Not provided
Not provided
Not provided
Not provided
Not provided
Trial met primary efficacy endpoint target. No additional subjects necessary.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Phase 3 within-subject non-inferiority trial of Technegas ventilation imaging compared to Xenon-133 (Xe-133) ventilation imaging to demonstrate the non-inferiority of Technegas compared to Xe-133 ventilation studies with respect to subject pulmonary ventilatory distribution. Subjects will undergo site-specific standard of care (SOC) Xe-133 imaging per medical needs followed by Technegas ventilation imaging per study protocol.
This is a Phase 3 within-subject non-inferiority trial of Technegas ventilation imaging compared to Xenon-133 (Xe-133) ventilation imaging to demonstrate the non-inferiority of Technegas compared to Xe-133 ventilation studies with respect to subject pulmonary ventilatory distribution. Subjects will undergo site-specific standard of care (SOC) Xe-133 imaging per medical needs followed by Technegas ventilation imaging per study protocol. Primary assessments of efficacy will be based on three blinded readers' assessments of the Technegas and Xe-133 ventilation images in independent reading sessions.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Xe-133 Followed by Technegas | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xe-133 | Drug | Xe-133 ventilation scintigraphy |
|
| Measure | Description | Time Frame |
|---|---|---|
| Blinded Readers Percent Agreement (PA) for Matching Image Views | 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%. | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Blinded Readers Percent Agreement (PA) for All Image Views | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Edward M Aten, MD | Certus International, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Morton Plant Hospital | Clearwater | Florida | 33756 | United States | ||
| Mayo Clinic in Jacksonville, FL |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39638430 | Derived | Parihar AS, Mhlanga JC, Royal HD, Siegel BA. Comparability of Quantifying Relative Lung Ventilation with Inhaled 99mTc-Technegas and 133Xe in Patients Undergoing Evaluation for Lung Transplantation. J Nucl Med. 2025 Jan 3;66(1):104-109. doi: 10.2967/jnumed.124.268801. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Day of Ventilation Imaging |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Original Prototocol | Oct 4, 2016 |
Not provided
Not provided
Subjects will undergo standard of care Xe-133 ventilation scintigraphy per medical needs followed by investigational Technegas ventilation scintigraphy per protocol.
Not provided
Not provided
Independent blinded readers will assess all ventilation scintigraphy images, masked as to subject identity and re-identified with a unique random code number (different code numbers for Xe-133 and Technegas images). The Xe-133 and Technegas images will be read in separate reading sessions in random order.
Not provided
| Technegas | Drug | Technegas ventilation scintigraphy |
|
|
| 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). |
| Percent Agreement Measuring Inter-observer Agreement | 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. | 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). |
| Kappa Statistics Between Pairs of Blinded Readers by Lung Region | 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. | 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). |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| Loyola University Medical Center | Maywood | Illinois | 60153 | United States |
| Washington University Medical Center, Barnes-Jewish Hospital - Center for Advanced Medicine | St Louis | Missouri | 63110 | United States |
| Duke University Hospital | Durham | North Carolina | 27710 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Houston Methodist Hospital | Houston | Texas | 77030 | United States |
| Scott & White Medical Center | Temple | Texas | 76508 | United States |
| University of Utah Health Science Center | Salt Lake City | Utah | 84132 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| 24-hour Follow-up |
|
| Blinded Read of Images |
|
Safety cohort - subjects who received any dose of Technegas
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Xe-133 Followed by Technegas | Subjects received the active comparator Xe-133 followed by inhalation of experimental Technegas on the same day. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Body Mass Index | 4 participants had unknown weight or height | Mean | Standard Deviation | kilogram/meter squared |
| ||||||||||||||||
| Reason for Ventilation Imaging | Subjects could have more than one reason checked for ventilation imaging. Suspected pulmonary embolism (PE) includes subjects presenting with chest pain, shortness of breath or dyspnea. In 58 cases pre-lung surgery evaluation was checked in addition to another lung disease category; in 39 cases lung surgery evaluation (pre or post) was the only reason checked. Generally, "Other" reason was checked in addition to one of the other specified categories | Count of Participants | Participants |
| |||||||||||||||||
| Screening Chest X-Ray | Screening chest X-ray was performed according to each site's standard of care prior to ventilation imaging. | Count of Participants | Participants |
| |||||||||||||||||
| Pleural Effusion Observed in Screening Chest X-Ray | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blinded Readers Percent Agreement (PA) for Matching Image Views | 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%. | 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. | Posted | Number | 97.18% Confidence Interval | percentage of lung regions | 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). |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Blinded Readers Percent Agreement (PA) for All Image Views | 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. | 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. | Posted | Number | 97.18% Confidence Interval | percentage of lung regions | 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). |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Agreement Measuring Inter-observer Agreement | 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of lung regions | 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). |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Kappa Statistics Between Pairs of Blinded Readers by Lung Region | 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | Index of inter-reader agreement | 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). |
|
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.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 210 | 0 | 210 | 7 | 210 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
|
Unblinded analysis of imaging efficacy data was to be done at completion of study and all blinded readings. Due to the COVID-19 pandemic impact on enrollment, FDA recommended an unplanned interim analysis be performed using blind read data from 200 subjects. Interim analysis was done by independent 3rd party statistician and reviewed by a Data Efficacy Monitoring Committee (DEMC), which recommended termination of the study based on positive results. Sponsor agreed.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| James McBrayer | Cyclomedica Australia Pty Ltd | +61 2 9541 0411 | clinicaltrials@cyclomedica.com |
| Apr 5, 2021 |
| Prot_SAP_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Protocol Amendment 1 | Nov 2, 2018 | Apr 5, 2021 | Prot_SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Addendum for Statistical Analysis Plan | Jul 30, 2020 | Apr 5, 2021 | SAP_002.pdf |
Not provided
| ID | Term |
|---|---|
| C000614978 | Xenon-133 |
| D054020 | Lasers, Gas |
| C056708 | Technegas |
| ID | Term |
|---|---|
| D007834 | Lasers |
| D055096 | Optical Devices |
| D004864 | Equipment and Supplies |
| D055618 | Radiation Equipment and Supplies |
Not provided
Not provided
|
| Unknown or Not Reported |
|
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| No |
|
| Chronic Obstructive Pulmonary Disease (COPD) |
|
|
| Pulmonary or Cystic Fibrosis |
|
|
| Pulmonary Hypertension |
|
|
| Pre or Post Lung Surgery Evaluation (Lung Transplant or Reduction) |
|
|
| Other Reason |
|
|
| Interpretation Abnormal |
|
|
| Non-Inferiority |
The non-inferiority margin was determined from a separate study where 6 blinded readers read and re-read 75 Xe-133 planar ventilation imaging studies in 2 read sessions separated by a minimum of 4 weeks. The readers scored the 6 regions of the lung using the same ventilation scoring metric used in this study. Based on analysis of the read/re-read results, 60% was established as a suitable margin for establishing the non-inferiority of Technegas compared to Xe-133. |
Binary agreement scores were analyzed for each reader separately using a generalized linear model with SAS® PROC GENMOD. The logit function (log odds ratio) was specified as the link function, and subject was specified as a repeated measure to allow for correlations between lung regions within a subject. The estimate of the intercept of the model using generalized estimating equation (GEE) methodology provided an overall estimate of the agreement and corresponding confidence interval in terms of the log odds ratio. Simple algebra was used to obtain the corresponding estimates and confidence intervals in terms of percent agreement (PA). For the study to be considered a success, the null hypothesis had to be rejected for at least 2 of the 3 blinded readers for the primary efficacy endpoint. |
| OG001 |
| Blinded Reader 04 |
Blinded Reader 04's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on All image views. |
| OG002 | Blinded Reader 05 | Blinded Reader 05's Percent Agreement between Xe-133 and Technegas Ventilation Scores based on All image views. |
|
|
|
Percent agreement (PA) between a pair of blinded readers ventilation lung scores based on assessment of all Technegas image views.
|
|
|
| OG002 | Technegas Kappa All Views | Kappa statistics for a pair of blinded readers ventilation lung scores based on assessment of all Technegas image views. |
|
|
|