Trial Outcomes & Findings for Diagnostic Accuracy of On-line Quantitative Flow Ratio (QFR). FAVOR II Europe-Japan (NCT NCT02959814)

NCT ID: NCT02959814

Last Updated: 2020-01-13

Results Overview

Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80. Positive DS% is defined as DS% \> 50%

• Recruitment status: COMPLETED
• Target enrollment: 329 participants
• Primary outcome timeframe: 1 hour
• Results posted on: 2020-01-13

Participant Flow

Participant milestones

Measure	Patients With Paired QFR, FFR and 2D-QCA Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Overall Study STARTED	329
Overall Study COMPLETED	272
Overall Study NOT COMPLETED	57

Reasons for withdrawal

Measure	Patients With Paired QFR, FFR and 2D-QCA Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Overall Study Excluded based on diagnostic angiography	16
Overall Study Excluded based on anatomical criteria	2
Overall Study Protocol Violation	7
Overall Study FFR not measured	2
Overall Study In-procedure QFR not computed	6
Overall Study Excluded by FFR core-lab	24

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Age, Continuous	67 years STANDARD_DEVIATION 10 • n=272 Participants
Sex: Female, Male Female	76 Participants n=272 Participants
Sex: Female, Male Male	196 Participants n=272 Participants

PRIMARY outcome

Timeframe: 1 hour

Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80. Positive DS% is defined as DS% > 50%

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Sensitivity: Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) Compared to Proportion of Patients With Positive Percentual Diameter Stenosis (DS%) Assessed by 2D QCA of FFR Positive Patients (True Positives) 2D-QCA	0.442 Proportion Interval 0.345 to 0.543
Sensitivity: Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) Compared to Proportion of Patients With Positive Percentual Diameter Stenosis (DS%) Assessed by 2D QCA of FFR Positive Patients (True Positives) QFR	0.865 Proportion Interval 0.784 to 0.924

PRIMARY outcome

Timeframe: 1 hour

Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80. Negative DS% is defined as DS% ≤ 50%.

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Specificity: Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) Compared to Proportion of Patients With Negative DS% Assessed by 2D QCA of FFR Negative Patients (True Negatives) 2D-QCA	0.765 Proportion Interval 0.703 to 0.82
Specificity: Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) Compared to Proportion of Patients With Negative DS% Assessed by 2D QCA of FFR Negative Patients (True Negatives) QFR	0.869 Proportion Interval 0.816 to 0.911

SECONDARY outcome

Timeframe: 1 hour

Population: Patients with successful FFR Measurement before Exclusion based on missing QFR and/or 2D-QCA

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=302 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility)	296 Participants

SECONDARY outcome

Timeframe: 1 hour

Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) (Sensitivity)	0.865 Proportion Interval 0.784 to 0.924

SECONDARY outcome

Timeframe: 1 hour

Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) (Specificity)	0.869 Proportion Interval 0.816 to 0.911

SECONDARY outcome

Timeframe: 1 hour

Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Proportion of Patients With Positive FFR (True Positives) of Patients With Positive QFR (Positive Predictive Value)	0.763 Proportion Interval 0.676 to 0.836

SECONDARY outcome

Timeframe: 1 hour

Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Proportion of Patients With Negative FFR (True Negatives) of Patients With Negative QFR (Negative Predictive Value)	0.930 Proportion Interval 0.885 to 0.961

SECONDARY outcome

Timeframe: 1 hour

Positive likelihood ratio is defined as sensitivity/(1-specificity). Negative likelihood ratio is defined as (1-sensitivty)/specificity

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio Negative likelihood ratio	0.16 Ratio Interval 0.09 to 0.25
Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio Positive likelihood ratio	6.60 Ratio Interval 4.62 to 9.37

SECONDARY outcome

Timeframe: 1 hour

QFR limits to yield 95% sensitivity and specificity. The QFR limits are identified by Area under the receiver operating curve analysis.

QFR limits are defined as the numerical QFR ratios (0-1.00).

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR 95% limit for sensitivity	0.77 Ratio
Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR 95% limit for specificity	0.87 Ratio

SECONDARY outcome

Timeframe: 1 hour

Comparison of proportion of participants correctly classified by QFR and 2D QCA using FFR as reference standard.

Diagnostic accuracy is defined as (true positives + false negatives) / (true positives+false positives+true negatives+false negatives).

Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80. Negative FFR is defines as FFR>0.80. Negative QFR is defines as QFR>0.80. Positive 2D QCA is defined as 2D-QCA % percent diameter stenosis >50. Negative 2D QCA is defined as 2D-QCA % diameter stenosis≤50.

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis) TIMI-FLOW based QFR	0.868 Proportion
Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis) 2D-QCA	0.659 Proportion

SECONDARY outcome

Timeframe: 1 day

Peri-procedural myocardial infarction

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Participants With Myocardial Infarction (Number of Patients)	0 Participants

SECONDARY outcome

Timeframe: 1 day

Peri-procedural mortality

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
All-cause Mortality (Number of Patients)	0 Participants

SECONDARY outcome

Timeframe: 1 hour

Time from starting preparations to do FFR (e.g. ordering assistants to prepare pressure wire, adenosine infusion etc.) to FFR value is obtained and drift has been verified to be within the prespecified limits

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Time to FFR	7.0 Minutes Interval 5.0 to 10.0

SECONDARY outcome

Timeframe: 1 hour

Time from first image evaluation on QFR computer until TIMI frame count based QFR value is obtained

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Time to QFR After Receiving Angiographic Images	5.0 Minutes Interval 3.5 to 6.1

SECONDARY outcome

Timeframe: 1 hour

Volume of contrast for total procedure

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Contrast Use	120 mL Standard Deviation 76

SECONDARY outcome

Timeframe: 1 hour

Fluoroscopy time for total procedure

Outcome measures

Measure	Patients With Paired QFR, FFR and 2D-QCA n=272 Participants Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria
Fluoroscopy Time	9.8 Minutes Standard Deviation 7.2

Adverse Events

Patients With Paired QFR, FFR and 2D-QCA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Niels Ramsing Holm, MD

Skejby University Hospital, Denmark

Phone: 004526849066

Email: Niels.holm@clin.au.dk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place