ArticleJCI insight2019
Phase 1 trial of intrapleural LTI-01; single chain urokinase in complicated parapneumonic effusions or empyema.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Intra-pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema.The Cochrane database of systematic reviews · 2019Pooled it
- The LTI-01-2001 phase 2a trial of intrapleural LTI-01 in patients with infected, non-draining pleural effusions.Respiratory research · 2026Trial
- High tPA activity but absent PAI-1 and plasminogen function early in intrapleural lytic therapy.American journal of respiratory and critical care medicine · 2026Article
- Review
- Research Priorities for Malignant Pleural Organization with Loculation and Failed Drainage.Cells · 2025Review
- Perspective and update: intrapleural fibrinolytic therapy for pleural infections and other forms of pleural organization.Respiratory research · 2025Review
- Intrapleural Fibrinolytic Interventions for Retained Hemothoraces in Rabbits.International journal of molecular sciences · 2024Article
- Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator.Biomedicines · 2024Review
- Diagnosis and management of pleural infection.Breathe (Sheffield, England) · 2023Review
- Targeting the PAI-1 Mechanism with a Small Peptide Increases the Efficacy of Alteplase in a Rabbit Model of Chronic Empyema.Pharmaceutics · 2023Article
- PAI-1 Drives Septation and Clinical Outcomes in Pleural Infection.American journal of respiratory and critical care medicine · 2023Article
- Update on Novel Targeted Therapy for Pleural Organization and Fibrosis.International journal of molecular sciences · 2022Review
- Intrapleural Instillation of Sodium Bicarbonate versus Urokinase in Management of Complicated Pleural Effusion: A Comparative Cohort Study.International journal of general medicine · 2022Article
- TGF-β regulation of the uPA/uPAR axis modulates mesothelial-mesenchymal transition (MesoMT).Scientific reports · 2021Article
- Management of Pleural Infection.Pulmonary therapy · 2021Review
- Precision targeting of the plasminogen activator inhibitor-1 mechanism increases efficacy of fibrinolytic therapy in empyema.Physiological reports · 2021Article
- Advances in pleural infection and malignancy.European respiratory review : an official journal of the European Respiratory Society · 2021Article
- The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review.International journal of molecular sciences · 2021Review
- From Bedside to the Bench-A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema.Frontiers in pharmacology · 2021Review
- suPAR Surprises as a Biomarker of Invasive Outcomes in Pleural Infection.American journal of respiratory and critical care medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 10 institutions in 4 countries.
Funding
Abstract
backgroundCurrent 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 (scuPA), which is relatively resistant to PA inhibitor-1 (PAI-1), would be well-tolerated.
methodsThis 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.
resultsLTI-01 was well tolerated with no bleeding, treatment-emergent adverse events or surgical referrals (n=14 subjects). 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, increased PA and fibrinolytic activities and D-dimers. There was no systemic fibrinogenolysis, nor increments in plasma D-dimer. Decreased pleural opacities occurred in all but one subject. Both subjects receiving 800,000 IU required two doses to relieve pleural sepsis, with two other subjects similarly responding at lower doses.
conclusionLTI-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.