Abstract
Backround: To evaluate the feasibility of a randomized controlled trial (RCT) of the fibrinolytic tissue plasminogen activator (t-PA) vs unfractionated heparin (UFH) central venous catheter (CVC) dwell therapy to reduce risk of CVC-associated deep venous thrombosis (CADVT) in critically ill children. Methods: This single center quadruple blinded pilot RCT enrolled children ≤18 years of age with CVC placed within 72 hours of admission to the pediatric intensive care unit (ICU)Weight-adjusted dose of study drug dwell (t-PA vs UFH) was installed to alternating lumen of CVC every 3 days for 10 doses, CVC removal or ICU discharge. Ultrasound with doppler was performed at study completion.Main Results: Of 426 children screened from April-Dec 2019, 86 (20%) were eligible with 20 enrolled and randomized. Primary outcome measure of enrollment rate was 23%. One child was withdrawn immediately after randomization due to development of exclusion criterion. Secondary feasibility outcome measures were proportion of children who received study drug within 24 hours of consent (100%), proportion with ultrasound (100%), and proportion completing the study (95%). Eighteen of 19 children received the first dose within 48 hours of CVC placement. All children missed some dose days because of lumen specified to be in continuous use. Median dwell time for doses received was >2 hours. There were no protocol violations. Six of 19 patients (31.6%) developed CADVT, 1 of which was occlusive. There were no catheter-associated blood stream infection or significant bleeding.Conclusion: Critically ill children requiring CVC are at high risk for CADVT. A future multicenter, blinded, RCT to determine the effectiveness of t-PA vs UFH dwell in reducing CADVT is feasible.Registered August 10, 2018 on ClinicalTrials.gov NCT03672006
Central Venous Catheter-directed Tissue Plasminogen Activator in Massive Pulmonary Embolism
