Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs. CT Guided Biopsy for PPL

NCT02395939 | Unknown Phase 3 DMC

• 1 other identifier: CT-CROP
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer

Keywords

Cryobiopsy; Radial EBUS; Guide Sheath; Peripheral pulmonary lesions

Outcome Measures

Primary Outcomes (1)

• Diagnostic yield of cryo biopsy Vs. CT guided biopsy as measured by final histological diagnosis

  This outcome measures the efficacy of CT guided biopsy (The current Gold standard) against the new biopsy method called cryo-biopsy which has better safety profile from previous pilot studies.

  2 years

Secondary Outcomes (2)

• Safety profile as measured by the rate of pneumothorax and bleeding

  2 years

• Ability to sub type and molecular type the biopsy sample over and above the conventional radial EBUS samples

  2 years

Other Outcomes (1)

• Cost analysis between cryo biopsy and CT guided biopsy for PPL

  2 years

Study Arms (2)

CT guided core biopsy

ACTIVE COMPARATOR

In patients allocated to this arm a CT guided core biopsy will be performed

Procedure: CT guided core biopsy

Cryo-biopsy via Radial EBUS navigation

ACTIVE COMPARATOR

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.

Procedure: Cryo-biopsy via Radial EBUS navigation

Interventions

CT guided core biopsy PROCEDURE

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

CT guided core biopsy

Cryo-biopsy via Radial EBUS navigation PROCEDURE

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.

Cryo-biopsy via Radial EBUS navigation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with mediastinal adenopathy amenable to liner EBUS should have this procedure first and enrolled only if it fails to derive a diagnosis.
• Endobronchial tumour on flexible bronchoscopy
• Platelet count\>150
• International Normalised Ratio \>=1.5
• Haemoglobin\>100
• Neutrophils \>1.0
• Glomerular Filtration Rate\>30
• Liver Function Test\< 2 times upper limit of normal
• Unable to give consent/intellectually impaired

Sponsors & Collaborators

• Middlemore Hospital, New Zealand: lead

Study Sites (1)

Middlemore Hospital,

Auckland, 2025, New Zealand

RECRUITING

Related Publications (15)

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MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Samantha Herath, MBBS, FRACP

  Middlemore Hospital, New Zealand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha Herath, MBBS, MPhil, FRACP

CONTACT

0064-211298979; samantha.herath@middlmeore.co.nz

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Respiratory Physician, Intervetional bronchoscopist

Study Record Dates

• First Submitted: March 8, 2015
• First Posted: March 24, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: October 12, 2015

Record last verified: 2015-10

Locations

NZ (1)