4% Tetrasodium EDTA to Prevent Central Venous Access Device-Associated Complications: A Randomized Clinical Trial

# 4% Tetrasodium EDTA to Prevent Central Venous Access Device-Associated Complications: A Randomized Clinical Trial *Published: 2026 May 18* reported receipt of personal fees from Fraser Health Authority for salary support. Dr Vazquez-Grande reported holding an unpaid role as treasurer of the Canadian Critical Care Trials Group and, as such, being a member of its board of directors. Dr Rohrs reported receipt of grants from Fraser Health Authority. No other disclosures were reported. 28. JAMA. 2026 May 18:e267908. doi: 10.1001/jama.2026.7908. Online ahead of print. Cryobiopsy vs Forceps for Bronchoscopic Lung Biopsy: The FROSTBITE-2 Randomized Clinical Trial. Thiboutot J(1), Kapp CM(2), Illei P(3), Shofer S(4), Gilbert CR(5), DiBardino D(6), DeMaio A(7), Sethi S(8), Wahidi MM(2), Benn BS(8), Gillespie C(8), Salmon C(4), Angel L(7), Sachdeva A(9), Holden VK(9), Paez R(10), Duke JD(10), Lentz RJ(10), Vachani A(6), Pastis N(11), Molena D(12), Tackett S(13), Jones MR(14), Rahman NM(15)(16), Silvestri G(5), Maldonado F(10), Yarmus L(1); Interventional Pulmonary Outcomes Group. Collaborators: Los J, Pai C, Argento AC, Lee HJ, Latifi A, Cicenia J, Machuzak M, Gildea T, Almeida F, Shoajee S, Bridwell G, Kim R, Haas A, Lanfranco A, Hutchinson C, Mahmood K, Kim J. Author information: (1)Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland. (2)Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois. (3)Department of Pathology, Johns Hopkins University, Baltimore, Maryland. (4)Division of Pulmonary and Critical Care Medicine, Duke University, Durham, North Carolina. (5)Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston. (6)Division of Pulmonary and Critical Care Medicine, University of Pennsylvania, Philadelphia. (7)Division of Pulmonary, Critical Care, and Sleep Medicine, New York University Grossman School of Medicine, New York. (8)Division of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, Ohio. (9)Division of Pulmonary, Critical Care, and Sleep Medicine, University of Maryland, Baltimore. (10)Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, Tennessee. (11)Division of Pulmonary and Critical Care Medicine, The Ohio State University, Columbus. (12)Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. (13)Biostatistics, Epidemiology, and Data Management Core, Johns Hopkins School of Medicine, Baltimore, Maryland. (14)Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. (15)Oxford Respiratory Trials Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. (16)Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom. Comment in doi: 10.1001/jama.2026.7946. ## IMPORTANCE Bronchoscopic biopsy is conventionally performed with forceps, which can result in small specimen sizes and poor specimen quality due to crush artifact. Cryoprobe use localizes freezing at the probe tip, enabling retrieval of larger, more intact biopsy specimens. ## OBJECTIVE To evaluate the diagnostic yield of a 1.1-mm cryoprobe for transbronchial biopsy. DESIGN, SETTING, AND PARTICIPANTS This open-label, outcome assessor-masked, multicenter randomized clinical trial included 500 patients aged 18 years or older scheduled to undergo transbronchial biopsy for lung nodules or masses, lung transplant, or diffuse parenchymal lung disease. The trial was conducted in 9 US medical centers and enrolled patients between February 27, 2023, and September 11, 2024. The date of last follow-up was October 12, 2024. INTERVENTION: Patients were randomized 1:1 to transbronchial biopsy using a 1.1-mm cryoprobe (n = 250) or 2.0-mm forceps (n = 250). MAIN OUTCOMES AND MEASURES The primary outcome was diagnostic yield, defined as the percentage of patients for whom the transbronchial biopsy sample led to a specific diagnosis based on histologic examination. Of the 8 prespecified secondary analyses, key secondary analyses were the diagnostic yield for each of the 3 conditions (lung nodules or masses, lung transplant, and diffuse parenchymal lung disease) and complication rates. ## RESULTS Of 774 patients assessed for eligibility, 609 provided consent, 500 were randomized, and 490 were included in the primary analysis; the mean age was 62.6 years (SD, 12.7 years) and 252 of 500 (50.4%) were male. The primary outcome of diagnostic yield was significantly higher in patients randomized to transbronchial biopsy with cryoprobes vs forceps (217 of 245 [88.6%] vs 193 of 245 [78.8%]; absolute difference, 9.8%; 95% CI, 3.3%-16.3%; P = .003). For the key secondary analyses, compared with that of forceps, the diagnostic yield of cryoprobes was significantly higher among patients with pulmonary nodules or masses (79 of 95 [83.2%] vs 68 of 97 [70.1%]; absolute difference, 13.1%; 95% CI, 1.0%-24.6%; P = .04) and lung transplant (120 of 125 [96.0%] vs 110 of 124 [88.7%]; absolute difference, 7.3%; 95% CI, 0.6%-14.4%; P = .03) but did not differ significantly in diffuse parenchymal lung disease (18 of 25 [72.0%] vs 15 of 24 [62.5%]; absolute difference, 9.5%; 95% CI, -16.0% to 33.6%; P = .55). For the secondary safety analysis, there were 4 pneumothoraces requiring chest tube placement in the forceps group (1.6%) vs none in the cryoprobe group; no patients experienced significant bleeding or respiratory failure events. CONCLUSIONS AND RELEVANCE Transbronchial lung biopsy performed with a 1.1-mm cryoprobe had a significantly higher diagnostic yield compared with 2.0-mm forceps in a group of patients with lung nodules or masses, lung transplant, and diffuse parenchymal lung disease. ## TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05751278. DOI: 10.1001/jama.2026.7908 PMCID: PMC13184779 DOI: 10.1001/jama.2026.6025