis of 50% calculated from the native vessel diameter.
Minimum Gadobutrol Performance for Specificity: Specificity > 50%
时间窗: Images were taken pre-injection and post-injection
Clinically significant disease was defined as 70 to 99% stenosis of a segment, but not occluded as assessed by the SoR (CTA; blinded readers). For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. Gadobutrol minimum performance criteria was based on a stenosis of 50% calculated from the native vessel diameter.
Percentage of Assessable Vascular Segments Using Gadobutrol-Enhanced MRA and Unenhanced MRA
时间窗: Images were taken pre-injection and post-injection
Each vascular segment was visualized using unenhanced MRA and gadobutrol-enhanced MRA, characterized by the on-site investigators, three independent blinded readers (BR) (BR 1, BR 2 and BR 3) and majority readers (the outcome determined by at least two of the blinded readers). A segment was assessable if it was visualized along its entire length and if any region of stenosis, was measured reliably. There were 21 segments of the supra-aortic arteries assessed per participant.
次要结局
- Types of Artifacts on a Segment Basis by Blinded Reader 1(Images were taken pre-injection and post-injection)
- Length of Stenosis (>=70%) in the Proximal Segments Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA(Images were taken pre-injection and post-injection)
- Types of Artifacts on a Segment Basis by Blinded Reader 2(Images were taken pre-injection and post-injection)
- Types of Artifacts on a Segment Basis by Blinded Reader 3(Images were taken pre-injection and post-injection)
- The Percentage of Location of Stenosis (>=70%) in the Proximal Segments Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA(Images were taken pre-injection and post-injection)
- Type of Secondary Radiologic Indicators for Diagnosis of Clinically Relevant Disease(Images were taken pre-injection and post-injection)
- Diagnostic Confidence by the Blinded Readers Using Gadobutrol-Enhanced MRA and Unenhanced MRA(Images were taken pre-injection and post-injection)
- Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images - Blinded Reader 1(Images were taken pre-injection and post-injection)
- Vessel Diameter (Millimeter [mm]) at the Normal Point and the Narrowest Point in Gadobutrol-Enhanced MRA, Unenhanced MRA and CTA Images(Images were taken pre-injection and post-injection)
- Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images - Blinded Reader 2(Images were taken pre-injection and post-injection)
- Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images - Blinded Reader 3(Images were taken pre-injection and post-injection)
- Types of Additional Imaging Studies Recommended by the Clinical Investigator After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images(Images were taken pre-injection and post-injection)
- The Percentage of Segments With Artifacts Presence(Images were taken pre-injection and post-injection)
- The Percentage of Presence of Secondary Radiologic Indicators for Diagnosis of Clinically Relevant Disease(Images were taken pre-injection and post-injection)
- The Percentage of Participants With Additional Imaging Studies Recommended by the Blinded Readers and the Clinical Investigator After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images(Images were taken pre-injection and post-injection)