Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparison of Cardiac Imaging Techniques for Diagnosing Coronary Artery Disease (PACIFIC)

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01521468
Recruitment Status : Completed
First Posted : January 30, 2012
Last Update Posted : December 10, 2014
Sponsor:
Information provided by (Responsible Party):
Paul Knaapen, VU University Medical Center

Tracking Information
First Submitted Date January 25, 2012
First Posted Date January 30, 2012
Last Update Posted Date December 10, 2014
Study Start Date January 2012
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 7, 2012)
  • Head to head comparison between hybrid SPECT/CTCA and PET/CTCA [ Time Frame: Invasive coronary angiography + fractional flow reserve measurements within 1 week of the initial scans ]
    A head-to-head comparison will be performed to assess the diagnostic accuracy of stress hybrid PET/CTCA and hybrid SPECT/CTCA for the detection of obstructive coronary artery disease as defined by invasive coronary angiography in combination with fractional flow reserve measurements.
  • Non-invasive imaging for risk stratification [ Time Frame: Ten years ]
    To determine the prognostic value of CTCA, SPECT, quantitative PET, hybrid SPECT/CTCA and PET/CTCA for predicting cardiac death and nonfatal myocardial infarction.
  • Improving prognostication [ Time Frame: Ten years ]
    To compare the ability and incremental value of non-invasive stand-alone and cardiac hybrid imaging over clinical, historical and exercise test data for the prediction of all cause mortality.
  • Diagnostic accuracy of CTCA, SPECT and PET [ Time Frame: Invasive coronary angiography + fractional flow reserve measurements within 1 week of the initial scans ]
    Determining the diagnostic accuracy of stand-alone cardiac imaging modalities
Original Primary Outcome Measures
 (submitted: January 27, 2012)
  • Diagnostic accuracy of non-invasive cardiac imaging [ Time Frame: Within 2 weeks after invasive coronary angiography ]
    To compare the diagnostic accuracy of CTCA, quantitative PET, SPECT, hybrid PET/CTCA, and SPECT/CTCA for the detection of obstructive epicardial coronary stenosis as defined by invasive coronary angiography (ICA) in combination with fractional flow reserve (FFR) measurements.
  • Head to head comparison between hybrid SPECT/CTCA and PET/CTCA [ Time Frame: Within 2 weeks after invasive coronary angiography ]
    A head-to-head comparison will be performed to assess the diagnostic accuracy of stress hybrid PET/CTCA and hybrid SPECT/CTCA for the detection of obstructive coronary artery disease as defined by invasive coronary angiography in combination with fractional flow reserve measurements.
  • Non-invasive imaging for risk stratification [ Time Frame: Ten years ]
    To determine the prognostic value of CTCA, SPECT, quantitative PET, hybrid SPECT/CTCA and PET/CTCA for predicting cardiac death and nonfatal myocardial infarction.
  • Post-test resource utilization [ Time Frame: 90 days ]
    To assess the impact of CTCA, PET, SPECT, PET/CTCA, and SPECT/CTCA on post-test resource utilization as measured by referral to early catheterization within 90 days and downstream use of diagnostic tests after the index study.
  • Improving prognostication [ Time Frame: Ten years ]
    To compare the ability and incremental value of non-invasive stand-alone and cardiac hybrid imaging over clinical, historical and exercise test data for the prediction of all cause mortality.
Change History Complete list of historical versions of study NCT01521468 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 27, 2012)
  • Risk stratification [ Time Frame: Ten years ]
    To determine the incremental prognostic value of several biomarkers over non-invasive imaging, clinical, historical and exercise test data to predict overall mortality, nonfatal myocardial infarction, revascularization and hospitalization for chest pain or heart failure.
  • Risk stratification [ Time Frame: > 6 months ]
    To compare the predictive and incremental value of stand-alone and cardiac hybrid imaging imaging over clinical, historical and exercise test data for the prediction of a composite endpoint including cardiac death, nonfatal myocardial infarction, late referral to revascularization, or late hospitalization for chest pain or heart failure.
  • Risk stratification [ Time Frame: > 6 months ]
    To compare the predictive and incremental value of several biomarkers over non-invasive imaging, clinical, historical and exercise test data for the prediction of a composite endpoint including cardiac death, nonfatal myocardial infarction, late referral to revascularization, or late hospitalization for chest pain or heart failure.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Comparison of Cardiac Imaging Techniques for Diagnosing Coronary Artery Disease
Official Title Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography
Brief Summary A large number of cardiac catheterizations are performed each year, primarily to diagnose heart disease. However, a cardiac catheterization is an invasive procedure which is associated with serious complications such as heart infarction, stroke, and death. Therefore, there is a need for non-invasive procedures to diagnose coronary heart disease. The purpose of this study is, therefore, to assess the diagnostic accuracy of non-invasive cardiac imaging modalities for the detection of heart disease in patients presenting for the first time to the cardiologist with chest pain.
Detailed Description

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality in Western civilized countries. Early detection of CAD allows optimal therapeutic management in order to decrease morbidity and mortality. In the Netherlands 80,000 invasive coronary angiographies are performed each year. Invasive coronary angiography (ICA), particularly in conjunction with fractional flow reserve (FFR) measurements, is considered the gold standard in diagnosing and evaluating the severity of CAD in the current era. FFR measurements during ICA are useful in determining whether a coronary stenosis is functionally important. An FFR < 0.80 is considered abnormal, reflecting a hemodynamic significant coronary stenosis. ICA has superior spatial and temporal resolution compared with non-invasive imaging techniques. However, ICA is an invasive procedure which is associated with a low, though significant, complication rate including bleeding, coronary artery dissections, cerebral embolism, cardiac arrhythmias, myocardial infarction and death. Moreover, ICA provides only limited information on the presence of atherosclerotic plaques not associated with luminal stenosis. Furthermore, conventional catheter angiography without the advent of FFR measurements, is not able to provide information about the hemodynamic significance of a significant luminal stenosis (≥ 70%), i.e. whether a coronary artery stenosis is leading to myocardial perfusion abnormalities. Therefore, there is a need for non-invasive imaging techniques for diagnosing and evaluating the hemodynamic significance of CAD. Non-invasive techniques can serve as a gatekeeper for invasive coronary angiographies in order to decrease the number of purely diagnostic invasive angiographies and associated morbidity and mortality. The detection and management of cardiovascular disease increasingly utilize non-invasive cardiac imaging in patients with suspected or known CAD. By more accurately identifying patients who are eligible for coronary revascularization with the use of non-invasive cardiac imaging, the number of unnecessary invasive diagnostic coronary angiographies can be decreased.

Study design

Positron emission tomography:

PET images will be acquired using a Gemini Time-of-Flight (TF) 64 scanner (Philips Healthcare, Best, The Netherlands). Quantitative myocardial perfusion at rest and during hyperemia in ml -1. min -1. g -1 of myocardial tissue will be measured using oxygen-15-labelled water (H215O). Pharmacological stress is induced by infusion of adenosine intravenously at a rate of 140 µg/kg/min. Two minutes after the start of adenosine vasodilation reaches a steady state and H215O will be given intravenously as a bolus followed with the start of a 6-minutes emission scan. Directly after the PET sequence, a low dose CT attenuation scan (CTAC) is acquired after which the infusion of adenosine is terminated. Technetium-99m sestamibi is injected intravenously after the second CTAC scan. A stress SPECT-scan is performed 45 minutes after the stress PET scan.

Single photon emission computed tomography:

SPECT imaging will be performed according to standard clinical protocols for myocardial perfusion imaging. All patients will undergo SPECT-imaging(Symbia T2, Siemens, The Hague, The Netherlands) on a during hyperaemia induced by infusion of adenosine at a rate of 140mcg/kg/min, using a dose of 400 megabecquerel (MBq) of Technetium (99mTc) tetrofosmin. Tetrofosmin will be administered during adenosine induced stress during the time of the PET stress perfusion scan. Directly after the stress SPECT-sequence, a low dose CT-attenuation scan (CTAC) will be performed. A SPECT- rest imaging scan will be performed 72 hours after the stress SPECT scan on the day of the catheterization.

Computed tomography:

Patients will undergo a coronary calcium score (CTCAC) and CT coronary angiography scan on a 256-slice CT scanner (Philips Brilliance iCT, Philips Healthcare, Best, the Netherlands). Prospective ECG-gating (Step & Shoot Cardiac, Philips Healthcare, Best, The Netherlands) at 75 % of the R-R interval will be performed in order to minimize radiation burden.

Invasive coronary angiography:

ICA will be performed via a transfemoral of transradial approach according to the standard procedure. Iodized contrast will be given intracoronary during the procedure to evaluate the coronary artery lumen. The operator and an interventional cardiologist blinded to the findings obtained with non-invasive imaging will evaluate the ICA images. ICA imaging will be performed with a biplane or monoplane cardiovascular X-ray system (Allura Xper FD 10/10, Philips Healthcare, Best, The Netherlands) in at least two orthogonal directions. After primary coronary angiography, FFR will be measured in all coronary arteries, using a 0.014-inch sensor tipped guide wire. A stenosis with a FFR < 0.80 will be considered as a hemodynamic significant stenosis. Clinical decision making will be based on the findings obtained with ICA and FFR measurements and will be made by the interventional cardiologist.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Urine and whole blood.
Sampling Method Non-Probability Sample
Study Population Outpatient clinic of the VU University Medical Center hospital in Amsterdam.
Condition Coronary Artery Disease
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: January 27, 2012)
210
Original Estimated Enrollment Same as current
Actual Study Completion Date December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • First presentation to cardiologist with suspected coronary artery disease
  • No documented prior history of coronary artery disease
  • Intermediate pre-test likelihood for coronary artery disease as defined by Diamond and Forrester criteria
  • Clinically referred for invasive coronary angiography
  • Age above 40 years

Exclusion Criteria:

  • History of severe chronic obstructive pulmonary disease (COPD) or chronic asthma
  • Pregnancy
  • Renal failure ( i.e. estimated glomerular filtration rate < 45 mL/min)
  • Use of sildenafil (Viagra) or dipyridamole (Persantin) that can not be terminated.
  • Contra-indications for β-blockers
  • Allergic reaction to iodized contrast
  • Concurrent or prior (within last 30 days) participation in other research studies using investigational drugs
  • Claustrophobia
  • Significant co-morbidities
  • Atrial fibrillation, second or third degree atrioventricular block
  • Tachycardia
  • Acute myocardial infarction
  • Heart failure
  • Left ventricle ejection fraction estimated < 50%
  • Cardiomyopathies
  • Previous radiation exposure in the diagnostic work-up
  • Subjects intended for short-term medical treatment or an invasive coronary intervention
  • No informed consent
Sex/Gender
Sexes Eligible for Study: All
Ages 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT01521468
Other Study ID Numbers NL33941.029.10
2011/209 ( Other Identifier: Medical Ethical Committee VU University Medical Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Paul Knaapen, VU University Medical Center
Study Sponsor VU University Medical Center
Collaborators Not Provided
Investigators
Principal Investigator: Paul Knaapen, MD, PhD VU University Medical Center, ICaR-VU
PRS Account VU University Medical Center
Verification Date December 2014