A Comparison of Technegas and Xenon-133 Planar Lung Imaging in Subjects Referred for Ventilation Scintigraphy

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Comparison of Technegas® and Xenon 133 Planar Lung Imaging in Subjects Referred for Ventilation Scintigraphy

Conditions
-----------------
Lung Structure Determination

Intervention / Treatment
-----------------
* Drug: Xe-133
* Drug: Technegas


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subject at least 18 years of age. Subject is a candidate for ventilation imaging. Subject must be willing and able to provide informed consent. Subject must be stable and able to undergo Xe-133 planar imaging and Technegas planar imaging. Subject must be willing and agree to complete study procedures. Subject is using adequate birth control, if female and fertile. Adequate birth control is defined as surgical sterilization, hormone contraceptive use or intrauterine device (IUD). Female subject of child-bearing potential has a negative urine or serum pregnancy test. Subject has had or is scheduled to have a chest X-ray within 24 hours prior to the investigational imaging study. Exclusion Criteria: Subject has been administered any other radiopharmaceutical within a timeframe that might cause interference with study imaging. Subject is a pregnant or lactating female. Subject has received Technegas in the past. Subject has received an investigational drug within 30 days prior to dosing. Subject is hemodynamically unstable.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects will undergo standard of care Xe-133 ventilation scintigraphy per medical needs followed by investigational Technegas ventilation scintigraphy per protocol.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Xe-133 Followed by Technegas<br>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. | Drug: Xe-133<br>* Xe-133 ventilation scintigraphy<br>* Other names: Xenon gas;Drug: Technegas<br>* Technegas ventilation scintigraphy<br>* Other names: Technetium-99m labeled carbon particles;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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). | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pulmonary ventilation, ventilation scintigraphy