Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01890434




Registration number
NCT01890434
Ethics application status
Date submitted
27/06/2013
Date registered
1/07/2013
Date last updated
31/07/2019

Titles & IDs
Public title
Gadobutrol / Gadavist-enhanced Cardiac Magnetic Resonance Imaging (CMRI) to Detect Coronary Artery Disease (CAD)
Scientific title
Multicenter Open-label Study to Evaluate Efficacy of Gadobutrol-enhanced Cardiac Magnetic Resonance Imaging (CMRI) for Detection of Significant Coronary Artery Disease (CAD) in Subjects With Known or Suspected CAD by a Blinded Image Analysis
Secondary ID [1] 0 0
2013-000066-11
Secondary ID [2] 0 0
15962
Universal Trial Number (UTN)
Trial acronym
GadaCAD 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gadobutrol (Gadavist, Gadovist, BAY86-4875)

Experimental: Gadobutrol 0.1 mmol/kg body weight - 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.


Treatment: Drugs: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Sensitivity Based on Blinded Readers' Assessment
Timepoint [1] 0 0
0 to 30/40 min post-injection
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
0 to 30/40 min post-injection
Primary outcome [3] 0 0
Absence of Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Primary Analysis of Specificity Based on Blinded Readers' Assessment
Timepoint [3] 0 0
0 to 30/40 min post-injection
Primary outcome [4] 0 0
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
Timepoint [4] 0 0
0 to 30/40 min post-injection
Primary outcome [5] 0 0
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
Timepoint [5] 0 0
0 to 30/40 min post-injection
Primary outcome [6] 0 0
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
Timepoint [6] 0 0
0 to 30/40 min post-injection
Secondary outcome [1] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Investigator's Assessment
Timepoint [1] 0 0
0 to 30/40 min post-injection
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
0 to 30/40 min post-injection
Secondary outcome [3] 0 0
Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI - Secondary Analysis of Specificity Based on Investigator's Assessment
Timepoint [3] 0 0
0 to 30/40 min post-injection
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
0 to 30/40 min post-injection
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
0 to 30/40 min post-injection
Secondary outcome [6] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI and Unenhanced Wall Motion CMRI Images - Additional Secondary Analysis of Sensitivity Comparison Based on the Investigator's Assessment
Timepoint [6] 0 0
0 to 30/40 min post-injection
Secondary outcome [7] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus GSPECT - Secondary Analysis of Sensitivity Comparison Based on Majority Blinded Reader's and Investigator's Assessment
Timepoint [7] 0 0
0 to 30/40 min post-injection
Secondary outcome [8] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD Per Participant on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Sensitivity Based on Majority Blinded Reader's and Investigator's Assessment
Timepoint [8] 0 0
0 to 30/40 min post-injection
Secondary outcome [9] 0 0
Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI Versus GSPECT -- Secondary Analysis of Specificity Comparison Based on Majority Blinded Reader's and Investigator's Assessment
Timepoint [9] 0 0
0 to 30/40 min post-injection
Secondary outcome [10] 0 0
Absence of a Myocardial Perfusion Defect Excluding Significant CAD Per Participant on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Specificity Based on Majority Blinded Reader's and Investigator's Assessment
Timepoint [10] 0 0
0 to 30/40 min post-injection
Secondary outcome [11] 0 0
Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment
Timepoint [11] 0 0
0 to 30/40 min post-injection
Secondary outcome [12] 0 0
Localization of a Myocardial Perfusion Defect to LAD and Non-LAD Territory on GSPECT - Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment
Timepoint [12] 0 0
0 to 30/40 min post-injection
Secondary outcome [13] 0 0
Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment
Timepoint [13] 0 0
0 to 30/40 min post-injection
Secondary outcome [14] 0 0
Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessment
Timepoint [14] 0 0
0 to 30/40 min post-injection
Secondary outcome [15] 0 0
Localization of a Myocardial Perfusion Defect to LAD and Non-LAD Territory on GSPECT - Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessment
Timepoint [15] 0 0
0 to 30/40 min post-injection
Secondary outcome [16] 0 0
Localization of a Myocardial Perfusion Defect to Each Coronary Territory on Gadobutrol-enhanced CMRI - Additional Secondary Analysis of Specificity Based on Blinded Readers' and Investigator's Assessment
Timepoint [16] 0 0
0 to 30/40 min post-injection
Secondary outcome [17] 0 0
Detection of Myocardial Perfusion Defect(s) on Gadobutrol-enhanced CMRI in Participants With Significant LMS Stenosis - Based on Blinded Readers' and Investigator's Assessment
Timepoint [17] 0 0
0 to 30/40 min post-injection
Secondary outcome [18] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD in Participants With Single or Multi-vessel Disease Evaluated on Gadobutrol-enhanced CMRI - Secondary Analysis of Sensitivity Based on Blinded Readers' and Investigator's Assessment
Timepoint [18] 0 0
0 to 30/40 min post-injection
Secondary outcome [19] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD in Participants With Single-vessel Disease Evaluated on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Sensitivity by Majority Blinded Reader and Investigator
Timepoint [19] 0 0
0 to 30/40 min post-injection
Secondary outcome [20] 0 0
Presence of a Myocardial Perfusion Defect Indicating Significant CAD in Participants With Multi-vessel Disease Evaluated on Gadobutrol-enhanced CMRI and GSPECT - Additional Secondary Analysis of Sensitivity by Majority Blinded Reader and Investigator
Timepoint [20] 0 0
0 to 30/40 min post-injection
Secondary outcome [21] 0 0
Number of Participants by Their Lowest Confidence in Diagnosis Obtained on Gadobutrol-enhanced CMRI and Unenhanced Wall Motion CMRI - Based on Blinded Readers' and Investigator's Assessment
Timepoint [21] 0 0
0 to 30/40 min post-injection

Eligibility
Key inclusion criteria
* Male or female subjects aged =18 years
* Subjects with suspected or known CAD based on signs and/or (typical or atypical) chest pain who have routine CA without intervention within plus/minus 4 weeks of gadobutrol-enhanced CMRI or subjects at low risk of CAD with / or scheduled to get a CTA for the purpose of exclusion of CAD within plus/minus 6 weeks of gadobutrol-enhanced CMRI
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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)
* Acute myocardial infarction (< 14 days prior to inclusion), unstable angina / acute coronary syndrome, severe congestive heart failure
* 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

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/11/2016
Sample size
Target
Accrual to date
Final
478
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Perth
Recruitment hospital [3] 0 0
- Chermside
Recruitment hospital [4] 0 0
- North Adelaide
Recruitment postcode(s) [1] 0 0
5042 - Adelaide
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment postcode(s) [3] 0 0
4032 - Chermside
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT01890434
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01890434