Usage Information
Abstract
BACKGROUND. Current dosing of intrapleural fibrinolytic therapy (IPFT) in adults with complicated parapneumonic effusion (CPE)/empyema is empiric, as dose-escalation trials have not previously been conducted. We hypothesized that LTI-01 (a single-chain urokinase [scuPA]), which is relatively resistant to plasminogen activator inhibitor–1 (PAI-1), would be well tolerated.METHODS. This was an open-label, dose-escalation trial of LTI-01 IPFT at 50,000-800,000 IU daily for up to 3 days in adults with loculated CPE/empyema and failed pleural drainage. The primary objective was to evaluate safety and tolerability, and secondary objectives included assessments of processing and bioactivity of scuPA in blood and pleural fluid (PF), and early efficacy.RESULTS. LTI-01 was well tolerated, with no bleeding, treatment-emergent adverse events, or surgical referrals (n = 14 subjects). Urokinase PA (uPA) antigen increased in PFs at 3 hours after LTI-01 (P < 0.01) but not in plasma. PF saturated active PAI-1, generated PAI-1–resistant bioactive complexes, and increased PA and fibrinolytic activities and D-dimers. There was no systemic fibrinogenolysis or increments in plasma D-dimers. Decreased pleural opacities occurred in all but 1 subject. Both subjects receiving 800,000 IU required 2 doses to relieve pleural sepsis, with 2 other subjects similarly responding at lower doses.CONCLUSION. LTI-01 IPFT was well tolerated at these doses, with no safety concerns. Bioactivity of LTI-01 IPFT was confirmed, limited to PFs, where its processing simulated that previously reported in preclinical studies. Preliminary efficacy signals including reduction of pleural opacity were observed.TRIAL REGISTRATION. ANZCT ID: ACTRN12616001442493.FUNDING. Lung Therapeutics Inc. (LTI), NIH SMARTT HHSN268201100014C (SI), UO-1 HL121841-01A1 (SI). 1R01HL130402-01A1 (AAK, GF, SI), UTHSCT AG18-09 (AAK).
Authors
Lutz Beckert, Ben Brockway, Graham Simpson, Anne Marie Southcott, Y.C. Gary Lee, Najib Rahman, Richard W. Light, Steven Shoemaker, John Gillies, Andrey A. Komissarov, Galina Florova, Timothy Ochran, William Bradley, Harrison Ndetan, Karan P. Singh, Krishna Sarva, Steven Idell
Usage data is cumulative from July 2025 through July 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,846 | 80 |
| 303 | 36 | |
| Figure | 515 | 0 |
| Table | 309 | 0 |
| Supplemental data | 246 | 2 |
| Citation downloads | 268 | 0 |
| Totals | 3,487 | 118 |
| Total Views | 3,605 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
