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

NCT01890434 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 159622013-000066-11
• Study Type: interventional
• Target: 478
• Locations: 4 countries
• Sites: 24

Brief Summary

Subjects 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 subject in the study may range from 2 days to 4-6 weeks. One to four visits to the study doctor will be required. The primary objective of this study is to demonstrate that sensitivity and specificity of gadobutrol-enhanced cardiac magnetic resonance imaging (CMRI) exceed pre-specified minimum performance thresholds of 60% and 55%, respectively, and to show superior sensitivity over unenhanced wall motion CMRI at vasodilator rest/stress for the detection of significant CAD. The CMR images acquired with a uniform imaging acquisition software will be evaluated either against the results from routine clinical Coronary Angiography (CA) or Computed Tomography Angiography (CTA), which are the standard of reference. 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 - 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 was rated to have 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, coronary angiography \[CA\] or computed tomography angiography \[CTA, only if disease can be unequivocally rejected\]). 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 - Additional Secondary 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 was rated to have 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 QCA stenosis of \>=70%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was retrospective analysis.

  0 to 30/40 min post-injection

• Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity 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 was rated to have 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 QCA stenosis of \>=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). 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 - Additional Secondary Analysis of Specificity 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 was rated to have 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 QCA stenosis of \>=70%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). Specificity= true negative/ (true negative + false positive). This additional secondary analysis of specificity was retrospective 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 QCA stenosis of \>=50% for primary analysis, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or the presence of wall motion abnormalities on unenhanced CMRI images verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). 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 QCA stenosis of \>=70%, and was determined based on the presence of a myocardial perfusion defect on gadobutrol-enhanced CMRI or the presence of wall motion abnormalities on unenhanced CMRI images verified by SoR (CA or CTA \[only if disease can be unequivocally rejected\]). Sensitivity= true positive/ (true positive + false negative). This additional secondary analysis of sensitivity was retrospective analysis.

  0 to 30/40 min post-injection

Secondary Outcomes (21)

• 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 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 the 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 (Gadavist, Gadovist, BAY86-4875)

Interventions

Gadobutrol (Gadavist, Gadovist, 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 subjects aged ≥18 years
• Willingness to undergo unenhanced wall motion and gadobutrol-enhanced CMRI at stress/rest and gated single photon emission computed tomography (GSPECT, if GSPECT will be a study procedure)
• Women of childbearing potential (e.g. age \< 60y, no history of surgical sterilization or hysterectomy): use of contraception and a negative pregnancy test
• Subjects who are scheduled for / have undergone routine GSPECT or undergo GSPECT as a study procedure at stress and at rest within ± 4 weeks of gadobutrol-enhanced CMRI

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 subject 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 (24)

Unknown Facility

Tucson, Arizona, 85724, United States

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Los Angeles, California, 90048-0750, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60611-2908, United States

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Bethesda, Maryland, 20814, United States

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Bethesda, Maryland, 20892, United States

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Boston, Massachusetts, 02114, United States

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St Louis, Missouri, 63110, United States

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Durham, North Carolina, 27710, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43210, United States

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Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, 29425, United States

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Houston, Texas, 77030, United States

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Charlottesville, Virginia, 22908, United States

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Adelaide, South Australia, 5042, Australia

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Perth, Western Australia, 6000, Australia

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Chermside, 4032, Australia

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North Adelaide, 5006, Australia

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London, Ontario, N6A 5A5, Canada

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Montreal, Quebec, H1T 1C8, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Singapore, 168752, Singapore

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Singapore, Singapore

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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: LTE60
• 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: August 26, 2013
• Primary Completion: August 6, 2016
• Study Completion: November 10, 2016
• Last Updated: July 31, 2019
• Results First Posted: May 16, 2018

Record last verified: 2019-07

Locations

SG (2); AU (4); CA (3); US (15)