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Renal Artery ObstructionPhase 3GRAMSNCT01344460

Gadobutrol Enhanced MRA of the Renal Arteries

A Phase 3 study testing Gadobutrol (Gadovist, BAY86-4875) in people with Renal Artery Obstruction, run by Bayer at 70 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Artery Obstruction
What is being tested?
Gadobutrol (Gadovist, BAY86-4875)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
317 participants
Where
70 sitesin 13 countries
Study dates
May 2011to Jul 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

70 sites in 13 countries.

70 sites in 13 countries

United States15 sites

  • Study site

    Baltimore, Maryland, 21287

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Jacksonville, Florida, 32209

  • Study site

    Los Angeles, California, 90033

  • Study site

    Los Angeles, California, 90095

  • Study site

    Madison, Wisconsin, 53705

  • Study site

    Memphis, Tennessee, 38104

  • Study site

    Miami, Florida, 33136

  • Study site

    Milwaukee, Wisconsin, 53215

  • Study site

    Orange, California, 92660

  • Study site

    Providence, Rhode Island, 02903-4900

  • Study site

    San Antonio, Texas, 78229-3900

  • Study site

    Savannah, Georgia, 31406

  • Study site

    Tucson, Arizona, 85711

Other trials in United States

Germany7 sites

  • Study site

    Berlin, State of Berlin, 12351

  • Study site

    Frankfurt am Main, Hesse, 60596

  • Study site

    Jena, Thuringia, 07740

  • Study site

    Karlsruhe, Baden-Wurttemberg, 76133

  • Study site

    Kiel, Schleswig-Holstein, 24105

  • Study site

    Lübeck, Schleswig-Holstein, 23538

  • Study site

    Münster, North Rhine-Westphalia, 48145

Other trials in Germany

Brazil6 sites

  • Study site

    Porto Alegre, Rio Grande do Sul, 90035-001

  • Study site

    Rio de Janeiro, Rio de Janeiro, 22281-100

  • Study site

    São Paulo, São Paulo, 04023-061

  • Study site

    São Paulo, São Paulo, 05403-000

  • Study site

    São Paulo, São Paulo, 05403-900

  • Study site

    São Paulo, São Paulo, 05651-901

Other trials in Brazil

France6 sites

  • Study site

    La Tronche, 38700

  • Study site

    Paris, 75651

  • Study site

    Paris, 75877

  • Study site

    Paris, 75908

  • Study site

    Rouen, 76031

  • Study site

    Vandœuvre-lès-Nancy, 54500

Other trials in France

Czechia5 sites

  • Study site

    Brno, 625 00

  • Study site

    Olomouc, 775 20

  • Study site

    Pilsen, 304 60

  • Study site

    Prague, 12808

  • Study site

    Prague, 150 30

Other trials in Czechia

South Korea5 sites

  • Study site

    Seoul, Seoul Teugbyeolsi, 110-744

  • Study site

    Seoul, Seoul Teugbyeolsi, 135-720

  • Study site

    Seoul, 135-710

  • Study site

    Seoul

  • Study site

    Suwon, 443-721

Other trials in South Korea

Taiwan5 sites

  • Study site

    Kaoshiung, 81346

  • Study site

    Taipei, Taipei, 116

  • Study site

    Taipei, 11217

  • Study site

    Taipei

  • Study site

    Taoyuan, 333

Other trials in Taiwan

Colombia4 sites

  • Study site

    Barranquilla, Atlántico

  • Study site

    Bogotá

  • Study site

    Cali, Valle del Cauca Department

  • Study site

    Medellín, Antioquia

Other trials in Colombia

Poland4 sites

  • Study site

    Krakow, 31-02

  • Study site

    Lodz, 90-153

  • Study site

    Lublin, 20-090

  • Study site

    Warsaw, 02-097

Other trials in Poland

Switzerland4 sites

  • Study site

    Basel, Canton of Basel-City, 4031

  • Study site

    Bern, Canton of Bern, CH-3010

  • Study site

    Olten, Canton of Solothurn, 4600

  • Study site

    Zurich, Canton of Zurich, 8091

Other trials in Switzerland

Argentina3 sites

  • Study site

    Adrogué, Buenos Aires, B1846DWA

  • Study site

    Buenos Aires, Ciudad Auton. de Buenos Aires, C1425BEE

  • Study site

    Rosario, Santa Fe Province, S2000DTC

Other trials in Argentina

Austria3 sites

  • Study site

    Innsbruck, Tyrol, 6020

  • Study site

    Vienna, 1090

  • Study site

    Wiener Neustadt, 2700

Other trials in Austria

Turkey (Türkiye)3 sites

  • Study site

    Ankara, 06500

  • Study site

    Istanbul, 34098

  • Study site

    Istanbul

Other trials in Turkey (Türkiye)

About this study

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

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).

Being tested
Gadobutrol (Gadovist, BAY86-4875)
Keywords
magnetic resonance angiography (MRA) of the renal arteries
Medical subject headings
Renal Artery Obstruction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gadobutrol (Gadovist, BAY86-4875)Drug

    a single bolus injection of approx. 0.1mmol/kg

Study groups in NCT01344460
Study groupRoleWhat they receive
Arm 1ExperimentalNot described
Receives: Drug: Gadobutrol (Gadovist, BAY86-4875)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Images were taken pre-injection and post-injection

  2. 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.

    Measured: Images were taken pre-injection and post-injection

  3. 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.

    Measured: Images were taken pre-injection and post-injection

  4. 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.

    Measured: Images were taken pre-injection and post-injection

  5. 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.

    Measured: Images were taken pre-injection and post-injection

Secondary outcomes (17)

  1. 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.

    Measured: Images were taken pre-injection and post-injection

  2. 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.

    Measured: Images were taken pre-injection and post-injection

  3. 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).

    Measured: Images were taken pre-injection and post-injection

  4. 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.

    Measured: Images were taken pre-injection and post-injection

  5. The Percentage of Segments With Artifacts Presence

    Artifacts were collected for the MRA images on a segmental basis.

    Measured: Images were taken pre-injection and post-injection

  6. 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).

    Measured: Images were taken pre-injection and post-injection

  7. 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).

    Measured: Images were taken pre-injection and post-injection

  8. 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).

    Measured: Images were taken pre-injection and post-injection

  9. 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.

    Measured: Images were taken pre-injection and post-injection

  10. 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.

    Measured: Images were taken pre-injection and post-injection

  11. 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.

    Measured: Images were taken pre-injection and post-injection

  12. 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.

    Measured: Images were taken pre-injection and post-injection

  13. 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.

    Measured: Images were taken pre-injection and post-injection

  14. 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.

    Measured: Images were taken pre-injection and post-injection

  15. 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.

    Measured: Images were taken pre-injection and post-injection

  16. 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.

    Measured: Images were taken pre-injection and post-injection

  17. 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.

    Measured: Images were taken pre-injection and post-injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionJul 2012
  4. Study completionJul 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
317 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01344460
Sponsor's protocol ID
91759
Other IDs
2010-023002-13
Acronym
GRAMS
Status last verified
Jul 2015
First submitted
5 Apr 2011
Last updated
26 Aug 2015
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gadobutrol (Gadovist, BAY86-4875) in people with Renal Artery Obstruction, run by Bayer at 70 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in United States, Germany, Brazil, France, Czechia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Assessable Vascular Segments Using Gadobutrol-Enhanced MRA and Unenhanced MRA (time frame: Images were taken pre-injection and post-injection). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01344460.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2015.

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