Lung Diseases
Conditions
Keywords
lung, cryoprobe, bronchoscopic, biopsy
Brief summary
The purpose of this study is to evaluate the safety and collect data on the initial effectiveness of a 1.1mm flexible single-use cryoprobe with oversheath used for transbronchial lung biopsy via a bronchoscopic approach.
Detailed description
A smaller (1.1mm), flexible, single-use cryoprobe with an oversheath has been developed that can be used for transbronchial biopsies. This device has the potential to gather larger and higher quality tissue samples than the standard method using forceps, and with potentially fewer complications than older, larger versions of the cryoprobe. This study does not involve randomization or assigning different patients to different procedures to compare. Everyone who enrolls in this study will undergo a standard of care bronchoscopy with a transbronchial biopsy using the 1.1mm sheath cryoprobe. The only difference from the standard of care approach is that the physician performing the transbronchial biopsy will use the 1.1mm sheath cryoprobe rather than forceps or another currently available larger cryoprobe. Patients enrolled in this study will have data collected by research staff for up to 30 days after the bronchoscopic biopsy procedure is performed. This 30-day follow-up period is the standard of care following bronchoscopic biopsy procedures.
Interventions
ERBE 1.1mm flexible single-use cryoprobe with oversheath
Sponsors
Erbe USA Incorporated
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a multi-center, non-randomized, single-arm, prospective trial. Therefore, all participants will have their transbronchial biopsy with the 1.1mm sheath cryoprobe rather than forceps or another currently available larger cryoprobe.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or Female, ≥ 18-years-old * Scheduled to undergo bronchoscopy with transbronchial biopsy as the standard medical care determined by their treating pulmonologist
Exclusion criteria
* Pregnant or nursing females, or females of child bearing potential who refuse to take a pregnancy test prior to enrollment * Individuals with current or recent systematic conditions, such as uncontrolled hypertension (systolic \> 200 mmHg or diastolic \> 110 mmHg), type 1 diabetes, severe pulmonary hypertension, acute kidney injury, stroke (within the last 6 months) or myocardial infarction (within the last 3 months) * Presence of bleeding disorder * Platelet count \<50,000 * Current use of systemic anticoagulation or antiplatelet therapy without the ability to hold therapy for the recommended amount of time prior to an invasive procedure (aspirin monotherapy is acceptable) * International Normalized Ratio (INR) \<1.5 * Robotic Bronchoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | Within 30 days of procedure | The number of participants enrolled who experienced a device related Serious Adverse Events (SAEs). SAEs include Grade 3-4 bleeding (bleeding causing cardiopulmonary instability or requiring inflation of a bronchial blocker), pneumothorax requiring chest tube placement (Grade 2+), or 30-day respiratory failure and death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Histologic Accessibility Grade | Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour) | Grade 0: Does not contain alveolar structures and can therefore not be assessed Grade 1: Very poor specimen quality; not possible to assess the relevant morphologic and histologic features Grade 2: Poor specimen quality; assessment of relevant morphologic and histologic structures and features is severely compromised and not possible Grade 3: High limitations in specimen quality; assessment is severely compromised but limited evaluation is possible Grade 4: Moderate limitations in specimen quality; assessment is moderately compromised but evaluation is possible Grade 5: Low limitations in specimen quality; assessment is somewhat compromised but possible Grade 6: The specimen allows for complete and unrestricted assessment of all relevant morphologic and histologic structures and features |
| Diagnostic Yield as Assessed by Number of Patients for Which Cryobiopsy Led to a Diagnosis | During procedure, up to 1 hour | Diagnostic yield is defined as number of patients for which cryobiopsy led to a diagnosis. Diagnostic yield will be determined from the results of cryobiopsy specimen only. A biopsy that results in a specific diagnosis, either malignant or benign (granuloma, inflammation, fibrosis, infection) will be assumed to be a true positive. Atypia, minimal inflammation or lung parenchyma without pathologic findings on final pathology reads are considered non-diagnostic. |
| Total Histologic Area (Square Millimeters) | Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour) | Amount of total histologic tissue in square millimeters observed under microscope. |
| Alveolated Area (Square Millimeters) | Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour) | Total amount of area in square millimeters containing alveoli. |
| Number of Participants With Minor Adverse Events | Within 30 days of procedure | The number of participants enrolled who experienced a device related Minor Adverse Event (AE). AEs include Grade 1-2 bleeding (bleeding requiring suction to clear or wedging of the biopsied segment with the flexible bronchoscope and/or iced saline), or pneumothorax not requiring chest tube placement (Grade 1). |
| Percent Crush Artifact | Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour) | Percent of tissue distortion resulting from even the minimal compression of the tissue, which may rearrange tissue morphology. |
| Artifact Free Lung Parenchyma Percent | Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour) | Percent of the lung parenchyma (alveoli, alveolar ducts and respiratory bronchioles) without artifact. |
| Activation Time (Seconds) | At the time of procedure, up to 1 hour | Time of activation of cryoprobe. |
| Procedure Time | At the time of procedure, up to 1 hour | Time for entire procedure measured in minutes. |
| Open Alveoli Percent | Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour) | Percentage of all alveoli that are open. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm: Cryoprobe Everyone who enrolls in this study will undergo a standard of care bronchoscopy with a transbronchial biopsy using the 1.1mm sheath cryoprobe.
ERBECRYO® 2 Cryosurgical Unit and Accessories - K190651: ERBE 1.1mm flexible single-use cryoprobe with oversheath | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Single Arm: Cryoprobe |
|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 14 |
| Body Mass Index (BMI) | 26 kg/m^2 STANDARD_DEVIATION 7 |
| Bronchial Blocker Used | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Indication for Biopsy Diffuse Lung Disease | 22 Participants |
| Indication for Biopsy Lung Transplant | 25 Participants |
| Indication for Biopsy Pulmonary Parenchymal Lesion | 3 Participants |
| Location of Biopsy Left Lower Lobe | 12 Participants |
| Location of Biopsy Left Upper Lobe | 3 Participants |
| Location of Biopsy Right Lower Lobe | 31 Participants |
| Location of Biopsy Right Middle Lobe | 2 Participants |
| Location of Biopsy Right Upper Lobe | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 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 | 36 Participants |
| Region of Enrollment United States | 50 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 19 Participants |
| Smoking Status Current | 2 Participants |
| Smoking Status Former | 20 Participants |
| Smoking Status Never | 28 Participants |
| Type of Airway Endotracheal Tube | 21 Participants |
| Type of Airway Laryngeal Mask Airway | 19 Participants |
| Type of Airway Rigid Bronchoscopy | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 50 |
| other Total, other adverse events | 22 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Number of Participants With Serious Adverse Events
The number of participants enrolled who experienced a device related Serious Adverse Events (SAEs). SAEs include Grade 3-4 bleeding (bleeding causing cardiopulmonary instability or requiring inflation of a bronchial blocker), pneumothorax requiring chest tube placement (Grade 2+), or 30-day respiratory failure and death.
Time frame: Within 30 days of procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm: Cryoprobe | Number of Participants With Serious Adverse Events | 0 Participants |
Secondary
Activation Time (Seconds)
Time of activation of cryoprobe.
Time frame: At the time of procedure, up to 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm: Cryoprobe | Activation Time (Seconds) | 4.2 seconds |
Secondary
Alveolated Area (Square Millimeters)
Total amount of area in square millimeters containing alveoli.
Time frame: Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Single Arm: Cryoprobe | Alveolated Area (Square Millimeters) | Per Piece | 2.47 square millimeters |
| Single Arm: Cryoprobe | Alveolated Area (Square Millimeters) | Per Patient | 11.39 square millimeters |
Secondary
Artifact Free Lung Parenchyma Percent
Percent of the lung parenchyma (alveoli, alveolar ducts and respiratory bronchioles) without artifact.
Time frame: Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm: Cryoprobe | Artifact Free Lung Parenchyma Percent | 90.86 percent |
Secondary
Diagnostic Yield as Assessed by Number of Patients for Which Cryobiopsy Led to a Diagnosis
Diagnostic yield is defined as number of patients for which cryobiopsy led to a diagnosis. Diagnostic yield will be determined from the results of cryobiopsy specimen only. A biopsy that results in a specific diagnosis, either malignant or benign (granuloma, inflammation, fibrosis, infection) will be assumed to be a true positive. Atypia, minimal inflammation or lung parenchyma without pathologic findings on final pathology reads are considered non-diagnostic.
Time frame: During procedure, up to 1 hour
Population: The analysis was broken down by type of cryobiopsy indication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm: Cryoprobe | Diagnostic Yield as Assessed by Number of Patients for Which Cryobiopsy Led to a Diagnosis | Lung Transplant | 23 Participants |
| Single Arm: Cryoprobe | Diagnostic Yield as Assessed by Number of Patients for Which Cryobiopsy Led to a Diagnosis | Diffuse Lung Disease | 16 Participants |
| Single Arm: Cryoprobe | Diagnostic Yield as Assessed by Number of Patients for Which Cryobiopsy Led to a Diagnosis | Pulmonary Parenchymal Lesion | 1 Participants |
Secondary
Mean Histologic Accessibility Grade
Grade 0: Does not contain alveolar structures and can therefore not be assessed Grade 1: Very poor specimen quality; not possible to assess the relevant morphologic and histologic features Grade 2: Poor specimen quality; assessment of relevant morphologic and histologic structures and features is severely compromised and not possible Grade 3: High limitations in specimen quality; assessment is severely compromised but limited evaluation is possible Grade 4: Moderate limitations in specimen quality; assessment is moderately compromised but evaluation is possible Grade 5: Low limitations in specimen quality; assessment is somewhat compromised but possible Grade 6: The specimen allows for complete and unrestricted assessment of all relevant morphologic and histologic structures and features
Time frame: Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm: Cryoprobe | Mean Histologic Accessibility Grade | 4.9 score on a scale | Standard Deviation 1.3 |
Secondary
Number of Participants With Minor Adverse Events
The number of participants enrolled who experienced a device related Minor Adverse Event (AE). AEs include Grade 1-2 bleeding (bleeding requiring suction to clear or wedging of the biopsied segment with the flexible bronchoscope and/or iced saline), or pneumothorax not requiring chest tube placement (Grade 1).
Time frame: Within 30 days of procedure
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm: Cryoprobe | Number of Participants With Minor Adverse Events | Grade 1 Pneumothorax | 2 Participants |
| Single Arm: Cryoprobe | Number of Participants With Minor Adverse Events | Grade 1-2 Bleeding | 25 Participants |
Secondary
Open Alveoli Percent
Percentage of all alveoli that are open.
Time frame: Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm: Cryoprobe | Open Alveoli Percent | 66.48 percent |
Secondary
Percent Crush Artifact
Percent of tissue distortion resulting from even the minimal compression of the tissue, which may rearrange tissue morphology.
Time frame: Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm: Cryoprobe | Percent Crush Artifact | 0.5 percent |
Secondary
Procedure Time
Time for entire procedure measured in minutes.
Time frame: At the time of procedure, up to 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm: Cryoprobe | Procedure Time | 22 minutes |
Secondary
Total Histologic Area (Square Millimeters)
Amount of total histologic tissue in square millimeters observed under microscope.
Time frame: Data assessed at the time of review of biopsy sample (up to one year post index procedure) and participants were assessed for the outcome measure at the time of biopsy procedure (up to 1 hour)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm: Cryoprobe | Total Histologic Area (Square Millimeters) | 54.4 square millimeters |