Ignite Creation Date:
2024-05-06 @ 3:53 AM
Last Modification Date:
2024-10-26 @ 11:40 AM
Study NCT ID:
NCT02395939
Status:
UNKNOWN
Last Update Posted:
2015-10-12
First Post:
2015-03-08
Brief Title:
Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs CT Guided Biopsy for PPL
Sponsor:
Middlemore Hospital New Zealand
Organization:
Middlemore Hospital New Zealand
Study Overview
Official Title:
Randomised Controlled Trial Comparing the Diagnostic Yield of Radial Endo-Bronchial Ultra-Sound R-EBUS Guided Cryo-biopsy Vs CT-guided Transthoracic Biopsy in Patients With Parenchymal Lung Lesion Suspected of Lung Cancer CT-CROP
Status:
UNKNOWN
Status Verified Date:
2015-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CT-CROP
Brief Summary:
Obtaining a tissue sample to diagnose a PPL suspected of cancerous origin is of utmost importance The current gold standard Transthoracic CT guided needle biopsy approach with a success rate of 90 comes at the expense of an increased side effect profile
Given that most lung cancers originate in the bronchus hence named bronchogenic carcinoma it would be rational to think that endobronchial route should provide the best route of sampling with the least amount of side effects Radial EBUS has become popular during the last decade as an endobronchial modality in diagnosing PPL with minimal side effects However the yield is still not satisfactory in comparison to CT guided biopsy with only 73 success rate in a meta-analysis There is also with wide variation in different centres
Use of a new biopsy method called cryo-biopsy using the R-EBUS guide sheath may bridge the gap and increase the diagnostic yield of PPL
Cryo biopsy had been proven to give larger sample sizes and reduced crush artefact compared to the conventional radial EBUS biopsies
However there have been no head to head trials comparing Cryo-probe biopsy vs the gold standard CT guided biopsy
Cryo-biopsy has very favourable side effect profile without any pneumothorax occurrence If the yield were to be non-inferior to CT guided biopsy this would certainly be the preferred choice of biopsy for PPL in the future
Methodology All patients with a PPL requiring a diagnostic biopsy will be eligible for recruitment to the trial The recruited patients will be randomly allocated to either CT guided core biopsy or radial EBUS guided cryobiopsy
Study design Multi centre intervetionalrandomised control trial
Study population
Patients diagnosed with a PPL that requires a biopsy
If the patient is randomised to the cryo biopsy arm
The procedure will be done under the usual guidelines and practice of the centre as for a flexible bronchoscopy procedure
Once flexible bronchoscopy is introduced the pre-determined desired segment the R-EBUS is inserted covered by the GS
Once the R EBUS locates the lesion the GS is left in situ and the USS probe is retracted
The cryoprobe is then inserted through the GS to the desired location Flexible Cryoprobe outer diameter 19mm will be applied for 4 seconds for each biopsy The cryogen gas used will be Co2
The probe will be retracted together with the GS and the bronchoscope en masse after each biopsy A minimum of 1 and maximum of 3 samples will be taken
A CXR is taken within 1 hour post procedure to access for pneumothorax Adverse events during the procedure will be recorded If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively Minor bleeding will not be considered an additional cost as this occurs with routine bronchoscopy
If the patient is randomised to the CT biopsy arm
A CT guided core biopsy will be performed as per usual practice of that centre 2-6 passes will be performed for each PPL
A CXR 1hour post procedure will be performed to assess for pneumothorax or procedure related bleeding
If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively
At the pathology
All samples will be assessed for the size of the sample and the suitability for molecular testing An independent pathologist will assess samples
Economic analysis
For both procedures Both direct and indirect costs will be calculated The main aim of cost analysis is to calculate the cost of side effect management in each arm to determine the most cost-effective method of sampling a PPL
Given that most lung cancers originate in the bronchus hence named bronchogenic carcinoma it would be rational to think that endobronchial route should provide the best route of sampling with the least amount of side effects Radial EBUS has become popular during the last decade as an endobronchial modality in diagnosing PPL with minimal side effects However the yield is still not satisfactory in comparison to CT guided biopsy with only 73 success rate in a meta-analysis There is also with wide variation in different centres
Use of a new biopsy method called cryo-biopsy using the R-EBUS guide sheath may bridge the gap and increase the diagnostic yield of PPL
Cryo biopsy had been proven to give larger sample sizes and reduced crush artefact compared to the conventional radial EBUS biopsies
However there have been no head to head trials comparing Cryo-probe biopsy vs the gold standard CT guided biopsy
Cryo-biopsy has very favourable side effect profile without any pneumothorax occurrence If the yield were to be non-inferior to CT guided biopsy this would certainly be the preferred choice of biopsy for PPL in the future
Methodology All patients with a PPL requiring a diagnostic biopsy will be eligible for recruitment to the trial The recruited patients will be randomly allocated to either CT guided core biopsy or radial EBUS guided cryobiopsy
Study design Multi centre intervetionalrandomised control trial
Study population
Patients diagnosed with a PPL that requires a biopsy
If the patient is randomised to the cryo biopsy arm
The procedure will be done under the usual guidelines and practice of the centre as for a flexible bronchoscopy procedure
Once flexible bronchoscopy is introduced the pre-determined desired segment the R-EBUS is inserted covered by the GS
Once the R EBUS locates the lesion the GS is left in situ and the USS probe is retracted
The cryoprobe is then inserted through the GS to the desired location Flexible Cryoprobe outer diameter 19mm will be applied for 4 seconds for each biopsy The cryogen gas used will be Co2
The probe will be retracted together with the GS and the bronchoscope en masse after each biopsy A minimum of 1 and maximum of 3 samples will be taken
A CXR is taken within 1 hour post procedure to access for pneumothorax Adverse events during the procedure will be recorded If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively Minor bleeding will not be considered an additional cost as this occurs with routine bronchoscopy
If the patient is randomised to the CT biopsy arm
A CT guided core biopsy will be performed as per usual practice of that centre 2-6 passes will be performed for each PPL
A CXR 1hour post procedure will be performed to assess for pneumothorax or procedure related bleeding
If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively
At the pathology
All samples will be assessed for the size of the sample and the suitability for molecular testing An independent pathologist will assess samples
Economic analysis
For both procedures Both direct and indirect costs will be calculated The main aim of cost analysis is to calculate the cost of side effect management in each arm to determine the most cost-effective method of sampling a PPL
Detailed Description:
Obtaining a tissue sample to diagnose PPL suspected of cancerous origin is of utmost importance Sampling of PPL can be done either through the chest wall transthoracic or through the airways that lead to the PPL endobronchial
The current gold slandered is Transthoracic Needle Aspiration TTNA approach is done by using CT guided biopsy with a success rate of 90 However this success in diagnostic yield comes at the expense of increased side effect profile including a very high risk of pneumothorax up to 30 Half of these patients require chest drain insertion
Given that most lung cancers originate in the bronchus hence named bronchogenic carcinoma it would be rational to think that endobronchial route should provide the best way of sampling with least amount of side effects However the yield is still not satisfactory and has a wide confidence interval
When diagnosing a PPL endobronchially accurate visualisation of the lesion is the main issue To overcome this issue various navigation methods have been used to accurately locate the PPL to improve the diagnostic yield
The use of Radial Endo Bronchial USS R-EBUS is one such navigational modality The conventional R-EBUS guided biopsies are carried out using cytology brushes and forceps biopsy These methods had been extremely safe with 1 pneumothorax rate however the diagnostic yield in a meta-analysis of 14 studies is only 73
Use of a new biopsy method called cryo-biopsy may bridge the gap and increase the diagnostic yield of PPL
Cryotherapy is the use of a compressed gas released at a high flow that rapidly expands and creates very low temperatures up to -89C These very low temperatures then cause tissue to get stuck to the end of the cryo-probe Due to the rapid cooling the microvasculature around the biopsy site go into vasospasm and reduces bleeding despite a large biopsy sample being acquired
Cryotherapy has been used in the airway since 1968 The ability to use this method while the patient is using high flow oxygen as well as being a cheap equipment to use makes it very affordable and useful equipment in any interventional bronchoscopy unit Most bronchoscopists will be trained and familiar with cryo biopsy technique
The cryo-biopsies were compared against forceps biopsies in this study and demonstrated larger sample size and less crush artefact favouring cryo- biopsy use
The most encouraging results published recently was looking at cryo-biopsy for PPL using R-EBUS guidance which demonstrated a yield of 74 and the ability to obtain 3 times larger tissue biopsies when compared to traditional forceps biopsies There were no pneumothorax in this cohort and only minor bleeding was recorded requiring bronchoscopy suction alone and no other intervention recorded
However there had been no head to head trials comparing Cryo-probe vs the gold standard CT-guided biopsy
As cryo-biopsy has very favourable side effect profile without any pneumothorax occurrence if the yield were to be non-inferior this would certainly be the preferred choice of biopsy for PPL in the future
With regards to cost analysis it has been shown that R-EBUS guided biopsy Vs CT guided biopsy has similar cost profiles for the procedure alone However the final cost of the procedure depends on the side effects experienced using each procedure making CT guided biopsy the costlier of the 2 methods
However cryo-biopsy and CT guided biopsy had not been compared in an economic analysis before
Methodology All patients with a PPL requiring a diagnosis will be eligible for the trial
Prior to the procedure Either CT guided biopsy or cryo biopsy
1 The size of the lesion will be recorded volume assessment and maximum diameter on the axial scan from the CT scan prior to procedure
If the patient is randomised to the cryo biopsy arm
1 The bronchoscopist will plan the pathway to the PPL based on the CT scans The sub segments from which the lesions could be biopsied will be pre-determined and documented If available virtual bronchoscopy will be used to confirm this navigational path to the lesion
2 Maximum time allowed to locate the lesion via R-EBUS would be 20 mins
3 The procedure will be done under the usual guidelines and practice of the centre as for a flexible bronchoscopy procedure As this is a multi-centre trial centre variation on the usual practice of bronchoscopy may vary
4 Some centres may use fluoroscopy in addition to localise the lesion This is also acceptable in the protocol
5 If an endobronchial lesion is found then the patient is excluded
6 Once flexible bronchoscopy is introduced the pre-determined desired segment the R-EBUS is inserted covered by the GS
7 Once the R EBUS locates the lesion the GS is left in situ and the USS probe is retracted
8 The cryo probe is then inserted through the GS to the desired location Flexible Cryo probe outer diameter 19 mm will be applied for 4 seconds for each biopsy
9 The probe will be retracted together with the GS and the bronchoscope en masse after each biopsy
10 A minimum of 1 and maximum of 3 samples will be taken
11 A CXR is taken within 1-hour post procedure to access for pneumothorax
12 Adverse events during the procedure will be recorded as Minor bleeding requiring cold saline or adrenalin moderate bleeding requiring a bronchial blocker or APC and a large bleed requiring blood transfusion FFP cardiothoracic support etc
13 If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively Minor bleeding will not be considered an additional cost as this occurs with routine bronchoscopy
If the patient is randomised to the CT biopsy arm
1 The interventional radiologist will decide on the best position for the patient to stay during the procedure
2 A core biopsy will be performed as per usual practice of that centre In CMDHB all CT guided biopsies are performed as core biopsies
3 The patient will have 2-6 biopsies from the PPL
4 Patient lies on the side of the biopsy for 1 hour post procedure Post procedure monitoring will be performed as per usual practice
5 A CXR 1 hour post procedure will be performed to assess for pneumothorax or procedure related bleeding
6 If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively
At the pathology
All samples will be assessed for area of specimen to assess the size The ability to perform molecular typing will be documented
An independent pathologist will assess samples
Economic analysis
For both procedures Both direct costs From the hospital records and indirect cost by administering a patient questionnaire will be recorded
The main aim of cost analysis is to calculate the cost of side effect management in each arm to determine the most cost effective method of sampling a PPL
The current gold slandered is Transthoracic Needle Aspiration TTNA approach is done by using CT guided biopsy with a success rate of 90 However this success in diagnostic yield comes at the expense of increased side effect profile including a very high risk of pneumothorax up to 30 Half of these patients require chest drain insertion
Given that most lung cancers originate in the bronchus hence named bronchogenic carcinoma it would be rational to think that endobronchial route should provide the best way of sampling with least amount of side effects However the yield is still not satisfactory and has a wide confidence interval
When diagnosing a PPL endobronchially accurate visualisation of the lesion is the main issue To overcome this issue various navigation methods have been used to accurately locate the PPL to improve the diagnostic yield
The use of Radial Endo Bronchial USS R-EBUS is one such navigational modality The conventional R-EBUS guided biopsies are carried out using cytology brushes and forceps biopsy These methods had been extremely safe with 1 pneumothorax rate however the diagnostic yield in a meta-analysis of 14 studies is only 73
Use of a new biopsy method called cryo-biopsy may bridge the gap and increase the diagnostic yield of PPL
Cryotherapy is the use of a compressed gas released at a high flow that rapidly expands and creates very low temperatures up to -89C These very low temperatures then cause tissue to get stuck to the end of the cryo-probe Due to the rapid cooling the microvasculature around the biopsy site go into vasospasm and reduces bleeding despite a large biopsy sample being acquired
Cryotherapy has been used in the airway since 1968 The ability to use this method while the patient is using high flow oxygen as well as being a cheap equipment to use makes it very affordable and useful equipment in any interventional bronchoscopy unit Most bronchoscopists will be trained and familiar with cryo biopsy technique
The cryo-biopsies were compared against forceps biopsies in this study and demonstrated larger sample size and less crush artefact favouring cryo- biopsy use
The most encouraging results published recently was looking at cryo-biopsy for PPL using R-EBUS guidance which demonstrated a yield of 74 and the ability to obtain 3 times larger tissue biopsies when compared to traditional forceps biopsies There were no pneumothorax in this cohort and only minor bleeding was recorded requiring bronchoscopy suction alone and no other intervention recorded
However there had been no head to head trials comparing Cryo-probe vs the gold standard CT-guided biopsy
As cryo-biopsy has very favourable side effect profile without any pneumothorax occurrence if the yield were to be non-inferior this would certainly be the preferred choice of biopsy for PPL in the future
With regards to cost analysis it has been shown that R-EBUS guided biopsy Vs CT guided biopsy has similar cost profiles for the procedure alone However the final cost of the procedure depends on the side effects experienced using each procedure making CT guided biopsy the costlier of the 2 methods
However cryo-biopsy and CT guided biopsy had not been compared in an economic analysis before
Methodology All patients with a PPL requiring a diagnosis will be eligible for the trial
Prior to the procedure Either CT guided biopsy or cryo biopsy
1 The size of the lesion will be recorded volume assessment and maximum diameter on the axial scan from the CT scan prior to procedure
If the patient is randomised to the cryo biopsy arm
1 The bronchoscopist will plan the pathway to the PPL based on the CT scans The sub segments from which the lesions could be biopsied will be pre-determined and documented If available virtual bronchoscopy will be used to confirm this navigational path to the lesion
2 Maximum time allowed to locate the lesion via R-EBUS would be 20 mins
3 The procedure will be done under the usual guidelines and practice of the centre as for a flexible bronchoscopy procedure As this is a multi-centre trial centre variation on the usual practice of bronchoscopy may vary
4 Some centres may use fluoroscopy in addition to localise the lesion This is also acceptable in the protocol
5 If an endobronchial lesion is found then the patient is excluded
6 Once flexible bronchoscopy is introduced the pre-determined desired segment the R-EBUS is inserted covered by the GS
7 Once the R EBUS locates the lesion the GS is left in situ and the USS probe is retracted
8 The cryo probe is then inserted through the GS to the desired location Flexible Cryo probe outer diameter 19 mm will be applied for 4 seconds for each biopsy
9 The probe will be retracted together with the GS and the bronchoscope en masse after each biopsy
10 A minimum of 1 and maximum of 3 samples will be taken
11 A CXR is taken within 1-hour post procedure to access for pneumothorax
12 Adverse events during the procedure will be recorded as Minor bleeding requiring cold saline or adrenalin moderate bleeding requiring a bronchial blocker or APC and a large bleed requiring blood transfusion FFP cardiothoracic support etc
13 If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively Minor bleeding will not be considered an additional cost as this occurs with routine bronchoscopy
If the patient is randomised to the CT biopsy arm
1 The interventional radiologist will decide on the best position for the patient to stay during the procedure
2 A core biopsy will be performed as per usual practice of that centre In CMDHB all CT guided biopsies are performed as core biopsies
3 The patient will have 2-6 biopsies from the PPL
4 Patient lies on the side of the biopsy for 1 hour post procedure Post procedure monitoring will be performed as per usual practice
5 A CXR 1 hour post procedure will be performed to assess for pneumothorax or procedure related bleeding
6 If a chest tube placement other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively
At the pathology
All samples will be assessed for area of specimen to assess the size The ability to perform molecular typing will be documented
An independent pathologist will assess samples
Economic analysis
For both procedures Both direct costs From the hospital records and indirect cost by administering a patient questionnaire will be recorded
The main aim of cost analysis is to calculate the cost of side effect management in each arm to determine the most cost effective method of sampling a PPL
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None