Trial Outcomes & Findings for Non-Contrast 4DCT to Detect Pulmonary Thromboembolic Events (NCT NCT03183063)

Results Overview

A custom automated PE detection algorithm will delineate hypo-perfused regions of interest (ROIs) on SPECT perfusion and ROIs on respiratory induced blood mass change (RIBMC) via SPECT/CT. Spatial overlap between hypo-perfused ROIs on SPECT perfusion (standard) and ROIs on RIBMC will be assessed using Dice similarity coefficient (DSC). Spearman correlation will be reported.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

139 participants

Primary outcome timeframe

1 hour

Results posted on

2020-06-05

Participant Flow

Participant milestones

Participant milestones
Measure	4DCT and SPECT/CT Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objective 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2, 3 and 4. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Overall Study STARTED	20	4	115
Overall Study COMPLETED	15	0	111
Overall Study NOT COMPLETED	5	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	4DCT and SPECT/CT Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for objective 1, 4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for objectives 2, 3 and 4. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Overall Study Withdrawal by Subject	2	0	0
Overall Study Physician Decision	3	4	4

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	4DCT and SPECT/CT n=15 Participants Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed from this cohort for outcomes 1, 4, and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Data will be analyzed from this cohort for outcome 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. Patients will be compared with Cohort 1 (4DCT and SPECT/CT) for objective 4 only.	4DCT With CTA in Suspected PE n=115 Participants Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. 62 with positive CTA results for PE and 62 with negative CTA results for PE will be included. Data will be analyzed from this cohort for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE	Total n=130 Participants Total of all reporting groups
Age, Continuous	53.8 years n=15 Participants	—	58.5 years n=115 Participants	57.433 years n=130 Participants
Sex: Female, Male Female	4 Participants n=15 Participants	—	64 Participants n=115 Participants	68 Participants n=130 Participants
Sex: Female, Male Male	11 Participants n=15 Participants	—	51 Participants n=115 Participants	62 Participants n=130 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	15 participants n=15 Participants	—	115 participants n=115 Participants	130 participants n=130 Participants

PRIMARY outcome

Timeframe: 1 hour

Population: Correlation coefficients were only calculated using the 15 subjects with documented PE in Cohort 1 (4DCT and SPECT/CT). All subjects in Cohort 2 (4DCT with BiPAP and SPECT/CT were withdrawn. Subjects in Cohort 3 (4DCT with CTA in suspected PE) were not analyzed for this outcome.

A custom automated PE detection algorithm will delineate hypo-perfused regions of interest (ROIs) on SPECT perfusion and ROIs on respiratory induced blood mass change (RIBMC) via SPECT/CT. Spatial overlap between hypo-perfused ROIs on SPECT perfusion (standard) and ROIs on RIBMC will be assessed using Dice similarity coefficient (DSC). Spearman correlation will be reported.

Outcome measures

Outcome measures
Measure	4DCT and SPECT/CT n=15 Participants Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Correlation of 4DCT Identified Perfusion With SPECT/CT Identified Perfusion	0.45 Spearman correlation Interval 0.18 to 0.61	—	—

PRIMARY outcome

Timeframe: 48 hours

Population: This outcome was analyzed for 51 subjects in Cohort 3 (4DCT with CTA in suspected PE) identified as PE positive by SPECT/CT. All subjects in Cohort 2 (4DCT with BiPAP and SPECT/T) were withdrawn. Subjects in Cohort 1 (4DCT and SPECT/CT) were not analyzed for this objective.

For each case, an automated PE detection algorithm will determine if functional deficits exist within CT-V and RIBMC. The patient will be classified as PE positive if the algorithm confirms the presence of two or more mismatched segmental or subsegmental defects between CT-V and RIBMC images. This CT-functional imaging (CT-FI) binary classification indicator will be acquired for each patient and compared to the result from the standard acquired CTA. Data will be reported as the count of participants determined to have PE by both imaging modalities (true positives, specificity).

Outcome measures

Outcome measures
Measure	4DCT and SPECT/CT Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE n=51 Participants Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Count of Participants With True Positive Detection of PE Using Contrast-free 4DCT Functional Imaging and SPECT/CT (Sensitivity)	—	—	40 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: This outcome was analyzed for 60 subjects in Cohort 3 (4DCT with CTA in suspected PE) identified as PE negative by CTA. All subjects in Cohort 2 (4DCT with BiPAP and SPECT/T) were withdrawn. Subjects in Cohort 1 (4DCT and SPECT/CT) were not analyzed for this objective.

For each case, an automated PE detection algorithm will determine if functional deficits exist within CT-V and RIBMC. The patient will be classified as PE negative if the algorithm cannot confirm the presence of two or more mismatched segmental or subsegmental defects between CT-V and RIBMC images. This CT-functional imaging (CT-FI) binary classification indicator will be acquired for each patient and compared to the result from the standard acquired CTA. Data will be reported as count of participants determined not to have PE by both imaging modalities (true negatives, sensitivity).

Outcome measures

Outcome measures
Measure	4DCT and SPECT/CT Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE n=60 Participants Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Count of Participants With True Negative Detection of PE Using Contrast-free 4DCT Functional Imaging (Specificity)	—	—	57 Participants

SECONDARY outcome

Timeframe: 1 hour

Population: Data was analyzed from the 15 participants in Cohort 1 (4DCT and SPECT/CT). All subjects were withdrawn from Cohort 2 (4DCT with BiPAP and SPECT/CT). Data was not analyzed for this objective for subjects in Cohort 3 (4DCT with CTA in suspected PE).

We will repeat the 4DCT process, obtaining two sets of images, and measure the change in radiographic tidal lung volume on RIBMC between the first and second 4DCT using data from subjects in Cohort 1 (4DCT and SPECT/T). Results are reported as percentage difference between the two scans.

Outcome measures

Outcome measures
Measure	4DCT and SPECT/CT n=15 Participants Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure and Correlate the 4DCT Re-imaging Variance in Radiographic Tidal Volume of RIBMC Images	14.84 percentage difference of volume Interval 2.6 to 37.63	—	—

SECONDARY outcome

Timeframe: 1 hour

Population: Data was analyzed from the 15 participants in Cohort 1 (4DCT and SPECT/CT). All subjects were withdrawn from Cohort 2 (4DCT with BiPAP and SPECT/CT). Data was not analyzed for this objective for subjects in Cohort 3 (4DCT with CTA in suspected PE).

We will repeat the 4DCT process, obtaining two sets of images, and measure the change in radiographic parenchymal lung mass on RIBMC between the first and second 4DCT using data from subjects in Cohort 1 (4DCT and SPECT/T). Results are reported as percentage difference between the two scans.

Outcome measures

Outcome measures
Measure	4DCT and SPECT/CT n=15 Participants Anticipated15 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. Both 4DCT scans will be obtained with normal breathing. Data will be analyzed for outcomes 1,4 and 5. 4DCT and SPECT/CT: Each patient will receive two 4DCT followed by SPECT/CT.	4DCT With BiPAP and SPECT/CT Anticipated 5 patients with segmental or lobar pulmonary emboli on CTA. Each will receive SPECT/CT and 4DCT imaging on the same day. The second of the two 4DCT scans will be obtained with positive airway breathing via BiPAP. Results in these patients will be analyzed for objective 6 only. 4DCT with BiPAP and SPECT/CT: Each patient will receive two 4DCT, with the second scan obtained with positive pressure breathing via BiPAP, followed by SPECT/CT. These patients will be analyzed for objective 4 only.	4DCT With CTA in Suspected PE Anticipated 124 participants with CTA ordered/performed for suspected PE will be enrolled to have 4DCT. Goal for analysis is 62 with positive CTA results for PE and 62 with negative CTA results for PE. Data will be analyzed for outcomes 2 and 3. 4DCT with CTA in suspected PE: Each patient will receive 4DCT before or after CTA for suspected PE
Measure and Correlate the 4DCT Re-imaging Variance in Parenchymal Lung Mass of RIBMC Images	18.23 percentage difference of mass Interval 0.6 to 38.32	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 hour

Population: Data from cohort 2 (4DCT with BiPAP and SPECT/CT) was to be analyzed for this outcome; however, all subjects were withdrawn. Data is not available from Cohorts 1 (4DCT and SPECT/CT) and 3 ($DCT with CTA in suspected PE) for this outcome measurement.

An automated PE detection algorithm will detect differences of hypo-perfused regions of interest (ROIs) on 4DCT and deficit ROIs on RIBMC with normal breathing versus positive pressure airway via BiPAP breathing using Dice similarity coefficient (DSC).

Outcome measures

Outcome data not reported

Adverse Events

4DCT and SPECT/CT

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

4DCT With BiPAP and SPECT/CT

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

4DCT With CTA in Suspected PE

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

Joanne Gondert

Beaumont Health

Phone: 248 551-0439

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place