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

Abstract

Use of central venous access devices (CVADs) can result in catheter-associated bloodstream infection, catheter occlusion, and catheter-related venous thrombosis. EDTA is a potent anticoagulant, antimicrobial, and antibiofilm agent that can be instilled into inactive CVAD ports as a locking fluid to decrease the risk of infection and maintain patency. To determine whether a 4% tetrasodium EDTA (t-EDTA) locking fluid reduces CVAD-associated infections, occlusions, and thrombolytic use in adults treated in an intensive care unit (ICU). Pragmatic, triple-blind, multicenter, cluster-randomized crossover trial including patients older than 18 years in the ICU with a CVAD in place and at least 1 lumen not in use. The trial was conducted in 6 Canadian hospitals (3 community hospitals and 3 academic centers). The first patient was enrolled on March 22, 2022, and the date of last follow-up occurred on September 25, 2024. The ICUs were randomized to use prefilled, identical, masked syringes containing 2.5 mL of t-EDTA (intervention) or control locking fluid (saline or 4% citrate for hemodialysis lines) for all trial participants over a 3.5-month period. After a 1-month follow-up period, ICUs crossed over to the opposing treatment group for another 3.5 months, with a subsequent 1-month follow-up. The primary outcome was a composite incidence rate of CVAD-associated bloodstream infection, catheter occlusion requiring alteplase use, and/or catheter removal due to occlusion. Three of the 8 prespecified secondary outcomes included incidence rates of each component of the primary outcome separately. Of the 1574 eligible patients, 1468 (mean age, 60 [SD, 16.0] years; 37.7% female) were included in the analysis (696 receiving t-EDTA and 772 receiving control). The incidence rate of primary outcome events was 13.1 per 1000 catheter-days (74 events) in the t-EDTA group vs 19.9 per 1000 catheter-days (126 events) in the control group. In adjusted multivariate analysis, the incidence rate of the composite outcome was lower among patients receiving t-EDTA vs control (rate ratio, 0.68; 95% CI, 0.47-0.96; P = .03). Among the 3 components of the primary outcome, only the secondary outcome of CVAD occlusion requiring administration of alteplase significantly differed between the groups, with lower rates in the t-EDTA group vs control (66 vs 112; incidence rate, 11.67 and 17.73 per 1000 catheter-days, respectively; rate ratio, 0.66; 95% CI, 0.46-0.96). Compared with control locking solution, use of 4% t-EDTA locking solution for CVADs reduced the incidence of a composite outcome of CVAD-associated bloodstream infection, catheter occlusion requiring alteplase use, and catheter removal due to occlusion among adult patients in the ICU. ClinicalTrials.gov Identifier: NCT04548713.