Intrapleural Fibrinolytic Therapy for Empyema and Pleural Loculation: Knowns and Unknowns

Idell, Steven; Rahman, Najib M.

doi:10.1513/annalsats.201711-848ps

Cited by 24 publications

(23 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the inception of IPFT (7, 23), a number of fibrinolysins, which activate plasminogen to form plasmin and lyse fibrin, have been used to treat adults with CPE/empyema (19,24). In previous meta-analyses, it was concluded that there was equivocal evidence supporting the use of IPFT for these patients (8,9), with a more recent study unable to assess the impact of IPFT (10).…”

Section: Discussionmentioning

confidence: 99%

“…In previous meta-analyses, it was concluded that there was equivocal evidence supporting the use of IPFT for these patients (8,9), with a more recent study unable to assess the impact of IPFT (10). Among factors contributing to the uncertainty, IPFT dosing remains empiric, and bioactivity of currently used IPFT agents was not confirmed in prior clinical trial testing in adults with empyema/CPE (19,20,25).…”

Section: Discussionmentioning

confidence: 99%

“…A major impediment to interpretation of all trials concerning the efficacy and safety of IPFT to date has been that the dosing of IPFT has been empiric, with dosing of all forms of IPFT subject to arbitrary rather than evidence-based selection (19,20). We are unaware of any previous phase I dose-escalation trials done to establish dosing and safety as a prelude to efficacy testing in the IPFT field.…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

See 2 more Smart Citations

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Beckert¹,

Brockway²,

Simpson³

et al. 2019

JCI Insight

Self Cite

View full text Add to dashboard Cite

Conflict of interest: Lung Therapeutics Inc. (LTI) sponsored the trial. SI serves as a Founder and Chief Scientific Officer of LTI and a member of the Board of Directors of LTI, which provided funding for preparation of the drug product and for the trial. He has an equity position (first-tier conflict of interest) in the company, as does the University of Texas Horizon Fund and the UTHSCT. He has a conflict-of-interest plan acknowledging and managing these declared conflicts of interest through the UTHSCT and the UT System. He is an inventor on a patent (USPTO 7332469) held by the UT Board of Regents and licensed to LTI. AAK and GF have received funding from LTI for this study, and they and KS likewise have conflict-of-interest management plans at the UTHSCT. KPS has an equity position in LTI. AAK, GF, and SI are inventors on patent USPTO 10,175,255 B2. NR and YCGL serve as key opinion leaders for LTI, and NR is paid for input to the company. SS is a paid consultant for LTI, and JG received payment as medical monitor for the study from LTI. LB has a potential conflict of interest, having more than $50,000 funding support for personnel and laboratory work for this study from LTI. AMS received funding in the fiscal year prior to submission greater than $50,000 from GSK for 2 funded COPD trials. YCGL has led clinical trials for which Rocket Ltd. provided pleural drainage kits for patients without charge. YCGL has served as advisor to LTI and CareFusion/BD.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

See 1 more Smart Citation

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Beckert¹,

Brockway²,

Simpson³

et al. 2019

JCI Insight

Self Cite

View full text Add to dashboard Cite

show abstract

“…The use of IPFT in clinical practice is likewise predicated on the concept that increments of pleural fluid PA activity can increase intrapleural plasmin generation and fibrinolysis sufficient to improve pleural drainage and clinical outcomes [ 1 , 2 ]. IPFT is generally accepted as effective in pediatric patients and can improve outcomes in adult patients, although adult patient dosing is empiric, and no PA is currently approved for this indication [ 2 , 76 , 77 , 78 ].…”

Section: The Urokinase/urokinase Receptor Interaction and Derangemmentioning

confidence: 99%

“…Others use tPA alone or two chain urokinase where it is available. Unfortunately, the dosing, administration schedules and agents used for IPFT are all empiric, with no agent currently approved for the indication of treatment of pleural loculation and failed drainage [ 77 ]. There are relatively small reports suggesting that two chain uPA (uPA)-based IPFT may be of advantage.…”

Section: The Use Of Scupa For Treatment Of Pleural Loculationmentioning

confidence: 99%

The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review

Tucker

Idell

2021

IJMS

Self Cite

View full text Add to dashboard Cite

Pleural and parenchymal lung injury have long been characterized by acute inflammation and pathologic tissue reorganization, when severe. Although transitional matrix deposition is a normal part of the injury response, unresolved fibrin deposition can lead to pleural loculation and scarification of affected areas. Within this review, we present a brief discussion of the fibrinolytic pathway, its components, and their contribution to injury progression. We review how local derangements of fibrinolysis, resulting from increased coagulation and reduced plasminogen activator activity, promote extravascular fibrin deposition. Further, we describe how pleural mesothelial cells contribute to lung scarring via the acquisition of a profibrotic phenotype. We also discuss soluble uPAR, a recently identified biomarker of pleural injury, and its diagnostic value in the grading of pleural effusions. Finally, we provide an in-depth discussion on the clinical importance of single-chain urokinase plasminogen activator (uPA) for the treatment of loculated pleural collections.

show abstract

Pleural Disease

Cárdenas-García¹,

Maldonado²

2020

Evidence-Based Critical Care

View full text Add to dashboard Cite

Intrapleural Fibrinolytic Therapy for Empyema and Pleural Loculation: Knowns and Unknowns

Cited by 24 publications

References 16 publications

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

The Contribution of the Urokinase Plasminogen Activator and the Urokinase Receptor to Pleural and Parenchymal Lung Injury and Repair: A Narrative Review

Pleural Disease

Contact Info

Product

Resources

About