Clinical trial NCT02184117: CONTRAST (Can cONTrast Injection Better Approximate FFR compAred to Pure reSTing Physiology?)
Official title: CONTRAST (Can cONTrast Injection Better Approximate FFR compAred to Pure reSTing Physiology?)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Keywords: Fractional Flow Reserve, Myocardial
Adenosine
Contrast Media
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Abbott Medical Devices
First posted: 2014-07-09
Enrollment: 763
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing FFR assessment for standard clinical indications

Brief summary: The purpose of this study is to determine the diagnostic performances of iodine contrast medium and resting conditions to predict fractional flow reserve (FFR). Reference FFR will be measured using standard adenosine. We hypothesize that contrast FFR will offer superior diagnostic agreement compared to resting conditions.

Detailed description: We are conducting a diagnostic accuracy study. The reference standard is adenosine-derived FFR. The diagnostic tests undergoing evaluation are resting conditions and hyperemia induced by intracoronary injection of contrast medium. While all these tests give a continuous result, we will apply binary cutoffs for comparison to FFR≤0.8 as the reference standard. Subjects will be selected prospectively from consecutive patients undergoing FFR assessment for standard clinical indications. The paired comparative design means that each patient will undergo resting (baseline), post-contrast, and adenosine-derived measurements. To enhance test integrity, all pressure recordings will be analyzed in a central physiology core laboratory blinded to clinical data and recruiting site.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older.
* Undergoing FFR assessment for standard clinical indications.
* Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria:

* Prior coronary artery bypass grafting (CABG).
* Extremely tortuous or calcified coronary arteries precluding intracoronary physiologic measurements. Operators may exclude subtotal or similar high-grade lesions, which in their judgment may be threatened by pressure wire placement.
* Known severe left ventricular hypertrophy (septal wall thickness at echocardiography of \>13 mm).
* Inability to receive adenosine (for example, severe reactive airway disease, marked hypotension, or advanced atrioventricular block without pacemaker).
* Recent (within 3 weeks prior to cardiac catheterization) ST-segment elevation myocardial infarction (STEMI) in any arterial distribution (not specifically target lesion).
* Culprit lesions (based on clinical judgment of the operator) for either STEMI or non-STEMI cannot be included.
* Severe cardiomyopathy (ejection fraction \<30%).
* Renal insufficiency such that an additional 12 to 20 mL of contrast would, in the opinion of the operator, pose unwarranted risk to the patient.

Primary outcomes:
measure: Agreement with binary FFR≤0.80
timeFrame: Baseline
Secondary outcomes:
measure: Binary diagnostic performance
timeFrame: Baseline
measure: Continuous relationship with FFR
timeFrame: Baseline
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University, Palo Alto VA
state: California
city: Oklahoma City
country: United States
facility: Integris Health
state: Oklahoma
city: Aalst
country: Belgium
facility: Cardiovascular Center (OLV-Ziekenhuis)
city: Lyon
country: France
facility: Hôpital Louis Pradel
city: Naples
country: Italy
facility: University of Naples Federico II
city: Seoul
country: Korea, Republic of
facility: Seoul National University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Noord-Brabant
city: Lisbon
country: Portugal
facility: Hospital Fernando Fonseca
city: Stockholm
country: Sweden
facility: Södersjukhuset
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
Study officials:
affiliation: University of Texas Medical School at Houston
name: Nils P Johnson, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: William F Fearon, MD
role: STUDY_DIRECTOR
References:
citation: De Bruyne B, Pijls NH, Barbato E, Bartunek J, Bech JW, Wijns W, Heyndrickx GR. Intracoronary and intravenous adenosine 5'-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation. 2003 Apr 15;107(14):1877-83. doi: 10.1161/01.CIR.0000061950.24940.88. Epub 2003 Mar 31.
citation: Johnson NP, Jeremias A, Zimmermann FM, Adjedj J, Witt N, Hennigan B, Koo BK, Maehara A, Matsumura M, Barbato E, Esposito G, Trimarco B, Rioufol G, Park SJ, Yang HM, Baptista SB, Chrysant GS, Leone AM, Berry C, De Bruyne B, Gould KL, Kirkeeide RL, Oldroyd KG, Pijls NHJ, Fearon WF. Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment. JACC Cardiovasc Interv. 2016 Apr 25;9(8):757-767. doi: 10.1016/j.jcin.2015.12.273.
citation: Johnson NP, Matsuo H, Nakayama M, Eftekhari A, Kakuta T, Tanaka N, Christiansen EH, Kirkeeide RL, Gould KL. Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses. JACC Cardiovasc Interv. 2021 Sep 13;14(17):1904-1913. doi: 10.1016/j.jcin.2021.07.041.
citation: Johnson NP, Collet C. Can FFR After Stenting Help Reduce Target Vessel Failure? JACC Cardiovasc Interv. 2021 Sep 13;14(17):1901-1903. doi: 10.1016/j.jcin.2021.08.001. No abstract available.
citation: Gould KL, Johnson NP, Roby AE, Nguyen T, Kirkeeide R, Haynie M, Lai D, Zhu H, Patel MB, Smalling R, Arain S, Balan P, Nguyen T, Estrera A, Sdringola S, Madjid M, Nascimbene A, Loyalka P, Kar B, Gregoric I, Safi H, McPherson D. Regional, Artery-Specific Thresholds of Quantitative Myocardial Perfusion by PET Associated with Reduced Myocardial Infarction and Death After Revascularization in Stable Coronary Artery Disease. J Nucl Med. 2019 Mar;60(3):410-417. doi: 10.2967/jnumed.118.211953. Epub 2018 Aug 16.
citation: Johnson NP, Kirkeeide RL, Gould KL. Same Lesion, Different Artery, Different FFR!? JACC Cardiovasc Imaging. 2019 Apr;12(4):718-721. doi: 10.1016/j.jcmg.2017.11.029. Epub 2018 Jan 17. No abstract available.
citation: Kobayashi Y, Johnson NP, Zimmermann FM, Witt N, Berry C, Jeremias A, Koo BK, Esposito G, Rioufol G, Park SJ, Nishi T, Choi DH, Oldroyd KG, Barbato E, Pijls NHJ, De Bruyne B, Fearon WF; CONTRAST Study Investigators. Agreement of the Resting Distal to Aortic Coronary Pressure With the Instantaneous Wave-Free Ratio. J Am Coll Cardiol. 2017 Oct 24;70(17):2105-2113. doi: 10.1016/j.jacc.2017.08.049.
citation: Nishi T, Johnson NP, De Bruyne B, Berry C, Gould KL, Jeremias A, Oldroyd KG, Kobayashi Y, Choi DH, Pijls NHJ, Fearon WF; CONTRAST Study Investigators. Influence of Contrast Media Dose and Osmolality on the Diagnostic Performance of Contrast Fractional Flow Reserve. Circ Cardiovasc Interv. 2017 Oct;10(10):e004985. doi: 10.1161/CIRCINTERVENTIONS.117.004985.
citation: Matsumura M, Johnson NP, Fearon WF, Mintz GS, Stone GW, Oldroyd KG, De Bruyne B, Pijls NHJ, Maehara A, Jeremias A. Accuracy of Fractional Flow Reserve Measurements in Clinical Practice: Observations From a Core Laboratory Analysis. JACC Cardiovasc Interv. 2017 Jul 24;10(14):1392-1401. doi: 10.1016/j.jcin.2017.03.031.
citation: Gargiulo G, Stabile E, Ferrone M, Barbato E, Zimmermann FM, Adjedj J, Hennigan B, Matsumura M, Johnson NP, Fearon WF, Jeremias A, Trimarco B, Esposito G; CONTRST Study Investigators. Diabetes does not impact the diagnostic performance of contrast-based fractional flow reserve: insights from the CONTRAST study. Cardiovasc Diabetol. 2017 Jan 13;16(1):7. doi: 10.1186/s12933-016-0494-2.
citation: Johnson NP, Gould KL, Di Carli MF, Taqueti VR. Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future? J Am Coll Cardiol. 2016 Jun 14;67(23):2772-2788. doi: 10.1016/j.jacc.2016.03.584.
citation: Gould KL, Johnson NP. Coronary Blood Flow After Acute MI: Alternative Truths. JACC Cardiovasc Interv. 2016 Mar 28;9(6):614-7. doi: 10.1016/j.jcin.2016.02.009. No abstract available.
citation: Gould KL, Johnson NP. Myocardial Bridges: Lessons in Clinical Coronary Pathophysiology. JACC Cardiovasc Imaging. 2015 Jun;8(6):705-9. doi: 10.1016/j.jcmg.2015.02.013. No abstract available.
citation: Gould KL, Johnson NP, Kaul S, Kirkeeide RL, Mintz GS, Rentrop KP, Sdringola S, Virmani R, Narula J. Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics. Circ Cardiovasc Imaging. 2015 May;8(5):e003099. doi: 10.1161/CIRCIMAGING.114.003099. No abstract available.