Prophylactic Endobronchial Tranexamic Acid to Reduce Bleeding in Transbronchial Cryobiopsy (CRYOTXA)

Transbronchial cryobiopsies are common procedures used to obtain tissue samples from airways for diagnostic purposes. While these procedures are safe, there is a risk of bleeding from the biopsy site. We are conducting a research study to assess the safety and effectiveness of using tranexamic acid prior to undergoing a transbronchial cryobiopsy.

Study Overview

• Status: Active, not recruiting
• Conditions: Endobronchial Mass; Hemorrhage Lung
• Intervention / Treatment: Drug: Tranexamic acid

Detailed Description

Prophylactic tranexamic acid will be instilled via endobronchial route in all patients undergoing transbronchial cryobiopsy. The medication will be administered through the bronchoscope one minute prior to the cryobiopsy. 500 mg of TXA diluted in 10 ml of saline and the procedure would be carried out as usual.

The study will be a prospective, single-arm, non-randomized trial Location: Ascension Via Christi Saint Francis. Medication: Tranexamic acid 500 milligrams per 5 mL ampule (Baxter, NDC 43066-008-01) mixed with 10 mL normal saline.

Patients: A total of 100 patients will be enrolled in the study.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18
• Signed informed consent
• Receiving a transbronchial cryobiopsy

Exclusion Criteria:

• Age below 18
• Pregnancy
• Bleeding diathesis (INR >1.5 or known hematological problems)
• Subarachnoid hemorrhage
• Any active bleeding (any site)
• Decompensated liver disease
• Active intravascular clotting
• Prior VTE
• On oral contraceptive therapy
• Platelet count less than 50,000
• Use of antiplatelet medication other than low-dose aspirin within 5 days of procedure
• Use of therapeutic anticoagulation within the last 24 hrs
• Known severe pulmonary hypertension (pulmonary artery systolic pressure > 60 mmHg)
• Chronic renal failure (estimated GFR below 30 mL/min)
• Allergy or hypersensitivity to tranexamic acid or any of its ingredients
• Prisoners
• Comfort care planned or initiated within 72 hours of admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Prophylactic TXA arm	Drug: Tranexamic acid; Prophylactic tranexamic acid will be instilled via endobronchial route in all patients undergoing transbronchial cryobiopsy. The medication will be administered through the bronchoscope one minute prior to the cryobiopsy. 500 mg of TXA diluted in 10 ml of saline and the procedure would be carried out as usual.
No Intervention: Control; Data collected retrospectively from patients undergoing the same procedure one year prior to the study initiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Hemorrhage	Ordinal scale of less severe to most severe 1. No hemorrhage 2. Minor hemorrhage 3. Intermediate hemorrhage 4. Major hemorrhage	up to 2 hours post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early termination of the procedure due to bleeding		up to 2 hours post procedure
Rate of intermediate hemorrhage		up to 2 hours post procedure
Rate of minor hemorrhage		up to 2 hours post procedure
Inadequate tissue sampling due to bleeding	y/n	up to 2 hours post procedure
Graded use of other measures to control bleeding (not prophylactic)	In order of escalating interventions (severity): use of iced saline, epinephrine, mainstem intubation, embolization	up to 2 hours post procedure
Unplanned hospital admission for bleeding complications	hospital readmission	2 hours post procedure uo to 30 days post procedure
Acute cardiovascular side effects	thrombosis events	up to 30 days post procedure
All cause 28 day mortality	morality rate	up to 28 days post procedure

Collaborators and Investigators

• Sponsor: Youssef Yammine
• Collaborators: Youssef Yammine, MD; Abdel-Ghanie H. Abu-Samra, MD; Erica N Krantz, PharmD, BCCCP; Abdul Rahman Akkawi, MD; Craig Beavers, DO; Elio Junior Feghali, MD; Patrick Evans, PharmD, BCPS

Publications and helpful links

General Publications

• Pabinger I, Fries D, Schochl H, Streif W, Toller W. Tranexamic acid for treatment and prophylaxis of bleeding and hyperfibrinolysis. Wien Klin Wochenschr. 2017 May;129(9-10):303-316. doi: 10.1007/s00508-017-1194-y. Epub 2017 Apr 21.
• Babiak A, Hetzel J, Krishna G, Fritz P, Moeller P, Balli T, Hetzel M. Transbronchial cryobiopsy: a new tool for lung biopsies. Respiration. 2009;78(2):203-8. doi: 10.1159/000203987. Epub 2009 Feb 21.
• Marquez-Martin E, Vergara DG, Martin-Juan J, Flacon AR, Lopez-Campos JL, Rodriguez-Panadero F. Endobronchial administration of tranexamic Acid for controlling pulmonary bleeding: a pilot study. J Bronchology Interv Pulmonol. 2010 Apr;17(2):122-5. doi: 10.1097/LBR.0b013e3181dc8c17.
• Cai J, Ribkoff J, Olson S, Raghunathan V, Al-Samkari H, DeLoughery TG, Shatzel JJ. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur J Haematol. 2020 Feb;104(2):79-87. doi: 10.1111/ejh.13348. Epub 2019 Dec 16.
• Hetzel J, Eberhardt R, Petermann C, Gesierich W, Darwiche K, Hagmeyer L, Muche R, Kreuter M, Lewis R, Ehab A, Boeckeler M, Haentschel M. Bleeding risk of transbronchial cryobiopsy compared to transbronchial forceps biopsy in interstitial lung disease - a prospective, randomized, multicentre cross-over trial. Respir Res. 2019 Jul 5;20(1):140. doi: 10.1186/s12931-019-1091-1.
• Bendstrup E, Kronborg-White S, Poletti V, Folkersen B, Voldby N, Rasmussen TR. Careful Planning Reduces Cryobiopsy Complications. Ann Am Thorac Soc. 2017 Jul;14(7):1229. doi: 10.1513/AnnalsATS.201703-196LE. No abstract available.
• Zhou GW, Zhang W, Dong YC, Huang HD, Hu C, Sun J, Jin F, Gu Y, Li Q, Li S. Flexible bronchoscopy-induced massive bleeding: A 12-year multicentre retrospective cohort study. Respirology. 2016 Jul;21(5):927-31. doi: 10.1111/resp.12784. Epub 2016 Apr 8.
• Kuint R, Levy L, Cohen Goichman P, Huszti E, Abu Rmeileh A, Shriki O, Abutbul A, Fridlender ZG, Berkman N. Prophylactic use of tranexamic acid for prevention of bleeding during transbronchial lung biopsies - A randomized, double-blind, placebo-controlled trial. Respir Med. 2020 Nov;173:106162. doi: 10.1016/j.rmed.2020.106162. Epub 2020 Sep 21.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Prophylaxis; Hemorrhage; Transbronchial biopsy; Tranexamic Acid (TXA)
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: CRYOTXA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No