Gadobutrol Enhanced MRA of the Renal Arteries

Renal Artery Obstruction Clinical Trial

— GRAMS  

Official title:

Multicenter, Open-label Study to Evaluate the Safety and Efficacy (by Blinded Reading) of Gadobutrol-enhanced Magnetic Resonance Angiography (MRA) After a Single Injection of 0.1 mmol/kg of Gadobutrol in Subjects With Known or Suspected Renal Artery Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01344460
• Other study ID #: 91759
• Secondary ID: 2010-023002-13
• Status: Completed
• Phase: Phase 3
• First received: April 5, 2011
• Last updated: July 29, 2015
• Start date: May 2011
• Est. completion date: July 2012

Study information

• Verified date: July 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Ministry of HealthAustria: Federal Office for Safety in Health CareBrazil: Ministry of HealthChina: Food and Drug AdministrationColombia: National Institute of HealthCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesKorea: Food and Drug AdministrationPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSwitzerland: SwissmedicTaiwan: Department of HealthTurkey: Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 317
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female subjects, aged = 18 years

• Known or suspected renal artery disease based on any of the following:

• Referred for evaluation of the renal arteries for clinically significant stenosis

• Follow-up for a metallic stent in a renal artery

• Prior imaging study (CTA) showing = 50% renal artery stenosis (within 60 days prior to consent)

• Willingness to undergo the routine Contrast Enhanced Magnetic Resonance Angiography (CE MRA) examinations 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 prior to administration of study drug.

• Written informed consent (IC), including information about the provisions of the Health Insurance Portability and Accountability Act (HIPAA) as applicable.

Exclusion Criteria:

• 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 enrolment 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 Nefrogenic 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Renal Artery Obstruction

Intervention

Drug:
• Gadobutrol (Gadovist, BAY86-4875)
a single bolus injection of approx. 0.1mmol/kg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Colombia,  Czech Republic,  France,  Germany,  Korea, Republic of,  Poland,  Switzerland,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Assessable Vascular Segments Using Gadobutrol-Enhanced MRA and Unenhanced MRA	Each vascular segment was visualized using unenhanced MRA and gadobutrol-enhanced MRA, characterized by the on-site investigators, three independent blinded readers (reader 1, 2 and 3) and majority readers (the outcome determined by at least two of the blinded readers). The segments were predefined to standardize the blinded reader evaluations. A segment was assessable if it was visualized along its entire length and if any region of stenosis, was measured reliably. There were 6 segments assessed per participant (3 segments in the right renal artery and 3 segments in the left renal artery) and up to 9 segments in participants with renal transplant.	Images were taken pre-injection and post-injection	No
Primary	Sensitivity for Detection of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA	Clinically significant disease was defined as 50 to 99 percent (%) stenosis of a segment, but not occluded as assessed by the SoR. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease.	Images were taken pre-injection and post-injection	No
Primary	Specificity for Exclusion of Clinically Significant Disease Using Gadobutrol-Enhanced MRA and Unenhanced MRA	Clinically significant disease (stenosis) was defined as 50 to 99 percent (%) stenosis of a segment, but not occluded as assessed by the SoR. For each segment, the most severe stenosis/narrowing was identified and considered for the evaluation of clinically significant disease. Specificity = percentage of participants for which the imaging modalities (unenhanced or gadobutrol-enhanced) in the detection and exclusion of clinically significant stenosis.	Images were taken pre-injection and post-injection	No
Primary	Minimum Gadobutrol Performance for Sensitivity: Sensitivity More Than (>) 50%	Clinically significant disease was defined as >50% stenosis of a segment, but not occluded as assessed by the SoR. 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.	Images were taken pre-injection and post-injection	No
Primary	Minimum Gadobutrol Performance for Specificity: Specificity > 50%	Clinically significant disease (stenosis) was defined as >50% stenosis of a segment, but not occluded as assessed by the SoR. 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.	Images were taken pre-injection and post-injection	No
Secondary	Length of the Right and Left Renal Arteries Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA - Blinded Reader	The length of the left and right renal arteries were measured from the origin at the aorta to the bifurcation into the upper and lower pole arteries or the most distal point of the renal artery which could be visualized. This distal margin was the point where the diameter was still assessable. If there were more than 2 distal branches then the first large branch that was the dominant supply to a renal pole was used as the distal point.	Images were taken pre-injection and post-injection	No
Secondary	Length of the Right and Left Renal Arteries Assessed by Computed Tomographic Angiography (CTA) - Blinded Reader	The length of the left and right renal arteries were measured from the origin at the aorta to the bifurcation into the upper and lower pole arteries or the most distal point of the renal artery which could be visualized. This distal margin was the point where the diameter was still assessable. If there were more than 2 distal branches then the first large branch that was the dominant supply to a renal pole was used as the distal point.	Images were taken pre-injection and post-injection	No
Secondary	Vessel Diameter (Millimeter [mm]) at the Normal Point and the Narrowest Point in Gadobutrol-Enhanced MRA, Unenhanced MRA and CTA Images	The segment reduction in diameter (DIA) of greater than 10% was considered abnormal and measured. The diameter of each of these abnormal segments was measured using electronic calipers (perpendicular to the long axis of the vessel) at the point of most severe stenosis within each segment. Mean of vessel diameters was calculated by segment separately for CTA and MRA readers. For the ease of expression, the following abbreviations will be used: Diameter (DIA), Blinded Reader (BR).	Images were taken pre-injection and post-injection	No
Secondary	The Percentage of Location of Stenosis >= 50% (Within and Beyond 5 Millimeter From the Aorta) in the Proximal Segments Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA	Location within the right and left proximal segment was based on the point of greatest stenosis and was recorded for stenosis >=50% as: - Within 5 mm of the aorta (or occlusion proximal to the origin of the segment); - Beyond 5 mm from the aorta.	Images were taken pre-injection and post-injection	No
Secondary	The Percentage of Segments With Artifacts Presence	Artifacts were collected for the MRA images on a segmental basis.	Images were taken pre-injection and post-injection	No
Secondary	Types of Artifacts Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA by Blinded Reader 1	The following types of artifacts were considered: Motion artifact (including pulsatility, breathing, swallowing), venous opacification, saturation artifact (for example [eg], in-plane flow, turbulence, dephasing, saturation band), susceptibility artifacts (including devices, eg, stents), ringing artifact (eg, bands), bolus timing error, and other (artifact not specified above or no artifact).	Images were taken pre-injection and post-injection	No
Secondary	Types of Artifacts Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA by Blinded Reader 2	The following types of artifacts were considered: Motion artifact (including pulsatility, breathing, swallowing), venous opacification, saturation artifact (for example [eg], in-plane flow, turbulence, dephasing, saturation band), susceptibility artifacts (including devices, eg, stents), ringing artifact (eg, bands), bolus timing error, and other (artifact not specified above or no artifact).	Images were taken pre-injection and post-injection	No
Secondary	Types of Artifacts Assessed by Gadobutrol-enhanced MRA and Unenhanced MRA by Blinded Reader 3	The following types of artifacts were considered: Motion artifact (including pulsatility, breathing, swallowing), venous opacification, saturation artifact (for example [eg], in-plane flow, turbulence, dephasing, saturation band), susceptibility artifacts (including devices, eg, stents), ringing artifact (eg, bands), bolus timing error, and other (artifact not specified above or no artifact).	Images were taken pre-injection and post-injection	No
Secondary	The Percentage of Accessory (Non-dominant) Renal Artery Presence Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA	An accessory renal artery was defined as an additional, non-dominant, renal artery typically emanating from the aorta and anastomosing distal to the proximal third, segment of that renal artery. It was recorded only as present or absent on the right and left, regardless of how many accessory renal arteries were present.	Images were taken pre-injection and post-injection	No
Secondary	The Presence of Any Aneurysmal Dilatation in Each Segment (Proximal, Mid- and Distal) in the Right and the Left Renal Arteries Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA	Any focal dilatation (aneurysmal dilatation) of a segment was recorded. The diameter at the widest point was measured with the electronic calipers if a dilatation was present in any segment. The number of participants with an aneurysmal dilatation in each segment (proximal, mid- and distal) in the right and the left renal arteries assessed by gadobutrol-enhanced MRA and unenhanced MRA were reported.	Images were taken pre-injection and post-injection	No
Secondary	The Percentage of Participants With Diagnosis of Fibromuscular Dysplasia and Arteriosclerosis Assessed by Gadobutrol-Enhanced MRA and Unenhanced MRA	Any focal dilatation (aneurysmal dilatation) of a segment was recorded. The diameter at the widest point was measured with the electronic calipers if a dilatation was present in any segment. The number of participants with an aneurysmal dilatation in each segment (proximal, mid- and distal) in the right and the left renal arteries assessed by gadobutrol-enhanced MRA and unenhanced MRA were reported.	Images were taken pre-injection and post-injection	No
Secondary	Diagnostic Confidence by the Blinded Readers Using Gadobutrol-Enhanced MRA and Unenhanced MRA	Diagnostic confidence was evaluated to determine the level of certainty that the blinded readers assigned to a diagnosis for each segment. This was defined as the degree of confidence that the information on the MRA images represented the true and complete clinical picture of a particular segment. The degree of confidence was rated on a 4-point scale: 1=Not confident; 2=Somewhat confident; 3=Confident; 4=Very confident.	Images were taken pre-injection and post-injection	No
Secondary	The Percentage of Participants With Additional Imaging Studies Recommended by the Blinded Readers and the Clinical Investigator After Evaluation of the Gadobutrol-Enhanced and Unenhanced MRA Images	A measure of diagnostic value was the reduction in the number of additional diagnostic imaging studies recommended/ordered. The clinical investigators and the blinded readers were asked if they had recommended an additional imaging study for each participant, and the data were recorded.	Images were taken pre-injection and post-injection	No
Secondary	Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Gadobutrol-Enhanced and Unenhanced MRA Images - Blinded Reader 1	An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.	Images were taken pre-injection and post-injection	No
Secondary	Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Gadobutrol-Enhanced and Unenhanced MRA Images - Blinded Reader 2	An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.	Images were taken pre-injection and post-injection	No
Secondary	Types of Additional Imaging Studies Recommended by the Blinded Readers After Evaluation of the Gadobutrol-Enhanced and Unenhanced MRA Images - Blinded Reader 3	An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.	Images were taken pre-injection and post-injection	No
Secondary	Types of Additional Imaging Studies Recommended by the Clinical Investigator After Evaluation of the Unenhanced and Gadobutrol-Enhanced MRA Images	An additional imaging study recommended was specified from the following list: Non-contrast MRA, Contrast-enhanced MRA, CTA, Ultrasound, Digital subtraction catheter angiogram (DSCA), and Nuclear medicine study.	Images were taken pre-injection and post-injection	No

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