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

• ClinicalTrials.gov Identifier: NCT03054870
• Recruitment Status: Terminated
• First Posted: February 16, 2017
• Results First Posted: September 24, 2021
• Last Update Posted: September 24, 2021
• Sponsor: Cyclomedica Australia PTY Limited
• Information provided by (Responsible Party): Cyclomedica Australia PTY Limited

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lung Structure Determination	Drug: Xe-133; Drug: Technegas	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 226 participants
• Allocation: N/A
• Intervention Model: Crossover Assignment
• Intervention 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)
• Masking Description: 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.
• Primary Purpose: Other
• Official Title: A Comparison of Technegas® and Xenon 133 Planar Lung Imaging in Subjects Referred for Ventilation Scintigraphy
• Actual Study Start Date: September 1, 2017
• Actual Primary Completion Date: September 18, 2020
• Actual Study Completion Date: November 23, 2020

Arms and Interventions

Arm

Intervention/treatment

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.

Drug: Xe-133; Xe-133 ventilation scintigraphy; Other Names: Xenon-133; Xenon gas; Drug: Technegas; Technegas ventilation scintigraphy; Other Name: Technetium-99m labeled carbon particles

Outcome Measures

Primary Outcome Measures :

1. Blinded Readers Percent Agreement (PA) for Matching Image Views [ Time Frame: 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, 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%.

Secondary Outcome Measures :

1. Blinded Readers Percent Agreement (PA) for All Image Views [ Time Frame: 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.
2. Percent Agreement Measuring Inter-observer Agreement [ Time Frame: 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 (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.
3. Kappa Statistics Between Pairs of Blinded Readers by Lung Region [ Time Frame: 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). ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Morton Plant Hospital

Clearwater, Florida, United States, 33756

Mayo Clinic in Jacksonville, FL

Jacksonville, Florida, United States, 32224

United States, Illinois

Loyola University Medical Center

Maywood, Illinois, United States, 60153

United States, Missouri

Washington University Medical Center, Barnes-Jewish Hospital - Center for Advanced Medicine

Saint Louis, Missouri, United States, 63110

United States, North Carolina

Duke University Hospital

Durham, North Carolina, United States, 27710

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Houston Methodist Hospital

Houston, Texas, United States, 77030

Scott & White Medical Center

Temple, Texas, United States, 76508

United States, Utah

University of Utah Health Science Center

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Cyclomedica Australia PTY Limited

Investigators

• Study Director: Edward M Aten, MD; Certus International, Inc.

  Study Documents (Full-Text)

Documents provided by Cyclomedica Australia PTY Limited:

Study Protocol and Statistical Analysis Plan: Original Prototocol  [PDF] October 4, 2016

Study Protocol and Statistical Analysis Plan: Protocol Amendment 1  [PDF] November 2, 2018

Statistical Analysis Plan: Addendum for Statistical Analysis Plan  [PDF] July 30, 2020

More Information

• Responsible Party: Cyclomedica Australia PTY Limited
• ClinicalTrials.gov Identifier: NCT03054870
• Other Study ID Numbers: CYC-009
• First Posted: February 16, 2017
• Results First Posted: September 24, 2021
• Last Update Posted: September 24, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cyclomedica Australia PTY Limited:

pulmonary ventilation; ventilation scintigraphy

Additional relevant MeSH terms:

Xenon; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs