Trial Outcomes & Findings for A Comparison of Technegas and Xenon-133 Planar Lung Imaging in Subjects Referred for Ventilation Scintigraphy (NCT NCT03054870)

Last Updated: 2021-09-24

Results Overview

Three blinded readers independently assessed the Xe-133 and Technegas images in separate reading sessions. Readers were blinded to all clinical information except a subject's screening chest X-ray. Xe-133 images were obtained per site-specific standard of care. Technegas images included a 6-view image set, and the primary endpoint was based on assessment of the subset of views that matched the Xe-133 image views. At the start of each case-read, a reader visually divided each lung into 3 regions of approximately equal size arranged craniocaudally (apical, mid, and basal), 6 regions in total, and then assessed each lung region for ventilation according to a three-point scale: 0=absent ventilation, 1=decreased ventilation, 2=normal ventilation. At the unplanned interim stage, PA between the Xe-133 scores and Technegas scores was tested for non-inferiority at one-sided alpha=0.0141, equivalent to the lower bound of the 97.18% confidence interval exceeding 60%.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

226 participants

Primary outcome timeframe

The median duration of Technegas imaging was 22 minutes. Blinded reader assessments of images ranged from <1 month to 16 months following the imaging (median 5 months).

Results posted on

2021-09-24

Participant Flow

Participant milestones

Participant milestones
Measure	Xe-133 Followed by Technegas Subjects first inhaled active comparator Xe-133, approximately 10 to 30 millicuries (mCi), and ventilation planar scintigraphy was performed per site standard of care procedures for subject medical need. On the same day, following completion of Xe-133 imaging, subjects inhaled experimental Technegas (Technetium-99m labeled carbon particles), approximately 1.1 mCi, and ventilation planar scintigraphy was performed. Xe-133: Xe-133 ventilation scintigraphy Technegas: Technegas ventilation scintigraphy
Day of Ventilation Imaging STARTED	210
Day of Ventilation Imaging COMPLETED	205
Day of Ventilation Imaging NOT COMPLETED	5
24-hour Follow-up STARTED	118
24-hour Follow-up COMPLETED	118
24-hour Follow-up NOT COMPLETED	0
Blinded Read of Images STARTED	200
Blinded Read of Images COMPLETED	200
Blinded Read of Images NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Xe-133 Followed by Technegas Subjects first inhaled active comparator Xe-133, approximately 10 to 30 millicuries (mCi), and ventilation planar scintigraphy was performed per site standard of care procedures for subject medical need. On the same day, following completion of Xe-133 imaging, subjects inhaled experimental Technegas (Technetium-99m labeled carbon particles), approximately 1.1 mCi, and ventilation planar scintigraphy was performed. Xe-133: Xe-133 ventilation scintigraphy Technegas: Technegas ventilation scintigraphy
Day of Ventilation Imaging Protocol Violation	4
Day of Ventilation Imaging Lost to Follow-up	1

Baseline Characteristics

4 participants had unknown weight or height

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xe-133 Followed by Technegas n=210 Participants Subjects received the active comparator Xe-133 followed by inhalation of experimental Technegas on the same day.
Age, Continuous	60.4 years STANDARD_DEVIATION 13.93 • n=210 Participants
Sex: Female, Male Female	99 Participants n=210 Participants
Sex: Female, Male Male	111 Participants n=210 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=210 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	205 Participants n=210 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=210 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=210 Participants
Race (NIH/OMB) Asian	1 Participants n=210 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=210 Participants
Race (NIH/OMB) Black or African American	22 Participants n=210 Participants
Race (NIH/OMB) White	186 Participants n=210 Participants
Race (NIH/OMB) More than one race	0 Participants n=210 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=210 Participants
Body Mass Index	29.14 kilogram/meter squared STANDARD_DEVIATION 7.472 • n=206 Participants • 4 participants had unknown weight or height
Reason for Ventilation Imaging Suspected Pulmonary Embolism (PE) or Follow-up for PE · Yes	71 Participants n=210 Participants
Reason for Ventilation Imaging Suspected Pulmonary Embolism (PE) or Follow-up for PE · No	139 Participants n=210 Participants
Reason for Ventilation Imaging Chronic Obstructive Pulmonary Disease (COPD) · Yes	35 Participants n=210 Participants
Reason for Ventilation Imaging Chronic Obstructive Pulmonary Disease (COPD) · No	175 Participants n=210 Participants
Reason for Ventilation Imaging Pulmonary or Cystic Fibrosis · Yes	31 Participants n=210 Participants
Reason for Ventilation Imaging Pulmonary or Cystic Fibrosis · No	179 Participants n=210 Participants
Reason for Ventilation Imaging Pulmonary Hypertension · Yes	25 Participants n=210 Participants
Reason for Ventilation Imaging Pulmonary Hypertension · No	185 Participants n=210 Participants
Reason for Ventilation Imaging Pre or Post Lung Surgery Evaluation (Lung Transplant or Reduction) · Yes	97 Participants n=210 Participants
Reason for Ventilation Imaging Pre or Post Lung Surgery Evaluation (Lung Transplant or Reduction) · No	113 Participants n=210 Participants
Reason for Ventilation Imaging Other Reason · Yes	37 Participants n=210 Participants
Reason for Ventilation Imaging Other Reason · No	173 Participants n=210 Participants
Screening Chest X-Ray Interpretation Normal	67 Participants n=210 Participants
Screening Chest X-Ray Interpretation Abnormal	143 Participants n=210 Participants
Pleural Effusion Observed in Screening Chest X-Ray Yes	12 Participants n=210 Participants
Pleural Effusion Observed in Screening Chest X-Ray No	198 Participants n=210 Participants

PRIMARY outcome

Timeframe: The median duration of Technegas imaging was 22 minutes. Blinded reader assessments of images ranged from <1 month to 16 months following the imaging (median 5 months).

Population: Full Analysis Set (FAS) consisting of subjects who completed all of the ventilation imaging on the study, and both sets of Xe-133 planar scans and the Technegas planar scans were of interpretable image quality according to site Investigators' assessment.

Outcome measures

Outcome measures
Measure	Blinded Reader 03 n=200 Participants Blinded Reader 03's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 04 n=200 Participants Blinded Reader 04's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 05 n=200 Participants Blinded Reader 05's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.
Blinded Readers Percent Agreement (PA) for Matching Image Views	76.2 percentage of lung regions Interval 72.3 to 79.6	70.7 percentage of lung regions Interval 66.4 to 74.7	80.1 percentage of lung regions Interval 76.4 to 83.3

SECONDARY outcome

Timeframe: The median duration of Technegas imaging was 22 minutes. Blinded reader assessments of images ranged from <1 month to 16 months following the imaging (median 5 months).

Three blinded readers independently assessed the Xe-133 and Technegas images in separate reading sessions. Readers were blinded to all clinical information except a subject's screening chest X-ray. Xe-133 images were obtained per site-specific standard of care. Technegas images included a 6-view image set. Two sequential reads were conducted of each subject's Technegas images. In the first read, only views that matched the Xe-133 image views were presented and read, and assessments based on the matched views were used in the primary outcome measure. Immediately following the commitment of those assessments, all Technegas image views were presented to the reader, and a second assessment of all the Technegas image views was made using the same ventilation scoring metric as described for the primary outcome measure. The estimation of PA and its analyses were also the same as for the primary outcome measure.

Outcome measures

Outcome measures
Measure	Blinded Reader 03 n=200 Participants Blinded Reader 03's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 04 n=200 Participants Blinded Reader 04's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 05 n=200 Participants Blinded Reader 05's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.
Blinded Readers Percent Agreement (PA) for All Image Views	75.7 percentage of lung regions Interval 71.7 to 79.2	69.1 percentage of lung regions Interval 64.7 to 73.2	79.6 percentage of lung regions Interval 75.6 to 83.0

SECONDARY outcome

Timeframe: The median duration of Technegas imaging was 22 minutes. Blinded reader assessments of images ranged from <1 month to 16 months following the imaging (median 5 months).

Population: Full Analysis Set (FAS)

Percent agreement (PA) measuring inter-observer agreement between pairs of blinded readers for their ventilation scoring assessments within each of the three imaging groups: Xe-133, Technegas matched views, and Technegas all views. For each image set, a reader scored 6 regions of the lungs according to a three-point scale: 0=absent ventilation, 1=decreased ventilation, 2=normal ventilation; agreement between a pair of readers' assessments was based on the agreement of their ventilation scores by subject and lung region.

Outcome measures

Outcome measures
Measure	Blinded Reader 03 n=200 Participants Blinded Reader 03's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 04 n=200 Participants Blinded Reader 04's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 05 n=200 Participants Blinded Reader 05's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.
Percent Agreement Measuring Inter-observer Agreement Reader Pair 04, 05	79.6 percentage of lung regions Interval 76.1 to 82.7	73.9 percentage of lung regions Interval 70.0 to 77.4	73.4 percentage of lung regions Interval 69.4 to 77.1
Percent Agreement Measuring Inter-observer Agreement Reader Pair 03, 04	82.8 percentage of lung regions Interval 79.9 to 85.4	72.7 percentage of lung regions Interval 69.0 to 76.1	71.6 percentage of lung regions Interval 67.8 to 75.1
Percent Agreement Measuring Inter-observer Agreement Reader Pair 03, 05	80.4 percentage of lung regions Interval 76.9 to 83.5	81.2 percentage of lung regions Interval 78.1 to 84.0	80.8 percentage of lung regions Interval 77.6 to 83.7

SECONDARY outcome

Timeframe: The median duration of Technegas imaging was 22 minutes. Blinded reader assessments of images ranged from <1 month to 16 months following the imaging (median 5 months).

Population: Full Analysis Set (FAS)

By lung-region kappa statistics measuring inter-observer agreement between pairs of blinded readers for their ventilation scoring assessments within each of the three imaging groups: Xe-133, Technegas matched views, and Technegas all views. For each image set, a reader scored 6 regions of the lungs according to a three-point scale: 0=absent ventilation, 1=decreased ventilation, 2=normal ventilation. Kappa statistics for a pair of readers' assessments were derived from the frequencies of the cross-tabulation of the readers' ventilation scores by lung region. Kappa statistics are an index of inter-observer agreement corrected for chance with possible values ranging from -1 to 1, where 1 represents perfect agreement.

Outcome measures

Adverse Events

Xe-133 Followed by Technegas

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Xe-133 Followed by Technegas n=210 participants at risk Subjects first inhaled active comparator Xe-133, approximately 10 to 30 millicuries (mCi), and ventilation planar scintigraphy was performed per site standard of care procedures for subject medical need. On the same day, following completion of Xe-133 imaging, subjects inhaled experimental Technegas (Technetium-99m labeled carbon particles), approximately 1.1 mCi, and ventilation planar scintigraphy was performed.
Nervous system disorders Dizziness	0.95% 2/210 • Number of events 2 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
Nervous system disorders Dysgeusia	0.95% 2/210 • Number of events 2 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
General disorders Chills	0.48% 1/210 • Number of events 1 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
Musculoskeletal and connective tissue disorders Back pain	0.48% 1/210 • Number of events 1 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
Musculoskeletal and connective tissue disorders Muscle spasms	0.48% 1/210 • Number of events 1 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.48% 1/210 • Number of events 1 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.48% 1/210 • Number of events 1 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.
Skin and subcutaneous tissue disorders Night sweats	0.48% 1/210 • Number of events 1 • From the time of Informed Consent until study discharge. Under the original protocol discharge followed 24-hour follow-up. Under the amended protocol, 24-hour follow-up was removed and discharge followed study imaging.

Additional Information

James McBrayer

Cyclomedica Australia Pty Ltd

Phone: +61 2 9541 0411

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Blinded Reader 03 n=200 Participants Blinded Reader 03's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 04 n=200 Participants Blinded Reader 04's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.	Blinded Reader 05 n=200 Participants Blinded Reader 05's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on Matched image views.
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Apical: Pair 03, 04	0.479 Index of inter-reader agreement Interval 0.339 to 0.619	0.529 Index of inter-reader agreement Interval 0.428 to 0.63	0.503 Index of inter-reader agreement Interval 0.404 to 0.602
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Mid: Pair 03, 05	0.538 Index of inter-reader agreement Interval 0.408 to 0.669	0.560 Index of inter-reader agreement Interval 0.44 to 0.681	0.571 Index of inter-reader agreement Interval 0.457 to 0.685
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Mid: Pair 04, 05	0.527 Index of inter-reader agreement Interval 0.401 to 0.653	0.434 Index of inter-reader agreement Interval 0.332 to 0.535	0.421 Index of inter-reader agreement Interval 0.32 to 0.521
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Basal: Pair 03, 04	0.530 Index of inter-reader agreement Interval 0.416 to 0.644	0.466 Index of inter-reader agreement Interval 0.368 to 0.563	0.452 Index of inter-reader agreement Interval 0.355 to 0.549
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Apical: Pair 03, 04	0.665 Index of inter-reader agreement Interval 0.535 to 0.795	0.484 Index of inter-reader agreement Interval 0.389 to 0.58	0.495 Index of inter-reader agreement Interval 0.4 to 0.591
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Apical: Pair 03, 05	0.589 Index of inter-reader agreement Interval 0.464 to 0.713	0.621 Index of inter-reader agreement Interval 0.512 to 0.73	0.596 Index of inter-reader agreement Interval 0.484 to 0.708
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Apical: Pair 03, 05	0.500 Index of inter-reader agreement Interval 0.365 to 0.634	0.558 Index of inter-reader agreement Interval 0.446 to 0.67	0.589 Index of inter-reader agreement Interval 0.479 to 0.7
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Apical: Pair 04, 05	0.538 Index of inter-reader agreement Interval 0.406 to 0.671	0.481 Index of inter-reader agreement Interval 0.369 to 0.592	0.467 Index of inter-reader agreement Interval 0.36 to 0.573
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Mid: Pair 03, 04	0.551 Index of inter-reader agreement Interval 0.423 to 0.68	0.474 Index of inter-reader agreement Interval 0.371 to 0.577	0.509 Index of inter-reader agreement Interval 0.405 to 0.612
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Basal: Pair 03, 05	0.517 Index of inter-reader agreement Interval 0.401 to 0.633	0.553 Index of inter-reader agreement Interval 0.445 to 0.662	0.510 Index of inter-reader agreement Interval 0.399 to 0.621
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Left Lung Basal: Pair 04, 05	0.469 Index of inter-reader agreement Interval 0.35 to 0.588	0.424 Index of inter-reader agreement Interval 0.321 to 0.528	0.461 Index of inter-reader agreement Interval 0.359 to 0.564
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Apical: Pair 04, 05	0.581 Index of inter-reader agreement Interval 0.452 to 0.71	0.593 Index of inter-reader agreement Interval 0.49 to 0.696	0.559 Index of inter-reader agreement Interval 0.459 to 0.66
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Mid: 03, 04	0.583 Index of inter-reader agreement Interval 0.445 to 0.721	0.518 Index of inter-reader agreement Interval 0.412 to 0.624	0.464 Index of inter-reader agreement Interval 0.357 to 0.571
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Mid: 03, 05	0.478 Index of inter-reader agreement Interval 0.348 to 0.607	0.663 Index of inter-reader agreement Interval 0.554 to 0.772	0.682 Index of inter-reader agreement Interval 0.578 to 0.786
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Mid: 04, 05	0.511 Index of inter-reader agreement Interval 0.38 to 0.642	0.530 Index of inter-reader agreement Interval 0.426 to 0.634	0.515 Index of inter-reader agreement Interval 0.41 to 0.619
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Basal: 03, 04	0.486 Index of inter-reader agreement Interval 0.367 to 0.605	0.448 Index of inter-reader agreement Interval 0.353 to 0.543	0.427 Index of inter-reader agreement Interval 0.333 to 0.521
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Basal: 03, 05	0.479 Index of inter-reader agreement Interval 0.36 to 0.597	0.530 Index of inter-reader agreement Interval 0.418 to 0.642	0.533 Index of inter-reader agreement Interval 0.424 to 0.642
Kappa Statistics Between Pairs of Blinded Readers by Lung Region Right Lung Basal: 04, 05	0.519 Index of inter-reader agreement Interval 0.403 to 0.634	0.496 Index of inter-reader agreement Interval 0.395 to 0.597	0.509 Index of inter-reader agreement Interval 0.406 to 0.611