Gadobutrol/Gadavist-enhanced Cardiac Magnetic Resonance Imaging (CMRI) to Detect Coronary Artery Disease (CAD)

NCT01890421 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 159612012-002563-10
• Study Type: interventional
• Target: 426
• Locations: 7 countries
• Sites: 23

Brief Summary

Participants being evaluated for suspected or known Coronary artery Disease (CAD) based on signs and/or symptoms, will be invited to participate in the study. The duration for a participant in the study may range from 2 days to 4-6 weeks. One to four visits to the study doctor will be required. This study will investigate the diagnostic results of gadobutrol-enhanced Cardiac Magnetic Resonance Imaging (CMRI) images regarding the detection (sensitivity) and exclusion (specificity) of coronary artery disease utilizing a uniform image acquisition software. The CMR images will be tested either against the results from routine clinical Coronary Angiography (CA) or those from Computed Tomography Angiography (CTA), which is used as the standard of reference. The CA/CTA may have been performed up to 4 weeks prior to enrollment or be scheduled up to 4/6 weeks after the study. CMRI and CA/CTA images will be collected for an independent image review (blinded read).

Conditions

Coronary Artery Disease

Keywords

Myocardial Perfusion Imaging

Outcome Measures

Primary Outcomes (6)

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI (Based on RPS) - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment

  Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)\]. A myocardial region a perfusion defect in case of a RPS of \>=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of \>=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative).

  0 to 30/40 minute (min) post-injection

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI (Based on RPS) - Additional Secondary Analysis of Sensitivity Based on the Blinded Readers' Assessment

  Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)\]. A myocardial region a perfusion defect in case of a RPS of \>=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of \>=70% for secondary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.

  0 to 30/40 min post-injection

• Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI (Based on RPS) - Primary Analysis of Specificity Based on the Blinded Readers' Assessment

  Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)\]. A myocardial region a perfusion defect in case of a RPS of \>=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of \>=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Specificity= true negative/ (true negative + false positive).

  0 to 30/40 min post-injection

• Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI (Based on RPS) - Additional Secondary Analysis of Specificity Based on the Blinded Readers' Assessment

  Blinded readers evaluated 6 myocardial regions based on regional perfusion score (RPS), 0=normal; 1=abnormal, reversible perfusion defect (stress); 2=abnormal, mixed perfusion defect (reversible and fixed/permanent components); 3=abnormal, fixed/permanent perfusion defect/scar (stress and rest)\]. A myocardial region a perfusion defect in case of a RPS of \>=1 and was rated to have normal perfusion in case of a RPS of 0. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of \>=70% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was prospective analysis.

  0 to 30/40 min post-injection

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images - Primary Analysis of Sensitivity Comparison Based on the Blinded Readers' Assessment

  Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by blinded readers' assessment. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of \>=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative).

  0 to 30/40 min post-injection

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images - Additional Secondary Analysis of Sensitivity Comparison Based on the Blinded Readers' Assessment

  Presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI versus the presence of wall motion abnormalities on unenhanced CMRI images (based on regional perfusion/regional wall motion score of the 6 myocardial regions) was calculated by blinded readers' assessment. Significant CAD was defined as quantitative coronary angiography (QCA) stenosis of \>=70% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) verified by standard of reference (SoR). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was prospective analysis.

  0 to 30/40 min post-injection

Secondary Outcomes (14)

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Investigator's Assessment

  0 to 30/40 min post-injection

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment

  0 to 30/40 min post-injection

• Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Specificity Based on Investigator's Assessment

  0 to 30/40 min post-injection

• Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Specificity Based on Investigator's Assessment

  0 to 30/40 min post-injection

• Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus Unenhanced Wall Motion CMRI Images - Secondary Analysis of Sensitivity Comparison Based on Investigator's Assessment

  0 to 30/40 min post-injection

Study Arms (1)

Gadobutrol 0.1 mmol/kg body weight

EXPERIMENTAL

Participants received gadobutrol at the total approved standard dose of 0.1 millimole per kilogram body weight (mmol/kg BW) in 2 separate bolus injections: 0.05 mmol/kg BW at peak pharmacologic stress and 0.05 mmol/kg BW at rest via a power injector.

Drug: Gadobutrol (Gadovist, Gadavist, BAY86-4875)

Interventions

Gadobutrol (Gadovist, Gadavist, BAY86-4875) DRUG

Participants received gadobutrol at the total approved standard dose of 0.1 millimole per kilogram body weight (mmol/kg BW) in 2 separate bolus injections: 0.05 mmol/kg BW at peak pharmacologic stress and 0.05 mmol/kg BW at rest via a power injector.

Gadobutrol 0.1 mmol/kg body weight

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged ≥18 years
• Participants with suspected or known CAD based on signs and/or (typical or atypical) chest pain who have routine CA without intervention or CTA within 4 weeks around gadobutrol-enhanced CMRI
• Willingness to undergo stress/rest CMRI and to follow directions and complete all study procedures
• Women of childbearing potential (e.g. age \< 60y, no history of surgical sterilization or hysterectomy): use of contraception and a negative pregnancy test

You may not qualify if:

• Suspected clinical instability or unpredictability of the clinical course during the study period
• Contraindication to the cardiac MRI examination (e.g. inability to hold breath; severe claustrophobia, metallic devices such as pace makers)
• History of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents according to the investigator's assessment / judgment
• Estimated glomerular filtration rate (eGFR) value \<30 mL/min/1.73 m\^2 derived from a serum / blood creatinine result within 2 weeks prior to gadobutrol injection. Any participant on hemodialysis or peritoneal dialysis is excluded from enrollment.
• Acute renal insufficiency
• Coronary artery bypass grafting (CABG)
• Irregular heart rhythm
• Condition that precludes the safe administration of pharmacological stressor according to the respective approved label such as sinus node disease, 2nd or 3rd degree atrioventricular block, obstructive lung disease

Sponsors & Collaborators

• Bayer: lead

Study Sites (23)

Unknown Facility

Minneapolis, Minnesota, 55455, United States

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Marseille, 13385, France

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Saint-Etienne, 42055, France

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Bad Krozingen, Baden-Wurttemberg, 79189, Germany

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Stuttgart, Baden-Wurttemberg, 70376, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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Darmstadt, Hesse, 64287, Germany

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Göttingen, Lower Saxony, 37075, Germany

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Bonn, North Rhine-Westphalia, 53115, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Leipzig, Saxony, 04289, Germany

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Berlin, 10709, Germany

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Berlin, 12203, Germany

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Berlin, 13125, Germany

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Auckland, New Zealand

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Incheon, 21565, South Korea

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Seoul, 05030, South Korea

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Seoul, 05505, South Korea

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Yangsan, 50612, South Korea

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Lugano, Canton Ticino, 6900, Switzerland

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Leicester, LE3 9QP, United Kingdom

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Liverpool, L14 3PE, United Kingdom

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London, SW3 6NP, United Kingdom

Location

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

gadobutrol

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

+1 888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2013
• First Posted: July 1, 2013
• Study Start: July 19, 2013
• Primary Completion: April 10, 2015
• Study Completion: August 31, 2017
• Last Updated: May 16, 2018
• Results First Posted: May 16, 2018

Record last verified: 2018-04

Locations

US (1); NZ (1); DE (11); KR (4); CH (1); FR (2); GB (3)