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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02395939




Registration number
NCT02395939
Ethics application status
Date submitted
8/03/2015
Date registered
24/03/2015
Date last updated
12/10/2015

Titles & IDs
Public title
Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs. CT Guided Biopsy for PPL
Scientific 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)
Secondary ID [1] 0 0
CT-CROP
Universal Trial Number (UTN)
Trial acronym
CT-CROP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - CT guided core biopsy
Treatment: Surgery - Cryo-biopsy via Radial EBUS navigation

Active comparator: CT guided core biopsy - In patients allocated to this arm a CT guided core biopsy will be performed

Active comparator: Cryo-biopsy via Radial EBUS navigation - If the patient is randomised to this arm, the lesion will be located via R-EBUS.

Each patient will have 3 cryo biopsies and 3 forceps biopsies. The order of the cryo biopsy and forcep biopsy will be randomly allocated at the time of initial randomisation.


Treatment: Surgery: CT guided core biopsy
CT guided biopsy will be performed by a trained interventional radiologist using core biopsy.

Treatment: Surgery: Cryo-biopsy via Radial EBUS navigation
Cryo-biopsy will be performed via R-EBUS guidance. Cryo biopsy probe will be applied for 4 seconds for each biopsy and a minimum of 3 biopsies will be performed . Each patient will also have 3 forceps biopsies. The order of forceps biopsy or cryo biopsy will be randomly allocated.
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Diagnostic yield of cryo biopsy Vs. CT guided biopsy as measured by final histological diagnosis
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Safety profile as measured by the rate of pneumothorax and bleeding
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Ability to sub type and molecular type the biopsy sample over and above the conventional radial EBUS samples
Timepoint [2] 0 0
2 years

Eligibility
Key inclusion criteria
* All patients aged >18 years with a peripheral pulmonary lesion, suspected of lung cancer, requiring a biopsy
* The lesion will be included irrespective of the relationship to the bronchus or ground glass appearance.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with mediastinal adenopathy amenable to liner EBUS should have this procedure first and enrolled only if it fails to derive a diagnosis.
2. Endobronchial tumour on flexible bronchoscopy
3. Platelet count>150
4. International Normalised Ratio >=1.5
5. Haemoglobin>100
6. Neutrophils >1.0
7. Glomerular Filtration Rate>30
8. Liver Function Test< 2 times upper limit of normal
9. Unable to give consent/intellectually impaired

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2018
Actual
Sample size
Target
158
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland,

Funding & Sponsors
Primary sponsor type
Other
Name
Middlemore Hospital, New Zealand
Address
Country

Ethics approval
Ethics application status

Summary
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 intervetional,randomised 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 1.9mm) 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.
Trial website
https://clinicaltrials.gov/study/NCT02395939
Trial related presentations / publications
National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29.
Prosch H, Stadler A, Schilling M, Burklin S, Eisenhuber E, Schober E, Mostbeck G. CT fluoroscopy-guided vs. multislice CT biopsy mode-guided lung biopsies: accuracy, complications and radiation dose. Eur J Radiol. 2012 May;81(5):1029-33. doi: 10.1016/j.ejrad.2011.01.064. Epub 2011 Jul 12.
Loh SE, Wu DD, Venkatesh SK, Ong CK, Liu E, Seto KY, Gopinathan A, Tan LK. CT-guided thoracic biopsy: evaluating diagnostic yield and complications. Ann Acad Med Singap. 2013 Jun;42(6):285-90.
Montaudon M, Latrabe V, Pariente A, Corneloup O, Begueret H, Laurent F. Factors influencing accuracy of CT-guided percutaneous biopsies of pulmonary lesions. Eur Radiol. 2004 Jul;14(7):1234-40. doi: 10.1007/s00330-004-2250-3. Epub 2004 Feb 13.
Arslan S, Yilmaz A, Bayramgurler B, Uzman O, Nver E, Akkaya E. CT- guided transthoracic fine needle aspiration of pulmonary lesions: accuracy and complications in 294 patients. Med Sci Monit. 2002 Jul;8(7):CR493-7.
Wu CC, Maher MM, Shepard JA. Complications of CT-guided percutaneous needle biopsy of the chest: prevention and management. AJR Am J Roentgenol. 2011 Jun;196(6):W678-82. doi: 10.2214/AJR.10.4659.
Grasso RF, Cazzato RL, Luppi G, D'Agostino F, Schena E, Del Vescovo R, Giurazza F, Faiella E, Beomonte Zobel B. Percutaneous lung biopsies: performance of an optical CT-based navigation system with a low-dose protocol. Eur Radiol. 2013 Nov;23(11):3071-6. doi: 10.1007/s00330-013-2932-9. Epub 2013 Jun 20.
Hsiao SH, Chung CL, Lee CM, Chen WY, Chou YT, Wu ZH, Chen YC, Lin SE. Suitability of computed tomography-guided biopsy specimens for subtyping and genotyping of non-small-cell lung cancer. Clin Lung Cancer. 2013 Nov;14(6):719-25. doi: 10.1016/j.cllc.2013.06.002. Epub 2013 Jul 25.
S H. CT guided lung biospy-FNA or core biospy? Royal Australian New Zealand College of Radiology 2013;2013 Abstract
Gasparini S, Ferretti M, Secchi EB, Baldelli S, Zuccatosta L, Gusella P. Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses. Experience with 1,027 consecutive cases. Chest. 1995 Jul;108(1):131-7. doi: 10.1378/chest.108.1.131.
Baaklini WA, Reinoso MA, Gorin AB, Sharafkaneh A, Manian P. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000 Apr;117(4):1049-54. doi: 10.1378/chest.117.4.1049.
Schuhmann M, Bostanci K, Bugalho A, Warth A, Schnabel PA, Herth FJ, Eberhardt R. Endobronchial ultrasound-guided cryobiopsies in peripheral pulmonary lesions: a feasibility study. Eur Respir J. 2014 Jan;43(1):233-9. doi: 10.1183/09031936.00011313. Epub 2013 Jul 30.
Steinfort DP, Liew D, Irving LB. Radial probe EBUS versus CT-guided needle biopsy for evaluation of peripheral pulmonary lesions: an economic analysis. Eur Respir J. 2013 Mar;41(3):539-47. doi: 10.1183/09031936.00044612. Epub 2012 Jul 26.
Griff S, Ammenwerth W, Schonfeld N, Bauer TT, Mairinger T, Blum TG, Kollmeier J, Gruning W. Morphometrical analysis of transbronchial cryobiopsies. Diagn Pathol. 2011 Jun 16;6:53. doi: 10.1186/1746-1596-6-53. Erratum In: Diagn Pathol. 2016 Jul 19;11(1):64. doi: 10.1186/s13000-016-0515-1.
Hetzel J, Eberhardt R, Herth FJ, Petermann C, Reichle G, Freitag L, Dobbertin I, Franke KJ, Stanzel F, Beyer T, Moller P, Fritz P, Ott G, Schnabel PA, Kastendieck H, Lang W, Morresi-Hauf AT, Szyrach MN, Muche R, Shah PL, Babiak A, Hetzel M. Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial. Eur Respir J. 2012 Mar;39(3):685-90. doi: 10.1183/09031936.00033011. Epub 2011 Aug 18.
Public notes

Contacts
Principal investigator
Name 0 0
Samantha Herath, MBBS, FRACP
Address 0 0
Middlemore Hospital, New Zealand
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Samantha Herath, MBBS, MPhil, FRACP
Address 0 0
Country 0 0
Phone 0 0
0064-211298979
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02395939