Pulmonary Surgical Procedures
Conditions
Brief summary
This study compares the equivalence of hyperpolarized 129Xe MRI as compared to 133Xe scintigraphy for the evaluation of pulmonary function in patients being evaluated for lung resection.
Detailed description
This is a multicenter, randomized, open-label, cross-over Phase 3 study evaluating hyperpolarized 129Xe gas MRI as compared to 133Xe scintigraphy for the evaluation of pulmonary function. This study will enroll subjects being evaluated for possible lung resection surgery (i.e. segmentectomy, lobectomy, or pneumonectomy). Subjects will have both a 129Xe MRI and 133Xe scintigraphy image. The vast differences in technique for obtaining hyperpolarized 129Xe MRI as compared to 133Xe scintigraphy make it impossible to blind study procedures. However, all image interpretation will be performed by personnel blinded to the subject's medical history and all study assessments.
Interventions
DRUG129Xe MRI
Evaluation of pulmonary function
DRUG133 Xe scintigraphy
Evaluation of pulmonary function
Sponsors
Polarean, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Open label crossover study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects ≥18 years of age. 2. Subject is being evaluated for possible lung resection (e.g., segmentectomy, lobectomy, or pneumonectomy). 3. Subject is able to undergo MRI imaging and able to fit in the MRI coil. 4. Subject is willing and able to comply with all study procedures. 5. Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study specific assessments or procedures.
Exclusion criteria
1. Baseline blood oxygen saturation (SpO2) \<90% at rest. For patients requiring routine supplemental oxygen, SpO2 measurements should be taken with the patient's normal oxygen supplementation. 2. Female subjects of childbearing potential with a positive serum pregnancy test at screening, or who are not taking (or not willing to take) acceptable birth control measures through the Follow-up Period. Adequate birth control methods include with a monogamous partner who was sterilized more than 6 months prior to screening, or measures with a Pearl index of \<1 used consistently and correctly (including intrauterine devices, or implantable, injectable, oral, or transdermal contraceptives). Women are not considered to be of childbearing potential if they meet at least 1 of the following 2 criteria as documented by the Investigator: * They have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at a minimum of 1 menstrual cycle prior to signing the ICF; or * They are post-menopausal: for women ≥55 years of age, defined as ≥1 year since their last menstrual period, or for women \<55 years of age, defined as ≥1 year since their last menstrual period and have a follicle-stimulating hormone (FSH) level in the laboratory's normal range for post-menopausal phase. 3. Women who are lactating and insist on breast feeding. 4. Subjects who have received any other investigational therapy within 4 weeks prior to Screening. 5. Subjects who require anesthesia or heavy sedation to undergo MRI testing. Mild sedation could be acceptable (i.e. a low dose oral acting anxiolytic medication such as alprazolam) as long as, in the opinion of the investigator, the subject meets Inclusion Criteria #4 and #5.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Predicted Percentage of Remaining Pulmonary Function | 48 hours | Predicted percentage of remaining pulmonary function is a pre-specified section of lung were to be removed. Investigators indicated which portions of lung were likely to be resected. Remaining percentage of pulmonary function was determined by subtracting the percentage of pulmonary function contributed by the planned zone of resection from the total pulmonary function using a standard 6-zone image analysis of the lung. The difference between predicted percentage of remaining pulmonary function was calculated by subtracting the value derived from the 133Xe scintigraphy image from the value derived from the 129Xe MRI image (e.g. 129Xe - 133Xe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measured Percentage of Total Ventilation Contributed by the Lower Left Lung Zone. | 48 hours | The fraction of total ventilation contributed by the lower left lung zone on 6-zone analysis. |
| Measured Percentage of Total Ventilation Contributed by the Upper Left Lung Zone. | 48 hours | The fraction of total ventilation contributed by the upper left lung zone on 6-zone analysis. |
| Measured Percentage of Total Ventilation Contributed by the Middle Left Lung Zone. | 48 hours | The fraction of total ventilation contributed by the middle left lung zone on 6-zone analysis. |
| Predicted Versus Measured FEV1 | 3 months | The difference between the scan-predicted post-operative FEV1 and the measured post-operative FEV1 |
| Measured Percentage of Total Ventilation Contributed by the Middle Right Lung Zone. | 48 hours | The fraction of total ventilation contributed by the middle right lung zone on 6-zone analysis. |
| Measured Percentage of Total Ventilation Contributed by the Lower Right Lung Zone. | 48 hours | The fraction of total ventilation contributed by the lower right lung zone on 6-zone analysis. |
| Measured Percentage of Total Ventilation Contributed by the Upper Right Lung Zone. | 48 hours | The fraction of total ventilation contributed by the upper right lung zone on 6-zone analysis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 129Xe Before 133Xe Subjects will undergo hyperpolarized 129Xe MRI first, followed by 133Xe scintigraphy
129Xe MRI: Evaluation of pulmonary function
133 Xe scintigraphy: Evaluation of pulmonary function | 14 |
| 133Xe Before 129Xe Subjects will undergo 133Xe scintigraphy first, followed by hyperpolarized 129Xe MRI
129Xe MRI: Evaluation of pulmonary function
133 Xe scintigraphy: Evaluation of pulmonary function | 20 |
| Total | 34 |
Baseline characteristics
| Characteristic | 129Xe Before 133Xe | Total | 133Xe Before 129Xe |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 11.5 | 62.2 years STANDARD_DEVIATION 9.7 | 64.9 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 34 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 27 Participants | 15 Participants |
| Region of Enrollment United States | 14 participants | 34 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 9 Participants | 23 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 20 |
| other Total, other adverse events | 2 / 14 | 3 / 20 |
| serious Total, serious adverse events | 1 / 14 | 0 / 20 |
Outcome results
Primary
Predicted Percentage of Remaining Pulmonary Function
Predicted percentage of remaining pulmonary function is a pre-specified section of lung were to be removed. Investigators indicated which portions of lung were likely to be resected. Remaining percentage of pulmonary function was determined by subtracting the percentage of pulmonary function contributed by the planned zone of resection from the total pulmonary function using a standard 6-zone image analysis of the lung. The difference between predicted percentage of remaining pulmonary function was calculated by subtracting the value derived from the 133Xe scintigraphy image from the value derived from the 129Xe MRI image (e.g. 129Xe - 133Xe).
Time frame: 48 hours
Population: The Efficacy Analysis Set is the group of subjects who had both a 129Xe MRI scan and a 133Xe scintigraphy scan, and for whom both scans met quality control criteria for analysis (as defined in the Independent Review Charter).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Predicted Percentage of Remaining Pulmonary Function | 73.4 percentage of remaining function | Standard Deviation 13 |
| 133Xe | Predicted Percentage of Remaining Pulmonary Function | 71.9 percentage of remaining function | Standard Deviation 12.1 |
Comparison: The primary efficacy analysis tested the mean difference in the predicted percentage of remaining pulmonary function as measured by 129Xe MRI relative to the value as measured by 133Xe scintigraphy (reference standard) if a pre-defined section of lung were resected.95% CI: [-0.75, 3.6]
Secondary
Measured Percentage of Total Ventilation Contributed by the Lower Left Lung Zone.
The fraction of total ventilation contributed by the lower left lung zone on 6-zone analysis.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Measured Percentage of Total Ventilation Contributed by the Lower Left Lung Zone. | 16.08 percentage of total function | Standard Deviation 4.43 |
| 133Xe | Measured Percentage of Total Ventilation Contributed by the Lower Left Lung Zone. | 12.37 percentage of total function | Standard Deviation 3.6 |
95% CI: [2.12, 5.29]
Secondary
Measured Percentage of Total Ventilation Contributed by the Lower Right Lung Zone.
The fraction of total ventilation contributed by the lower right lung zone on 6-zone analysis.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Measured Percentage of Total Ventilation Contributed by the Lower Right Lung Zone. | 16.39 percentage of total function | Standard Deviation 4.18 |
| 133Xe | Measured Percentage of Total Ventilation Contributed by the Lower Right Lung Zone. | 18.16 percentage of total function | Standard Deviation 3.62 |
95% CI: [-3.192, -0.335]
Secondary
Measured Percentage of Total Ventilation Contributed by the Middle Left Lung Zone.
The fraction of total ventilation contributed by the middle left lung zone on 6-zone analysis.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Measured Percentage of Total Ventilation Contributed by the Middle Left Lung Zone. | 22.27 percentage of total function | Standard Deviation 3.71 |
| 133Xe | Measured Percentage of Total Ventilation Contributed by the Middle Left Lung Zone. | 20.92 percentage of total function | Standard Deviation 2.88 |
95% CI: [0.184, 2.505]
Secondary
Measured Percentage of Total Ventilation Contributed by the Middle Right Lung Zone.
The fraction of total ventilation contributed by the middle right lung zone on 6-zone analysis.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Measured Percentage of Total Ventilation Contributed by the Middle Right Lung Zone. | 23.44 percentage of total function | Standard Deviation 3.07 |
| 133Xe | Measured Percentage of Total Ventilation Contributed by the Middle Right Lung Zone. | 26.16 percentage of total function | Standard Deviation 3.8 |
95% CI: [-4.096, -1.345]
Secondary
Measured Percentage of Total Ventilation Contributed by the Upper Left Lung Zone.
The fraction of total ventilation contributed by the upper left lung zone on 6-zone analysis.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Measured Percentage of Total Ventilation Contributed by the Upper Left Lung Zone. | 10.67 percentage of total function | Standard Deviation 2.11 |
| 133Xe | Measured Percentage of Total Ventilation Contributed by the Upper Left Lung Zone. | 10.28 percentage of total function | Standard Deviation 2.72 |
95% CI: [-0.476, 1.26]
Secondary
Measured Percentage of Total Ventilation Contributed by the Upper Right Lung Zone.
The fraction of total ventilation contributed by the upper right lung zone on 6-zone analysis.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Measured Percentage of Total Ventilation Contributed by the Upper Right Lung Zone. | 11.16 percentage of total function | Standard Deviation 2.97 |
| 133Xe | Measured Percentage of Total Ventilation Contributed by the Upper Right Lung Zone. | 12.12 percentage of total function | Standard Deviation 2.56 |
95% CI: [-2.101, 0.181]
Secondary
Predicted Versus Measured FEV1
The difference between the scan-predicted post-operative FEV1 and the measured post-operative FEV1
Time frame: 3 months
Population: This analysis set of all subjects that met the criteria for inclusion in the efficacy analysis set and had a post-operative FEV1 (spirometry) value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 129Xe MRI | Predicted Versus Measured FEV1 | -0.65 liters | Standard Deviation 0.6 |
| 133Xe | Predicted Versus Measured FEV1 | -0.65 liters | Standard Deviation 0.66 |