Clinical trial NCT05006742: Comparison of Transbronchial Cryobiopsy and Forceps Biopsy in Lung Transplant Recipients
Official title: Comparison of Transbronchial Cryobiopsy and Forceps Biopsy in Lung Transplant Recipients: A Prospective Analysis for Acute Cellular Rejection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lung Transplant Rejection
Lung Transplant Failure and Rejection
Keywords: Cryobiopsy
Transbronchial Biopsy
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2021-08-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: diagnostic yield
timeFrame: up to 1 month
Secondary outcomes:
measure: % of patients with treatment alteration due to the biopsy result
timeFrame: up to 1 month
measure: Incidence of treatment-emergent adverse events as assessed by pneumothorax rate
timeFrame: up to 1 week
measure: Incidence of treatment-emergent adverse events as assessed by bleeding events
timeFrame: up to 1 week
measure: interobserver agreement between 3 pathologists
timeFrame: up to 3 months
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University hospital Zurich
Study officials:
affiliation: University of Zurich
name: Carolin Steinack
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yarmus L, Akulian J, Gilbert C, Illei P, Shah P, Merlo C, Orens J, Feller-Kopman D. Cryoprobe transbronchial lung biopsy in patients after lung transplantation: a pilot safety study. Chest. 2013 Mar;143(3):621-626. doi: 10.1378/chest.12-2290.
citation: Fruchter O, Fridel L, Rosengarten D, Raviv Y, Rosanov V, Kramer MR. Transbronchial cryo-biopsy in lung transplantation patients: first report. Respirology. 2013 May;18(4):669-73. doi: 10.1111/resp.12037.
citation: Roden AC, Kern RM, Aubry MC, Jenkins SM, Yi ES, Scott JP, Maldonado F. Transbronchial Cryobiopsies in the Evaluation of Lung Allografts: Do the Benefits Outweigh the Risks? Arch Pathol Lab Med. 2016 Apr;140(4):303-11. doi: 10.5858/arpa.2015-0294-OA. Epub 2015 Oct 21.
citation: Gershman E, Ridman E, Fridel L, Shtraichman O, Pertzov B, Rosengarten D, Rahman NA, Shitenberg D, Kramer MR. Efficacy and safety of trans-bronchial cryo in comparison with forceps biopsy in lung allograft recipients: Analysis of 402 procedures. Clin Transplant. 2018 Apr;32(4):e13221. doi: 10.1111/ctr.13221. Epub 2018 Feb 28.