Pulmonary Embolism
Conditions
Keywords
Pulmonary embolism, PE
Brief summary
Phase 3 within-subject trial of Technegas V/Q SPECT and Tc-99m macro-aggregated albumin (MAA) imaging compared to Xenon-133 V/Q planar and Tc-99m macroaggregate of albumin (MAA) imaging for the diagnosis of Pulmonary Embolism (PE).
Detailed description
This is a Phase 3 within-subject trial of Technegas Ventilation SPECT and Tc-99m MAA perfusion imaging compared to xenon (Xe-133) Ventilation Planar and Tc-99m MAA perfusion imaging for the diagnosis of PE. Diagnosis of PE provided by review of the subjects' documented clinical information after 30 days of follow-up. Primary assessments of efficacy will be based on an independent blind reads of the Technegas V/Q SPECT images by three different readers and the independent blind reads of Xe 133 V/Q planar images by three different readers.
Interventions
DRUGTechnegas V SPECT imaging
Technegas V SPECT imaging and Technetium 99m MAA Perfusion imaging for the diagnosis pf pulmonary embolism.
DRUGXenon-133 Ventilation Planar imaging
Xenon-133 Ventilation Planar imaging and Technetium 99m MAA Perfusion imaging for the diagnosis pf pulmonary embolism.
Sponsors
Cyclomedica Australia PTY Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects will be enrolled in Cohort 1 if they meet the following requirements: 1. Male or female, at least 18 years of age. 2. Suspected of having PE and be a candidate for Xe-133 V/Q imaging. 3. Willing and able to provide informed consent. 4. Stable and able to undergo Xe-133 planar imaging, Technegas SPECT imaging, and planar/SPECT perfusion imaging and complete follow-up procedures. 5. Willing and agree to complete study procedures, including follow-up safety assessments. 6. Using adequate birth control, if female and fertile. 7. If female, has a negative urine or serum pregnancy test. 8. Agrees to return for a 24-hour and 30 day follow-up safety assessment. Subjects will be enrolled in Cohort 2 if they meet the above criteria AND subject is likely to have pulmonary embolism based on one or more of the following: 1. Wells Score of 7 or greater. Subjects with a Wells Score less than 7 may be enrolled in Cohort 2 if there is agreement between the investigator and the medical monitor that the subject is at high risk for PE. 2. An abnormal D-dimer test. 3. Positive Doppler ultrasound for DVT. 4. CTA is positive for PE within 24 hours of this imaging study.
Exclusion criteria
Subject 1. Has undergone imaging with Iodine-131 (I-131) within 30 days, Thallium-201 (Tl-201) or Indium-111 (In-111) within 10 days, Fluorine 18 (F-18) within 24 hours, or any other radiopharmaceutical not otherwise specified within 72 hours of this imaging study. 2. Has previously undergone an imaging study with a Tc-99m agent, within 48 hours of this imaging study. 3. Is a pregnant or lactating female. 4. Has received Technegas in the past. 5. Was previously enrolled in another investigational study or received an investigational drug within 30 days prior to dosing. 6. Is hemodynamically unstable. 7. Has received therapeutic dose of low molecular weight or unfractionated heparin within 24 hours prior to dosing or Tissue Plasminogen Activator (tPA) within 4 hours prior to dosing or has received treatment for PE between the time of a positive CTA, if performed, and Technegas V/Q SPECT imaging.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of Technegas V/Q SPECT for the Diagnosis of PE | Prospective, 30 days follow-up | Compared to the sensitivity of Xenon V/Q Planar imaging. Truth based on blinded reader's assessments of V/Q SPECT images compared with subject's final diagnosis resulting from clinical information at 30 days follow-up. |
| Specificity of Technegas V/Q SPECT for the Diagnosis of PE. | Prospective, 30 days follow-up | Compared to the specificity of Xenon V/Q Planar imaging. Truth based on blinded reader's assessments of V/Q SPECT images compared with subject's final diagnosis resulting from clinical information at 30 days follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Predictive Value (NPV) of Imaging for Diagnosis of PE | Prospective, 30 days follow-up | NPV of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first. |
| Accuracy of Technegas V/Q SPECT and Xenon V/Q Planar Imaging for Diagnosis of PE | prospective, 30 days follow-up. | Accuracy of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first. |
| Safety of Technegas in Patients With Possible PE | Prospective, from enrollment through 30 days follow-up | Safety will be assessed by the incidence of treatment emergence adverse events and changes in clinical laboratory measurements, blood pressure, oxygen saturation, physical examination and pulmonary examination before and after treatment. |
| Likelihood Ratio for Diagnosis of PE | Prospective, 30 days follow-up | Likelihood ratios of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first. |
| Positive Predictive Value (PPV) of Imaging for Diagnosis of PE | Prospective, 30 days follow-up | PPV of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first. |
Countries
United States
Participant flow
Recruitment details
The recruitment period was November 14, 2012 to June 11, 2014. Subjects were recruited from US medical centers that performed Xenon-133 ventilation scans to evaluate patients for pulmonary embolism (PE).
Pre-assignment details
Subjects suspected of PE to have Xe-133 ventilation/Tc-99m macroaggregated albumin (MAA) perfusion (VQ) scan. Must have at least one within 72 hours before imaging: D-dimer, Doppler ultrasound for deep vein thrombosis (DVT) or computed tomography angiography (CTA) for PE. Not have therapeutic dose blood thinner for \> than 72 hrs prior to imaging.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Xenon-133 Ventilation Planar imaging, followed by Technegas Ventilation SPECT imaging with Technetium-99m (Tc-99m) labeled carbon particles, followed by Technetium 99m (Tc-99m) MAA Perfusion imaging for the diagnosis of pulmonary embolism. Xe-133 V / Tc-99m MAA Q results compared to Technegas V / Tc-99m MAA Q results. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Equipment issue | 1 |
| Overall Study | Inability to obtain subject blood sample | 1 |
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 59.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Sensitivity of Technegas V/Q SPECT for the Diagnosis of PE
Compared to the sensitivity of Xenon V/Q Planar imaging. Truth based on blinded reader's assessments of V/Q SPECT images compared with subject's final diagnosis resulting from clinical information at 30 days follow-up.
Time frame: Prospective, 30 days follow-up
Population: Pulmonary embolism adjudication was to be determined by an Independent Adjudication Committee for primary and secondary outcome data and blinded readings of Xe-133 and Technegas Ventilation and Tc-99m MAA Perfusion images were required for primary outcome data. Due to trial termination PE adjudication and blinded readings of images were not done.
Primary
Specificity of Technegas V/Q SPECT for the Diagnosis of PE.
Compared to the specificity of Xenon V/Q Planar imaging. Truth based on blinded reader's assessments of V/Q SPECT images compared with subject's final diagnosis resulting from clinical information at 30 days follow-up.
Time frame: Prospective, 30 days follow-up
Population: Pulmonary embolism adjudication was to be determined by an Independent Adjudication Committee for primary and secondary outcome data and blinded readings of Xe-133 and Technegas Ventilation and Tc-99m MAA Perfusion images were required for primary outcome data. Due to trial termination PE adjudication and blinded readings of images were not done.
Secondary
Accuracy of Technegas V/Q SPECT and Xenon V/Q Planar Imaging for Diagnosis of PE
Accuracy of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first.
Time frame: prospective, 30 days follow-up.
Population: PE adjudication for final clinical diagnosis was to be determined by an Independent Adjudication Committee and blinded readings of Xe-133 and Technegas Ventilation and Tc-99m MAA Perfusion images were required for primary and secondary outcome data. Due to trial termination PE adjudication and blinded readings of images were not done.
Secondary
Likelihood Ratio for Diagnosis of PE
Likelihood ratios of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first.
Time frame: Prospective, 30 days follow-up
Population: PE adjudication for final clinical diagnosis was to be determined by an Independent Adjudication Committee and blinded readings of Xe-133 and Technegas Ventilation and Tc-99m MAA Perfusion images were required for primary and secondary outcome data. Due to trial termination PE adjudication and blinded readings of images were not done.
Secondary
Negative Predictive Value (NPV) of Imaging for Diagnosis of PE
NPV of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first.
Time frame: Prospective, 30 days follow-up
Population: PE adjudication for final clinical diagnosis was to be determined by an Independent Adjudication Committee and blinded readings of Xe-133 and Technegas Ventilation and Tc-99m MAA Perfusion images were required for primary and secondary outcome data. Due to trial termination PE adjudication and blinded readings of images were not done.
Secondary
Positive Predictive Value (PPV) of Imaging for Diagnosis of PE
PPV of V/Q imaging for diagnosis of PE is determined by the results of blind-read assessment of images compared with truth using a subject's final clinical diagnosis following 30-day follow-up of occurence of PE or death, whichever occurs first.
Time frame: Prospective, 30 days follow-up
Population: PE adjudication for final clinical diagnosis was to be determined by an Independent Adjudication Committee and blinded readings of Xe-133 and Technegas Ventilation and Tc-99m MAA Perfusion images were required for primary and secondary outcome data. Due to trial termination PE adjudication and blinded readings of images were not done.
Secondary
Safety of Technegas in Patients With Possible PE
Safety will be assessed by the incidence of treatment emergence adverse events and changes in clinical laboratory measurements, blood pressure, oxygen saturation, physical examination and pulmonary examination before and after treatment.
Time frame: Prospective, from enrollment through 30 days follow-up
Population: All subjects who received Technegas and completed safety follow-up procedures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Safety of Technegas in Patients With Possible PE | Serious adverse events | 0 participants |
| Overall Study | Safety of Technegas in Patients With Possible PE | Other (not including serious) adverse events | 1 participants |