The LTI-01-2001 phase 2a trial of intrapleural LTI-01 in patients with infected, non-draining pleural effusions
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Single chain urokinase (LTI-01) intrapleural enzymatic therapy (IET) was safe and promising in a phase 1 clinical trial to overcome failed drainage in patients with pleural infection. The LTI-01-2001 phase 2a trial was a randomized, double-blind, placebo-controlled, multi-center, dose-ranging study in hospitalized subjects with infected, non-draining pleural effusions. METHODS: LTI-01, in doses of 400,000, 800,000 or 1,200,000 Units, or placebo was administered intrapleurally once daily for up to 3 days. The primary efficacy endpoint was incidence of treatment failure within 7 days of starting study medication. Treatment failure was defined as requiring alternative pleural therapy irrespective of subsequent treatment. Pleural opacification was a secondary endpoint and was assessed by CT imaging of the change in opacified area expressed as a percentage of the ipsilateral hemithorax (relative change) or absolute change in pleural opacification volume expressed in liters. RESULTS: 40/43 enrolled patients received LTI-01 or placebo due to constraints of the COVID-19 pandemic. There was no significant difference in incidence of treatment failure between the LTI-01 and placebo groups (OR 1.04, 95% CI 0.24,4.44, P = 0.96) while two predetermined sensitivity analyses demonstrated trends of improved efficacy in the 400,000 U group (P = 0.052 and 0.147). The absolute (Liters; L) and relative change from baseline in opacity volume were - 0.28 L (p=0.035) and - 55.8% (P = 0.064) versus placebo in the 800,000 U group, with significant reduction in absolute opacification found in the 400,000 and all LTI-01-treated groups combined (P < 0.03, respectively). There were no safety signals of concern, nor were there any episodes of intrapleural or pulmonary bleeding in LTI-01-treated patients. CONCLUSIONS: No statistically significant difference in the incidence of treatment failure was seen, potentially related to low recruitment. Trends towards efficacy were observed in predetermined sensitivity analyses at the 400,000 U dose of intrapleural LTI-01. Pleural opacification appeared most improved by the 800,000 U intrapleural LTI-01. A larger phase 2b trial is required to confirm these results or determine the efficacy of LTI-01 in patients with organizing, nondraining, infected pleural effusions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04159831. Registration date: November 12, 2019.
Source: Respiratory Research
Authors: Carla R Lamb, Jason Akulian, Ali Musani, Samira Shojaee, Alexander Chen, Jonathan Kurman, Pushan Jani, Michal Senitko, Danish Ahmad, Momen Wahidi, Sikandar Ansari, Muhanned Abu-Hijleh, Kevin C. Ma, Jonathan Puchalski, Lonny Yarmus, Fayez Kheir, Fabien Maldonado, George Cheng, Christian Alvarado, Singh P. Karan, Brian Windsor, Najib M Rahman, Steven Shoemaker, Steven Idell
Institutions: Lahey Hospital and Medical Center, University of North Carolina at Chapel Hill, Hofstra University, Lenox Hill Hospital, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Vanderbilt University Medical Center, Washington University in St. Louis, Medical College of Wisconsin, Memorial Hermann–Texas Medical Center, University of Mississippi Medical Center, Fox Chase Cancer Center, Temple University, Northwestern University, Intermountain Healthcare, LDS Hospital, The University of Texas Southwestern Medical Center, University of Pennsylvania, Johns Hopkins University, Johns Hopkins Medicine, Massachusetts General Hospital, Vanderbilt University, University of California San Diego, The University of Texas at Tyler, The University of Texas at Austin, Oxford University Hospitals NHS Trust
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
OpenAlex ID: W7164991945