Transbronchial Lung CryobiopsyNCT04285463
Defining Optimal Settings for Transbronchial Lung Cryobiopsy II: An Ex-Vivo Human Lungs Model Study for Improvement of Specimen Quality
A study testing Transbronchial Lung Cryobiopsy (TBLC) in people with Transbronchial Lung Cryobiopsy, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial summary
Diffuse parenchymal lung disease (DPLD) or Interstitial Lung Disease (ILD) comprises a broad variety of lung pathologies in which accurate diagnosis is crucial given to the different prognosis and therapeutic approaches, especially with the advent of new antifibrotic therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transbronchial Lung Cryobiopsy
- What is being tested?
- Transbronchial Lung Cryobiopsy (TBLC)
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- 4 Mar 2020to 17 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Lungs from patients undergoing lung transplantation after their removal from the recipient patient with previous informed consent signed before transplantation.
Who cannot join
- Patients not candidates for surgical removal of the lungs during the act of transplantation.
Trial locations and contacts
1 site in 1 country.
About this study
Diffuse parenchymal lung disease (DPLD) or Interstitial Lung Disease (ILD) comprises a broad variety of lung pathologies in which accurate diagnosis is crucial given to the different prognosis and therapeutic approaches, especially with the advent of new antifibrotic therapies.
Histology is an important tool when radiologic findings, clinical manifestations and bronchoalveolar lavage analysis are inconclusive. Surgical lung biopsy (SLB) is the gold standard for tissue sampling/analysis, however there is an associated cost and risk with a mortality-related between 1.8 and 3.6% for elective cases and up to 16% for the non-elective ones.
Read more
Transbronchial lung cryobiopsy (TBLC) is a safe, well-established technique used to obtain lung biopsies with large, high-quality specimens using compressed gas to freeze the tissue. The larger fragments do not contain the same crush artifacts seen in conventional transbronchial biopsies (TBB), but the non-standardization of the technique could be a limitation to the quality of the specimens and its safety.
The objective of this project is to determine the optimal settings for TBLC in human lungs with ILD in order to obtain the best quality specimens with the lowest risk profile. Two previous studies using animal models evaluated the technical components, such as probe size, freezing time and probe to pleura distance that results in good quality specimens. However, these were in normal animal lungs without ILD. In this new project, multiple TBLCs will be taken from lungs of documented ILD patients undergoing lung transplantation after their removal from the recipient patient at the time of lung transplantation.
Read the detailed description
Transbronchial lung cryobiopsy (TBLC) is a less invasive procedure than surgical lung biopsy (SLB) to establish the diagnosis of interstitial lung disease (ILD) and as an endoscopic intervention can be done as an outpatient procedure. This technology has also being used for cryoadhesion to remove tissue from the airway. The freeze lung tissue provides bigger samples than the conventional transbronchial lung biopsy (TBB), less crush artifacts with more alveolar structures which gives better quality specimens and diagnostic yield for ILDs that usually has a complex morphologic pattern like unusual interstitial pneumonia and nonspecific interstitial pneumonia compared by TBB forceps biopsy. A recent trial showed that the histological diagnosis was obtained in only 34.1% of patients who had a TBB and the diagnostic yield of this technique was 29.1%. Lung cryobiopsy is associated with higher diagnostic yield (up to 83%) than TBBs and because of this, TBB is not recommended for ILD diagnosis in the current guidelines.
The diagnostic algorithm for ILD etiology definition is complex and has been born out of the necessity for diagnosis in patients where gold standard lung biopsy is associated with significant risk and therefore is typically saved as a last resort. Currently, SLB is indicated in only about 4 to 5% of the new cases suspected to have ILD. If TBLC is shown to be associated with lower complication rates, the investigator may be able to obtain definitive histological diagnoses in a great majority of cases and forego complex, inefficient and inaccurate methods of disease diagnosis. However, in order to replace SLB, TBLC should provide a similar diagnostic yield and better safety profile. Compared to SLB, retrospective data has shown that TBLC is associated with fewer complications, lower mortality, and better patient tolerance and recently one multicentric prospective trial (COLDICE) was designed to compare both techniques and guide the diagnostic accuracy for TBLC, not yet known. Several groups have published retrospective series of TBLC in ILD with promising results and diagnostic yields, however, the different technical components for performing a TBLC are very heterogeneous among the published series. Probe size, freezing time and distance from the probe to pleura are all parameters that may influence the size and quality of the samples.
As a technique recently applied to obtain adequate lung tissue for ILD differential diagnosis, its use was first described in 2009, there is no standard way to perform TBLC, and very limited data on how these parameters can influence biopsy quality. It is not clear which settings or parameters could affect the results. A few animal studies documented positive correlation between freezing time and biopsy size in TBLC. Published series on humans have used 4 and 6 seconds with a mini-cryoprobe probe and between 1 to 2 cm from the visceral pleura.
One of the limitations from the previous studies was that the lung specimens were obtained from healthy animal lungs. The lungs from patients undergoing transplant are affected by diffuse parenchymal pathologies and should offer a good predictor of how to obtain the best specimens for highest diagnostic yield in human lungs. The ex-vivo human model also has the advantage of performing multiple lung biopsies without any risks related with the procedure in in-vivo patients.
- Conditions
- Transbronchial Lung Cryobiopsy
- Being tested
- Transbronchial Lung Cryobiopsy (TBLC)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transbronchial Lung Cryobiopsy (TBLC)Diagnostic test
TBLC is a relatively new endoscopic technique used to obtain lung parenchyma specimens. It is a minimally invasive technique performed with a flexible or rigid bronchoscope under deep sedation or general anesthesia. Flexible cryoprobes of either 1.9 or 2.4 mm in diameter are introduced into a bronchoscope and a compressed gas, most commonly carbon dioxide or nitrous oxide, is released at high flow at the tip of the probe. As the tissue rapidly freezes, it adheres to the probe and is avulsed and extracted with a quick pullback movement followed by immediate extraction of samples.
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the probe size that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model.
Multiple Transbronchial Lung Cryobiopsies (TBLCs) will be taken from the lungs using different probe sizes: 1.9 and 2.4 milimeters .
The size and quality of the lung tissue samples will be compared to analyze which settings are optimal for obtaining the best quality specimens.
Measured: Time of procedure
Determine the freezing probe time that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model.
Multiple Transbronchial Lung Cryobiopsies (TBLCs) will be taken from the lungs and during the procedure each probe (1.9 and 2.4 milimiters) will be activated with different freezing times: first with 30 seconds followed by 20 seconds, then 10 seconds, 5 seconds and 3 seconds, successively.
The size and quality of the lung tissue samples will be compared to analyze which settings are optimal for obtaining the best quality specimens.
Measured: Time of procedure
Determine the distance from tip of the probe to the pleura that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model.
Multiple Transbronchial Lung Cryobiopsies (TBLCs) will be taken from the lungs and during the procedure each probe (1.9 and 2.4 milimiters) will be activated at different distances from the pleura Inside the bronchus: first 5 milimeters apart, then 10 milimeters and 20 milimeters, successively.
Measured: Time of procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study start4 Mar 2020
- Primary completion17 Jul 2021
- Study completion17 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transbronchial Lung CryobiopsyStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Moishe Liberman, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04285463
- Sponsor's protocol ID
- 19.280
- Status last verified
- Mar 2023
- First submitted
- 19 Feb 2020
- Last updated
- 27 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Optimal Settings for Transbronchial Lung Cryobiopsy II: An Ex-Vivo Human Lungs Model Study for Improvement of Specimen Quality
- ClinicalTrials.gov ID
- NCT04285463
- Acronym / sponsor ID
- 19.280
- Conditions
- Transbronchial Lung Cryobiopsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Study start
- 4 Mar 2020 (actual)
- Primary completion
- 17 Jul 2021 (actual)
- Study completion
- 17 Jul 2021 (actual)
- First posted
- 26 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diffuse parenchymal lung disease (DPLD) or Interstitial Lung Disease (ILD) comprises a broad variety of lung pathologies in which accurate diagnosis is crucial given to the different prognosis and therapeutic approaches, especially with the advent of new antifibrotic therapies.
Histology is an important tool when radiologic findings, clinical manifestations and bronchoalveolar lavage analysis are inconclusive. Surgical lung biopsy (SLB) is the gold standard for tissue sampling/analysis, however there is an associated cost and risk with a mortality-related between 1.8 and 3.6% for elective cases and up to 16% for the non-elective ones.
Transbronchial lung cryobiopsy (TBLC) is a safe, well-established technique used to obtain lung biopsies with large, high-quality specimens using compressed gas to freeze the tissue. The larger fragments do not contain the same crush artifacts seen in conventional transbronchial biopsies (TBB), but the non-standardization of the technique could be a limitation to the quality of the specimens and its safety.
The objective of this project is to determine the optimal settings for TBLC in human lungs with ILD in order to obtain the best quality specimens with the lowest risk profile. Two previous studies using animal models evaluated the technical components, such as probe size, freezing time and probe to pleura distance that results in good quality specimens. However, these were in normal animal lungs without ILD. In this new project, multiple TBLCs will be taken from lungs of documented ILD patients undergoing lung transplantation after their removal from the recipient patient at the time of lung transplantation.
Detailed description
Transbronchial lung cryobiopsy (TBLC) is a less invasive procedure than surgical lung biopsy (SLB) to establish the diagnosis of interstitial lung disease (ILD) and as an endoscopic intervention can be done as an outpatient procedure. This technology has also being used for cryoadhesion to remove tissue from the airway. The freeze lung tissue provides bigger samples than the conventional transbronchial lung biopsy (TBB), less crush artifacts with more alveolar structures which gives better quality specimens and diagnostic yield for ILDs that usually has a complex morphologic pattern like unusual interstitial pneumonia and nonspecific interstitial pneumonia compared by TBB forceps biopsy. A recent trial showed that the histological diagnosis was obtained in only 34.1% of patients who had a TBB and the diagnostic yield of this technique was 29.1%. Lung cryobiopsy is associated with higher diagnostic yield (up to 83%) than TBBs and because of this, TBB is not recommended for ILD diagnosis in the current guidelines.
The diagnostic algorithm for ILD etiology definition is complex and has been born out of the necessity for diagnosis in patients where gold standard lung biopsy is associated with significant risk and therefore is typically saved as a last resort. Currently, SLB is indicated in only about 4 to 5% of the new cases suspected to have ILD. If TBLC is shown to be associated with lower complication rates, the investigator may be able to obtain definitive histological diagnoses in a great majority of cases and forego complex, inefficient and inaccurate methods of disease diagnosis. However, in order to replace SLB, TBLC should provide a similar diagnostic yield and better safety profile. Compared to SLB, retrospective data has shown that TBLC is associated with fewer complications, lower mortality, and better patient tolerance and recently one multicentric prospective trial (COLDICE) was designed to compare both techniques and guide the diagnostic accuracy for TBLC, not yet known. Several groups have published retrospective series of TBLC in ILD with promising results and diagnostic yields, however, the different technical components for performing a TBLC are very heterogeneous among the published series. Probe size, freezing time and distance from the probe to pleura are all parameters that may influence the size and quality of the samples.
As a technique recently applied to obtain adequate lung tissue for ILD differential diagnosis, its use was first described in 2009, there is no standard way to perform TBLC, and very limited data on how these parameters can influence biopsy quality. It is not clear which settings or parameters could affect the results. A few animal studies documented positive correlation between freezing time and biopsy size in TBLC. Published series on humans have used 4 and 6 seconds with a mini-cryoprobe probe and between 1 to 2 cm from the visceral pleura.
One of the limitations from the previous studies was that the lung specimens were obtained from healthy animal lungs. The lungs from patients undergoing transplant are affected by diffuse parenchymal pathologies and should offer a good predictor of how to obtain the best specimens for highest diagnostic yield in human lungs. The ex-vivo human model also has the advantage of performing multiple lung biopsies without any risks related with the procedure in in-vivo patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Lungs from patients undergoing lung transplantation after their removal from the recipient patient with previous informed consent signed before transplantation.
Key exclusion criteria (1 listed)
- Patients not candidates for surgical removal of the lungs during the act of transplantation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transbronchial Lung Cryobiopsy (TBLC)TBLC is a relatively new endoscopic technique used to obtain lung parenchyma specimens. It is a minimally invasive technique performed with a flexible or rigid bronchoscope under deep sedation or general anesthesia. Flexible cryoprobes of either 1.9 or 2.4 mm in diameter are introduced into a bronchoscope and a compressed gas, most commonly carbon dioxide or nitrous oxide, is released at high flow at the tip of the probe. As the tissue rapidly freezes, it adheres to the probe and is avulsed and extracted with a quick pullback movement followed by immediate extraction of samples. | Diagnostic test | – |
Primary outcome
Determine the probe size that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model.
Time frame: Time of procedure
Multiple Transbronchial Lung Cryobiopsies (TBLCs) will be taken from the lungs using different probe sizes: 1.9 and 2.4 milimeters . The size and quality of the lung tissue samples will be compared to analyze which settings are optimal for obtaining the best quality specimens.
Determine the freezing probe time that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model.
Time frame: Time of procedure
Multiple Transbronchial Lung Cryobiopsies (TBLCs) will be taken from the lungs and during the procedure each probe (1.9 and 2.4 milimiters) will be activated with different freezing times: first with 30 seconds followed by 20 seconds, then 10 seconds, 5 seconds and 3 seconds, successively. The size and quality of the lung tissue samples will be compared to analyze which settings are optimal for obtaining the best quality specimens.
Determine the distance from tip of the probe to the pleura that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model.
Time frame: Time of procedure
Multiple Transbronchial Lung Cryobiopsies (TBLCs) will be taken from the lungs and during the procedure each probe (1.9 and 2.4 milimiters) will be activated at different distances from the pleura Inside the bronchus: first 5 milimeters apart, then 10 milimeters and 20 milimeters, successively.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transbronchial Lung Cryobiopsy (TBLC) in people with Transbronchial Lung Cryobiopsy, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the probe size that yield the best lung biopsy specimens for histological analysis in an ex-vivo human model. (time frame: Time of procedure). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.