Trial Outcomes & Findings for The Value of CT Fractional Flow Reserve (NCT NCT03026283)

Last Updated: 2023-05-30

Results Overview

To evaluate sensitivity, specificity, positive and negative predictive value for FFR-CT after CCTA vs. CCTA alone, using invasive FFR as the gold standard.

Recruitment status

COMPLETED

Target enrollment

586 participants

Primary outcome timeframe

Up to 1 year from the study initiation will be required to enroll all study patients and obstain invasive and noninvasive FFR.

Results posted on

2023-05-30

Participant Flow

From 1/24/2017 to 6/13/2018 patients seen in the Cardiology ambulatory care service for CCTA to be evaluated for the diagnosis of obstructive disease, and who were evaluated as low to intermediate risk for obstructive disease, and who were symptomatic were offered the opportunity to participate in the study.

To participate, patients were required to complete the CCTA, and on exam have no Cardiac stenting or bypasses as determined by medical history provided by the patient and review of CCTA scan.

Participant milestones

Participant milestones
Measure	Initial CCTA All patients who consent will receive CCTA and medically acceptable care based on commonly accepted standards of care, and the patient's condition. The results of the CCTA will determine whether the patient receives FFR-CT or optimal medical care.	Optimal Medical Care After CCTA Patients who receive a CCTA and for whom the results are normal or less than 30% obstructive disease, will be recommended for optimal medical care. This care is the commonly accepted standard of care as recommended by the patient's referring physician. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	FFR-CT After CCTA Patients for whom CCTA results show 30% of more obstructive disease will be referred for FFR-CT. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	Optimal Medical Care After FFR-CT Patients with negative FFR-CT and CCTA results showing 30 to 49% obstructive disease will be recommended for optimal medical care with their Cardiologist, and patients with positive FFR-CT and CCTA results showing 30 to 49% obstructive disease will be recommended for stress testing. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	Stress Testing After FFR-CT Patients with 50% to 69% obstructive disease on CCTA and negative FFR-CT will be recommended for stress testing. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	ICA/Diagnostic Catheterization After FFR-CT Patients with 50 to 69% obstructive disease and positive FFR-CT will be referred for diagnostic catheterization and patients with 70% obstructive disease or greater by CCTA will be referred for diagnostic catheterization. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	Optimal Care After Stress Test Patients who undergo stress testing will be referred to optimal medical care if the results are negative. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).
CCTA Diagnosis STARTED	586	0	0	0	0	0	0
CCTA Diagnosis COMPLETED	572	0	0	0	0	0	0
CCTA Diagnosis NOT COMPLETED	14	0	0	0	0	0	0
Optimal Medical Care/FFR-CT Diagnosis STARTED	0	289	280	0	0	0	0
Optimal Medical Care/FFR-CT Diagnosis COMPLETED	0	286	265	0	0	0	0
Optimal Medical Care/FFR-CT Diagnosis NOT COMPLETED	0	3	15	0	0	0	0
Optimal Care/Stress Test/ICA STARTED	0	0	0	128	52	101	0
Optimal Care/Stress Test/ICA COMPLETED	0	0	0	108	14	73	0
Optimal Care/Stress Test/ICA NOT COMPLETED	0	0	0	20	38	28	0
Optimal Care/ICA Diagnostic Cath STARTED	0	0	0	0	0	0	21
Optimal Care/ICA Diagnostic Cath COMPLETED	0	0	0	0	0	0	21
Optimal Care/ICA Diagnostic Cath NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Initial CCTA All patients who consent will receive CCTA and medically acceptable care based on commonly accepted standards of care, and the patient's condition. The results of the CCTA will determine whether the patient receives FFR-CT or optimal medical care.	Optimal Medical Care After CCTA Patients who receive a CCTA and for whom the results are normal or less than 30% obstructive disease, will be recommended for optimal medical care. This care is the commonly accepted standard of care as recommended by the patient's referring physician. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	FFR-CT After CCTA Patients for whom CCTA results show 30% of more obstructive disease will be referred for FFR-CT. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	Optimal Medical Care After FFR-CT Patients with negative FFR-CT and CCTA results showing 30 to 49% obstructive disease will be recommended for optimal medical care with their Cardiologist, and patients with positive FFR-CT and CCTA results showing 30 to 49% obstructive disease will be recommended for stress testing. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	Stress Testing After FFR-CT Patients with 50% to 69% obstructive disease on CCTA and negative FFR-CT will be recommended for stress testing. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).	ICA/Diagnostic Catheterization After FFR-CT Patients with 50 to 69% obstructive disease and positive FFR-CT will be referred for diagnostic catheterization and patients with 70% obstructive disease or greater by CCTA will be referred for diagnostic catheterization. (The referring physician will make all treatment decisions, and may not follow the recommendation provided by the study team).
CCTA Diagnosis CCTA not performed as planned	9	0	0	0	0	0
CCTA Diagnosis Withdrawal by Subject	5	0	0	0	0	0
Optimal Medical Care/FFR-CT Diagnosis Screen Failure: Enrollment Criteria	0	3	0	0	0	0
Optimal Medical Care/FFR-CT Diagnosis FFRCT Nondiagnostic	0	0	15	0	0	0
Optimal Care/Stress Test/ICA Referring MD ordered diagnostic cath	0	0	0	8	11	0
Optimal Care/Stress Test/ICA Lost to Follow-up	0	0	0	9	2	2
Optimal Care/Stress Test/ICA Referring MD ordered stress test	0	0	0	2	0	7
Optimal Care/Stress Test/ICA Withdrawal by Subject	0	0	0	1	0	0
Optimal Care/Stress Test/ICA Referring MD used only optimal med care	0	0	0	0	25	19

Baseline Characteristics

Height and weight data was not recorded on enrollment for one participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1: HeartFlow CT-FFR Arm n=569 Participants All patients who consent will receive HeartFlow CT-FFR and medically acceptable care based on the study protocol, commonly accepted standards of care, and the patients condition. HeartFLow CT-FFR: Patients receiving CCTA to diagnose stable chest pain or stable angina will receive CT-FFR to estimate rate of flow through the coronary arteries. The rate of flow will be compared to the rate found on Invasive FFR (the gold standard) if the subject receives invasive FFR.
Age, Continuous	62.2 years STANDARD_DEVIATION 12.7 • n=569 Participants
Sex: Female, Male Female	289 Participants n=569 Participants
Sex: Female, Male Male	280 Participants n=569 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	72 Participants n=569 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	497 Participants n=569 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=569 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=569 Participants
Race (NIH/OMB) Asian	59 Participants n=569 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=569 Participants
Race (NIH/OMB) Black or African American	79 Participants n=569 Participants
Race (NIH/OMB) White	295 Participants n=569 Participants
Race (NIH/OMB) More than one race	136 Participants n=569 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=569 Participants
Indication Angina (Typical)	62 Participants n=569 Participants
Indication Angina (Atypical)	284 Participants n=569 Participants
Indication Noncardiac Chest Pain	1 Participants n=569 Participants
Indication Dyspnea	170 Participants n=569 Participants
Indication Angina Status Unknown	2 Participants n=569 Participants
Indication Angina Status None	50 Participants n=569 Participants
Body Mass Index (BMI)	28.23 kg per meters squared STANDARD_DEVIATION 6.15 • n=568 Participants • Height and weight data was not recorded on enrollment for one participant.
Diabetes	117 Participants n=566 Participants • Three study participants did not respond when asked if they were diabetic.
Hypertension	337 Participants n=567 Participants • Two participants were unable to report whether they had been diagnosed and were being treated for hypertension,
Hyperlipidemia	312 Participants n=564 Participants • Five study participants were unable to report upon enrollment whether they had been diagnosed with hyperlipidemia.
Smoking History Never Smoked	364 Participants n=560 Participants • 9 Participants did not disclosed their smoking history.
Smoking History Former Smoker	157 Participants n=560 Participants • 9 Participants did not disclosed their smoking history.
Smoking History Current Smoker	39 Participants n=560 Participants • 9 Participants did not disclosed their smoking history.

PRIMARY outcome

Timeframe: Up to 1 year from the study initiation will be required to enroll all study patients and obstain invasive and noninvasive FFR.

Population: All patients who received FFR-CT and Diagnostic Catheterization.

To evaluate sensitivity, specificity, positive and negative predictive value for FFR-CT after CCTA vs. CCTA alone, using invasive FFR as the gold standard.

Outcome measures

Outcome measures
Measure	CCTA n=97 Participants .CCTA Alone	FFR-CT After CCTA n=97 Participants FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Comparison of CCTA Alone to FFR-CT After CCTA Sensitivity	90.97 percent Interval 79.7 to 96.62	92.73 percent Interval 82.41 to 97.98	—
Comparison of CCTA Alone to FFR-CT After CCTA Specifcity	22.86 percent Interval 10.42 to 40.14	69.71 percent Interval 46.49 to 80.25	—
Comparison of CCTA Alone to FFR-CT After CCTA Positive Predictive Value	64.47 percent Interval 52.66 to 75.12	80.95 percent Interval 69.09 to 89.75	—
Comparison of CCTA Alone to FFR-CT After CCTA Negative Predictive Value	60.67 percent Interval 49.75 to 70.87	84.62 percent Interval 65.13 to 95.64	—

SECONDARY outcome

Timeframe: Up to 1 year will be required to obtain all reader evaluations for the study in order to asses inter-observer reliability.

Population: All patients who received CCTA, for whom scans were available for clinical review and review by the study's expert reader.

To evaluate differences in performance of readers of CCTA and CT-FFR based on years of experience. CCTA results were documented by the official reader, all of whom had less than 9 years experience reading CCTA. Independently the exams were reviewed by a second reader with more than 10 years experience reading CCTA. Due to an operational error, for 5 of the 572 cases that received CCTA, the detailed data was removed from the server before the second read. Therefore these cases were excluded from this analysis.

Outcome measures

Outcome measures
Measure	CCTA n=567 CCTA Scans .CCTA Alone	FFR-CT After CCTA FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Inter-observer Reliability: Assessment of All Cases	67.72 percent agreement Standard Error 0.0247	—	—

SECONDARY outcome

Timeframe: Up to 1 year will be required to obtain all reader evaluations for the study in order to asses inter-observer reliability.

Population: The less experienced reader read 271 of the CCTA scan as having Mild disease -- 30% obstructive disease or more. We compared these reading to the expert reader's assessment for the same cases.

To evaluate differences in performance of readers of CCTA and CT-FFR based on years of experience when assessing cases on which the official reading identified at least mild disease. Mild disease is defined as cases with 30% or more stenosis documented on CCTA reading. CCTA cases that cannot be read are treated as severe.)

Outcome measures

Outcome measures
Measure	CCTA n=271 Participants .CCTA Alone	FFR-CT After CCTA FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Inter - Observer Reliability: Assessment of at Least Mild Disease (30% Stenosis or More)	35.79 percent agreement Standard Error 0.0262	—	—

SECONDARY outcome

Timeframe: Up to 1 year will be required to obtain all reader evaluations for the study in order to asses inter-observer reliability.

Population: The less experienced reader called moderate stenosis or higher (50% or more stenosis) on 159 cases.

To evaluate differences in performance of readers of CCTA and CT-FFR based on years of experience when assessing cases on which the official reading is at least moderate (50% stenosis on CCTA. CCTA cases that cannot be read are treated as severe.

Outcome measures

Outcome measures
Measure	CCTA n=159 Participants .CCTA Alone	FFR-CT After CCTA FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Inter - Observer Reliability: Assessment of at Least Moderate Disease (50% Stenosis or More on CCTA)	40.88 percent agreement Standard Error 0.0385	—	—

SECONDARY outcome

Timeframe: Up to 1 year will be required to obtain all reader evaluations for the study in order to asses inter-observer reliability.

Population: The population of patients expected to have severe of more (70% obstructive disease or more) on CCTA by less experienced reader interpretation.

To evaluate differences in performance of readers of CCTA and CT-FFR based on years of experience when assessing cases with suspected severe disease on the official reading. (CCTAs that cannot be read are treated as severe).

Outcome measures

Outcome measures
Measure	CCTA n=83 Participants .CCTA Alone	FFR-CT After CCTA FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Inter - Observer Reliability: Assessment of Severe Disease is Diagnosesed on Official Read (70% or Greater)	51.81 percent agreement Standard Error 0.0422	—	—

SECONDARY outcome

Timeframe: Up to 15 months will be required to collect 90 day follow up information on all study participants.

To identify factors influencing return visits within 90 days for all patients enrolled who received CCTA. While we are not aware of any documented incremental risks for adding FFR-CT to the evaluation process of coronary artery disease, this safety measure was designed to identify and evaluate all unplanned return events to ensure that they were not related to FFR-CT or to flaws in study design or operations.

Outcome measures

Outcome measures
Measure	CCTA n=572 Participants .CCTA Alone	FFR-CT After CCTA FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Return Visits Direct Admit from CCTA	4 Participants	—	—
Return Visits Urgent/Unplanned return within 90 days	11 Participants	—	—
Return Visits No Unplanned/Urgent returns in 90 days	557 Participants	—	—

SECONDARY outcome

Timeframe: Up to 15 months will be required to collect 90 day follow up information on all study participants.

Population: Overall 15/572 (2.6%) patients returned for emergent visits. All outcomes may be viewed as being consistent with the diagnoses provided with CCTA and FFR-CT.

To identify factors influencing return visits within 90 days. All patient's who returned to the ED within 90 days of their initial visit were contacted for follow up. All their medical records were reviewed.

Outcome measures

Outcome measures
Measure	CCTA n=11 Participants .CCTA Alone	FFR-CT After CCTA n=2 Participants FFR-CT After CCTA	Referred for Optimla Medical Care After CCTA n=2 Participants These patients were referred to optimal medical care after CCTA. They returned to the Emergency Department with Chest Pain and were discharged after evaluation and noninvasive treatment.
Return Visits -- Reasons for Return Severe Disease Received Intervention	11 Participants	0 Participants	0 Participants
Return Visits -- Reasons for Return Nonobstructive Disease Went to Cardiac Cath	0 Participants	1 Participants	0 Participants
Return Visits -- Reasons for Return Nonobstructive Disease Discharged from ED	0 Participants	1 Participants	2 Participants

Adverse Events

Patients Referred for Cardiac Intervention

Serious events: 1 serious events

Other events: 0 other events

Deaths: 2 deaths

Patients Referred for Stress Tesing

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Patients Referred for Optimal Medical Care

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Patients Referred for Cardiac Intervention n=101 participants at risk Patients for whom Cardiac Catheterization was recommended after protocol testing.	Patients Referred for Stress Tesing n=73 participants at risk Patients for whom stress testing was recommended after FFR-CT	Patients Referred for Optimal Medical Care n=398 participants at risk Patients for whom optimal medical care was recommended after protocol testing.
Cardiac disorders Percutaneous Coronary Intevention	0.99% 1/101 • Number of events 1 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.	1.4% 1/73 • Number of events 1 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.	0.00% 0/398 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.

Other adverse events

Other adverse events
Measure	Patients Referred for Cardiac Intervention n=101 participants at risk Patients for whom Cardiac Catheterization was recommended after protocol testing.	Patients Referred for Stress Tesing n=73 participants at risk Patients for whom stress testing was recommended after FFR-CT	Patients Referred for Optimal Medical Care n=398 participants at risk Patients for whom optimal medical care was recommended after protocol testing.
Cardiac disorders Diagnostic Catheterization	0.00% 0/101 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.	0.00% 0/73 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.	0.25% 1/398 • Number of events 1 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.
Cardiac disorders Return to ED for Chest Pain	0.00% 0/101 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.	2.7% 2/73 • Number of events 2 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.	0.25% 1/398 • Number of events 1 • 90 days from the imaging encounter. Serious adverse events were major cardiac events (Acute Myocardial Infarction, death or emergency cardiac intervention). Other adverse events unnecessary exposure to invasive testing or higher risk health care environment, such as return to ED or unexpected referrals to diagnostic cardiac cath.

Additional Information

Pamela Noack

Northwell Health

Phone: 212 434 4926

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place