DeFACTO: Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography

• Sponsor: HeartFlow, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01233518
• Collaborator: Baim Institute for Clinical Research (Other), Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other), Minneapolis Heart Institute Foundation (Other)
• Enrollment: 285
• Location: 1
• Arm: 1
• Duration (Months): 13
• Patients Per Site Per Month: 21.9

Study Details

Study Description

Brief Summary

This is a prospective, multi-center trial conducted at up to 20 US, Canadian, European and Asian centers designed to determine the diagnostic performance of CT-FLOW (the investigational technology) by coronary computed tomographic angiography (CCTA) for non-invasive assessment of the hemodynamic significance of coronary lesions, as compared to direct measurement of fractional flow reserve (FFR) during cardiac catheterization as a reference standard.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Device: FFR	N/A

Detailed Description

285 patient, prospective, multi-center trial conducted at up to 20 US, Canadian, European and Asian centers designed to determine the diagnostic performance of CT-FLOW (the investigational technology) by coronary computed tomographic angiography (CCTA) for non-invasive assessment of the hemodynamic significance of coronary lesions, as compared to direct measurement of fractional flow reserve (FFR) during cardiac catheterization as a reference standard

Study Design

• Study Type: Interventional
• Actual Enrollment: 285 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: Single arm study Patients will receive cCTA, ICA, FFR, and cFFR per protocol.	Device: FFR; Fractional flow reserve measured during cardiac catheterization

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Diagnostic Accuracy of CCTA Plus FFRCT and CCTA Alone [1 day]

   Diagnostic accuracy of CCTA (Cardiac Computed Tomography Angiography) plus FFRCT (Noninvasive Fractional Flow Reserve computed from CCTA) to determine presence or absence of at least one hemodynamically (HD)-significant coronary artery stenosis* at the subject level using binary outcomes when compared to invasive FFR (Fractional Flow Reserve) as the reference standard. In the per-patient analysis, vessels with the most adverse clinical status were selected to represent a given patient. FFR and FFRCT measurements were recorded on a continuous scale and dichotomized at the 0.80 threshold (values ≤0.80 considered diseased; values >0.80 nondiagnostic for ischemia). Stenosis on CCTA was recorded at the 50% threshold (stenoses ≥50% considered obstructive and <50% as non-significant). Prespecified primary endpoint was expected to be greater than 70% of the lower bound of the 95% confidence interval.

Secondary Outcome Measures

1. Diagnostic Performance of CCTA Plus FFRCT at the Subject Level [1 day]

   Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CCTA plus CT-FLOW at the subject level using binary outcomes when compared to FFR as the reference standard.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age >18 years

• Patients providing written informed consent

• Scheduled to undergo clinically-indicated non-emergent invasive coronary angiography (ICA)

• Has undergone >64 multidetector row CCTA within 60 days prior to ICA

• No cardiac interventional therapy between the CCTA and ICA

Exclusion Criteria:

• Prior coronary artery bypass graft (CABG) surgery

• Prior percutaneous coronary intervention (PCI) for which suspected coronary artery lesion(s) are within a stented coronary vessel

• Contraindication to adenosine, including 2nd or 3rd degree heart block; sick sinus syndrome; long QT syndrome; severe hypotension, severe asthma, , severe COPD or bronchodilator-dependent COPD

• Suspicion of acute coronary syndrome (acute myocardial infarction and unstable angina)

• Recent prior myocardial infarction within 40 days of ICA

• Known complex congenital heart disease

• Prior pacemaker or internal defibrillator lead implantation

• Prosthetic heart valve

• Significant arrhythmia or tachycardia

• Impaired chronic renal function (serum creatinine >1.5 mg/dl

• Patients with known anaphylactic allergy to iodinated contrast

• Pregnancy or unknown pregnancy status

• Body mass index >35

• Patient requires an emergent procedure

• Evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, and severe congestive heart failure (NYHA III or IV) or acute pulmonary edema

• Any active, serious, life-threatening disease with a life expectancy of less than 2 months

• Inability to comply with study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Spring Hill Hospital	Mobile	Alabama	United States	36608

Sponsors and Collaborators

• HeartFlow, Inc.
• Baim Institute for Clinical Research
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Minneapolis Heart Institute Foundation

Investigators

• Principal Investigator: James K Min, MD, FACC, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Min JK, Berman DS, Budoff MJ, Jaffer FA, Leipsic J, Leon MB, Mancini GB, Mauri L, Schwartz RS, Shaw LJ. Rationale and design of the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic AngiOgraphy) study. J Cardiovasc Comput Tomogr. 2011 Sep-Oct;5(5):301-9. doi: 10.1016/j.jcct.2011.08.003. Epub 2011 Aug 7.

• Responsible Party: HeartFlow, Inc.
• ClinicalTrials.gov Identifier: NCT01233518
• Other Study ID Numbers: CP-901-001
• First Posted: Nov 3, 2010
• Last Update Posted: Feb 9, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by HeartFlow, Inc.: CCTA Coronary Artery Disease CAD
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease

Study Results

Participant Flow

Arm/Group Title	Single Arm Study
Arm/Group Description	Patients will receive cCTA, ICA, FFR, and cFFR per protocol. FFR: Fractional flow reserve measured during cardiac catheterization
Period Title: Overall Study
STARTED	285
COMPLETED	252
NOT COMPLETED	33

Baseline Characteristics

Arm/Group Title	Single Arm Study
Arm/Group Description	Patients will receive cCTA, ICA, FFR, and cFFR per protocol. FFR: Fractional flow reserve measured during cardiac catheterization
Overall Participants	252
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	135 53.6%
>=65 years	117 46.4%
Sex: Female, Male (Count of Participants)
Female	74 29.4%
Male	178 70.6%
Region of Enrollment (Count of Participants)
United States	92 36.5%
Belgium	43 17.1%
Canada	1 0.4%
Latvia	41 16.3%
South Korea	75 29.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Diagnostic Accuracy of CCTA Plus FFRCT and CCTA Alone
Description	Diagnostic accuracy of CCTA (Cardiac Computed Tomography Angiography) plus FFRCT (Noninvasive Fractional Flow Reserve computed from CCTA) to determine presence or absence of at least one hemodynamically (HD)-significant coronary artery stenosis* at the subject level using binary outcomes when compared to invasive FFR (Fractional Flow Reserve) as the reference standard. In the per-patient analysis, vessels with the most adverse clinical status were selected to represent a given patient. FFR and FFRCT measurements were recorded on a continuous scale and dichotomized at the 0.80 threshold (values ≤0.80 considered diseased; values >0.80 nondiagnostic for ischemia). Stenosis on CCTA was recorded at the 50% threshold (stenoses ≥50% considered obstructive and <50% as non-significant). Prespecified primary endpoint was expected to be greater than 70% of the lower bound of the 95% confidence interval.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Study
Arm/Group Description	Per-patient performance (diagnostic accuracy) CCTA plus FFRCT
Measure Participants	252
Accuracy of FFRCT	73 29%
Accuracy of CCTA	64 25.4%

2. Secondary Outcome

Title	Diagnostic Performance of CCTA Plus FFRCT at the Subject Level
Description	Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CCTA plus CT-FLOW at the subject level using binary outcomes when compared to FFR as the reference standard.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Study
Arm/Group Description	Patients will receive cCTA, ICA, FFR, and cFFR per protocol. FFR: Fractional flow reserve measured during cardiac catheterization
Measure Participants	252
Sensitivity	90 35.7%
Specificity	54 21.4%
Positive predictive value	67 26.6%
Negative predictive value	84 33.3%

Adverse Events

Arm/Group Title	Single Arm Study
Arm/Group Description	Patients will receive cCTA, ICA, FFR, and cFFR per protocol. FFR: Fractional flow reserve measured during cardiac catheterization
All Cause Mortality
	Single Arm Study
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm Study
	Affected / at Risk (%)	# Events
Total	2/252 (0.8%)
Blood and lymphatic system disorders
Septic shock	1/252 (0.4%)	1
Vascular disorders
Retroperitoneal bleed	1/252 (0.4%)	1
Hypotension	1/252 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Single Arm Study
	Affected / at Risk (%)	# Events
Total	0/252 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.