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Coronary Artery DiseasePACIFICNCT01521468

Comparison of Cardiac Imaging Techniques for Diagnosing Coronary Artery Disease

An observational study of Coronary Artery Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

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

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. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Coronary Artery Disease
How many people
210 participants
Where
1 siteNetherlands
Study dates
Jan 2012to Dec 2014
Phase
Observational
Are there results?
None posted in the registry

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

Study population: Outpatient clinic of the VU University Medical Center hospital in Amsterdam.

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • VU University Medical Center

    Amsterdam, 1081 HV

Other trials in Netherlands

About this study

Official title: Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography

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.

Read the 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.

Keywords
Coronary artery disease, Diagnostic accuracy, CT coronary angiography, Positron emission tomography, Single photon emission tomography, Noninvasive techniques, Cardiac catheterization, Fractional flow reserve
Medical subject headings
Coronary Artery Disease

What is being measured

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

  1. Head to head comparison between hybrid SPECT/CTCA and PET/CTCA

    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.

    Measured: Invasive coronary angiography + fractional flow reserve measurements within 1 week of the initial scans

  2. Non-invasive imaging for risk stratification

    To determine the prognostic value of CTCA, SPECT, quantitative PET, hybrid SPECT/CTCA and PET/CTCA for predicting cardiac death and nonfatal myocardial infarction.

    Measured: Ten years

  3. Improving prognostication

    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.

    Measured: Ten years

  4. Diagnostic accuracy of CTCA, SPECT and PET

    Determining the diagnostic accuracy of stand-alone cardiac imaging modalities

    Measured: Invasive coronary angiography + fractional flow reserve measurements within 1 week of the initial scans

Secondary outcomes (3)

  1. Risk stratification

    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.

    Measured: Ten years

  2. Risk stratification

    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.

    Measured: > 6 months

  3. Risk stratification

    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.

    Measured: > 6 months

Timeline

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

  1. First posted30 Jan 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01521468
Sponsor's protocol ID
NL33941.029.10
Other IDs
2011/209
Acronym
PACIFIC
Status last verified
Dec 2014
First submitted
25 Jan 2012
Last updated
10 Dec 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Kajander S, Joutsiniemi E, Saraste M, Pietila M, Ukkonen H, Saraste A, Sipila HT, Teras M, Maki M, Airaksinen J, Hartiala J, Knuuti J. Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease. Circulation. 2010 Aug 10;122(6):603-13. doi: 10.1161/CIRCULATIONAHA.109.915009. Epub 2010 Jul 26.

    PubMed 20660808

  • Di Carli MF, Hachamovitch R. New technology for noninvasive evaluation of coronary artery disease. Circulation. 2007 Mar 20;115(11):1464-80. doi: 10.1161/CIRCULATIONAHA.106.629808. No abstract available.

    PubMed 17372188

  • Gaemperli O, Husmann L, Schepis T, Koepfli P, Valenta I, Jenni W, Alkadhi H, Luscher TF, Kaufmann PA. Coronary CT angiography and myocardial perfusion imaging to detect flow-limiting stenoses: a potential gatekeeper for coronary revascularization? Eur Heart J. 2009 Dec;30(23):2921-9. doi: 10.1093/eurheartj/ehp304. Epub 2009 Aug 14.

    PubMed 19684023

  • Schuijf JD, Wijns W, Jukema JW, Atsma DE, de Roos A, Lamb HJ, Stokkel MP, Dibbets-Schneider P, Decramer I, De Bondt P, van der Wall EE, Vanhoenacker PK, Bax JJ. Relationship between noninvasive coronary angiography with multi-slice computed tomography and myocardial perfusion imaging. J Am Coll Cardiol. 2006 Dec 19;48(12):2508-14. doi: 10.1016/j.jacc.2006.05.080. Epub 2006 Nov 28.

    PubMed 17174190

  • Knaapen P, de Haan S, Hoekstra OS, Halbmeijer R, Appelman YE, Groothuis JG, Comans EF, Meijerink MR, Lammertsma AA, Lubberink M, Gotte MJ, van Rossum AC. Cardiac PET-CT: advanced hybrid imaging for the detection of coronary artery disease. Neth Heart J. 2010 Feb;18(2):90-8. doi: 10.1007/BF03091744.

    PubMed 20200615

  • Pijls NH, De Bruyne B, Peels K, Van Der Voort PH, Bonnier HJ, Bartunek J Koolen JJ, Koolen JJ. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996 Jun 27;334(26):1703-8. doi: 10.1056/NEJM199606273342604.

    PubMed 8637515

  • Levin DC. Invasive evaluation (coronary arteriography) of the coronary artery disease patient: clinical, economic and social issues. Circulation. 1982 Nov;66(5 Pt 2):III71-9.

    PubMed 7127709

  • Pazhenkottil AP, Nkoulou RN, Ghadri JR, Herzog BA, Kuest SM, Husmann L, Wolfrum M, Goetti R, Buechel RR, Gaemperli O, Luscher TF, Kaufmann PA. Impact of cardiac hybrid single-photon emission computed tomography/computed tomography imaging on choice of treatment strategy in coronary artery disease. Eur Heart J. 2011 Nov;32(22):2824-9. doi: 10.1093/eurheartj/ehr232. Epub 2011 Jul 30.

    PubMed 21804107

  • Gaemperli O, Bengel FM, Kaufmann PA. Cardiac hybrid imaging. Eur Heart J. 2011 Sep;32(17):2100-8. doi: 10.1093/eurheartj/ehr057. Epub 2011 Mar 15.

    PubMed 21406437

  • Pazhenkottil AP, Nkoulou RN, Ghadri JR, Herzog BA, Buechel RR, Kuest SM, Wolfrum M, Fiechter M, Husmann L, Gaemperli O, Kaufmann PA. Prognostic value of cardiac hybrid imaging integrating single-photon emission computed tomography with coronary computed tomography angiography. Eur Heart J. 2011 Jun;32(12):1465-71. doi: 10.1093/eurheartj/ehr047. Epub 2011 Feb 14.

    PubMed 21320906

  • Ding Y, Hoek R, Kamila PA, Danad I, Nurmohamed NS, Jukema RA, Raijmakers PG, Driessen RS, van Diemen PA, Choi AD, Knuuti J, Knaapen P, Liu H, Bax JJ, van Rosendael A; on the behalf of the PACIFIC-1 Investigators.. PET-based assessment of coronary microvascular dysfunction and its relation to plaque burden and vascular remodeling: integration with microvascular resistance reserve. Eur J Nucl Med Mol Imaging. 2026 Jul 6. doi: 10.1007/s00259-026-08054-3. Online ahead of print.

    PubMed 42406072

  • Rasmussen LD, Hoek R, Westra J, Soby JH, Maaniitty T, Braathen AT, Saraste A, Isaksen C, Nissen L, Petersen SE, Aakhus S, Knaapen P, Gormsen LC, Christiansen EH, Knuuti JM, Bottcher M, Driessen RS, Winther S. Diagnostic yield of second-line functional imaging after an abnormal coronary computed tomography angiography: an individual patient-data meta-analysis. Eur Heart J Cardiovasc Imaging. 2026 Jun 1;27(6):1176-1189. doi: 10.1093/ehjci/jeag088.

    PubMed 41913985

  • Wilgenhof A, Jukema RA, Driessen RS, Danad I, Raijmakers PG, van Royen N, van Nunen LX, Collet C, de Waard GA, Knaapen P. The effect of hydrostatic pressure on invasive coronary pressure measurements: Comparison with [15O]H2O-positron emission tomography flow data. Catheter Cardiovasc Interv. 2024 Nov;104(5):980-989. doi: 10.1002/ccd.31215. Epub 2024 Sep 11.

    PubMed 39258435

  • Arai AE. Why Should We Quantify Stress Myocardial Perfusion CMR? JACC Cardiovasc Imaging. 2024 Mar;17(3):266-268. doi: 10.1016/j.jcmg.2023.08.015. Epub 2023 Oct 18. No abstract available.

    PubMed 37855801

  • Lin A, van Diemen PA, Motwani M, McElhinney P, Otaki Y, Han D, Kwan A, Tzolos E, Klein E, Kuronuma K, Grodecki K, Shou B, Rios R, Manral N, Cadet S, Danad I, Driessen RS, Berman DS, Norgaard BL, Slomka PJ, Knaapen P, Dey D. Machine Learning From Quantitative Coronary Computed Tomography Angiography Predicts Fractional Flow Reserve-Defined Ischemia and Impaired Myocardial Blood Flow. Circ Cardiovasc Imaging. 2022 Oct;15(10):e014369. doi: 10.1161/CIRCIMAGING.122.014369. Epub 2022 Oct 13.

    PubMed 36252116

Questions about this trial

What is this clinical trial studying?

An observational study of Coronary Artery Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

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 5 inclusion and 18 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 10 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

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). The study lists 4 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 NCT01521468, which also lists 16 linked publications.

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 10 Dec 2014.

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