Comparison of Transbronchial Cryobiopsy and Forceps Biopsy in Lung Transplant Recipients

Study Overview
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Brief Summary
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CLAD is defined as loss of lung function after other factors, particularly infections have been excluded. Readily accessible diagnostic procedures to detect acute cellular rejection at the earliest possible occasion is crucial for posttransplant survival. Serial lung function tests, laboratory testing and pulmonary imaging are only clinical indicators of chronic allograft dysfunction in lung transplant recipients. Since forceps biopsy to detect acute cellular rejection in lung transplant recipients has several shortcomings, the purpose of this study is to investigate a new biopsy technique using the transbronchial cryoprobe.

Detailed Description
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Eventually, histopathological confirmation is indispensable to establish the diagnosis of acute cellular rejection. The current gold standard for diagnosis and grading of acute cellular rejection in order to initialize the optimal treatment, with particular regard to adjusting immunosuppression, is forceps biopsy to obtain ≥ five samples. Forceps biopsy has a reasonable risk profile in experienced centers and is performed 2, 4, 6 and 12 months posttransplant and when indicated. Given these concerns about diagnostic yield in forceps biopsy and unjustifiable risks after surgical lung biopsy, cryobiopsy has arisen as promising alternative diagnostic procedure. The value of cryobiopsy to obtain a conclusive diagnosis of ACR is discussed controversially due the lack of safety and efficacy data in lung transplant recipients

Official Title
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Comparison of Transbronchial Cryobiopsy and Forceps Biopsy in Lung Transplant Recipients: A Prospective Analysis for Acute Cellular Rejection

Conditions
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Lung Transplant Rejection, Lung Transplant Failure and Rejection

Intervention / Treatment
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* Procedure: CB study arm
* Procedure: FB-CB study arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: routinely performed surveillance bronchoscopy and when indicated including serial FB and CB in the same session in patients wo had undergone lung transplant male or female subject of at least 18 years of age written informed consent after participant's information signed by patient Exclusion Criteria: age < 18 years Lacking ability to form an informed consent (including impaired judgement, communication barriers) Contraindication against bronchoscopy (e.g. co-morbidities) INR > 2 or Thrombocytes < 50000 Double antiplatelet drugs (e.g. ASS and Clopidogrel) within 7 days before biopsy Anticoagulation with NOAK within 48 hours before biopsy Moderate or severe pulmonary hypertension (mPAP > 30 mmHg, RV/RA >30 mmHg)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective randomized trial to assess diagnostic accuracy and safety of cryobiopsy using two different transbronchial biopsy techniques. Included patients are 1:1 randomized to receive either cryobiopsy (CB study arm) or forceps biopsy and cryobiopsy within the same session (FB-CB study arm). Both, forceps biopsy and cryobiopsy are performed according to official recommendations. The biopsies will be scored for ACR according to the ISHLT criteria (A0 - A4) by 3 pathologists. A subgroup analysis in the FB-CB study arm will compare FB and CB of the same patient in order to prevent second bronchoscopy due to inconclusive histological result of FB and lung function decline being suspicious for ACR.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CB study arm<br>Included patients are 1:1 randomized to receive either CB (CB study arm) or FB and CB within the same session (FB-CB study arm | Procedure: CB study arm<br>* Included patients are randomized to receive cryobiopsy<br>|
| Active Comparator: FB-CB study arm<br>Included patients are 1:1 randomized to receive either CB (CB study arm) or FB and CB within the same session (FB-CB study arm | Procedure: FB-CB study arm<br>* Included patients are randomized to receive forceps biopsy and cryobiopsy within the same session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diagnostic yield | To investigate the diagnostic yield of two different transbronchial lung biopsy techniques (forceps and cryobiopsy) for diagnosis of acute cellular rejection in lung transplant recipients. | up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of patients with treatment alteration due to the biopsy result | Impact on treatment decisions depending of the pathology results | up to 1 month | 
| Incidence of treatment-emergent adverse events as assessed by pneumothorax rate | data on safety | up to 1 week | 
| Incidence of treatment-emergent adverse events as assessed by bleeding events | data on safety | up to 1 week | 
| interobserver agreement between 3 pathologists | The biopsies are assessed for acute cellular rejection by three pathologists. | up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryobiopsy, Transbronchial Biopsy