Related Experiment Video
Updated: Sep 9, 2025
Bronchial Thermoplasty: A Novel Therapeutic Approach to Severe Asthma
Published on: November 4, 2010
A Multicenter, Open-Label Study to Assess the Safety of Nebulized Tissue Plasminogen Activator for the Acute
Kathleen A Stringer1,2, David Goldberg3, Sharon Chen4
1Department of Clinical Pharmacy and the NMR Metabolomics Laboratory, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Insights
Inhaled tissue plasminogen activator (tPA) showed a safe safety profile for treating pediatric plastic bronchitis (PB), a rare airway condition. While not causing systemic bleeding, localized bleeding like epistaxis was observed.
Area of Science:
- Pediatric Pulmonology
- Cardiology
- Hematology
Background:
- Plastic bronchitis (PB) is a rare, serious complication in children with surgically palliated congenital heart disease (CHD).
- Fibrin casts in PB obstruct airways, leading to respiratory distress, with no FDA-approved treatments.
- Inhaled tissue plasminogen activator (tPA) is an off-label option for symptom relief.
Purpose of the Study:
- To evaluate the safety and tolerability of inhaled tPA in pediatric patients with acute PB.
- To assess systemic coagulation and hematological parameters during tPA treatment.
- To benchmark potential efficacy using spirometry and oxygen saturation compared to control groups.
Main Methods:
- A phase II open-label clinical trial involving 8 pediatric patients with acute PB receiving inhaled tPA (5 mg every 6 hours).
- Safety assessment included clinical laboratory tests for bleeding before, during, and after tPA administration.
- A control arm included children with Fontan-palliated CHD (with/without protein-losing enteropathy) and healthy children for efficacy benchmarking.
Main Results:
- No significant disruptions in systemic coagulation or hematological homeostasis were observed.
- Four instances of self-limiting epistaxis (nosebleeds) were the primary adverse events related to tPA.
- Inhaled tPA showed a statistically significant but moderate improvement in oxygen saturation; spirometry values remained unchanged.
Conclusions:
- Repeated doses of inhaled tPA appear safe for acute pediatric PB exacerbations, without causing systemic bleeding issues.
- Localized bleeding, such as epistaxis, is a potential side effect requiring patient monitoring.
- Larger randomized trials are necessary to confirm bleeding risks and evaluate efficacy more thoroughly.
Introduction:
Pediatric plastic bronchitis (PB) is a rare complication of surgically palliated congenital heart disease (CHD). Fibrin casts obstruct airways and can cause respiratory distress. There are no therapeutics approved by the United States Food and Drug Administration to treat PB, but inhaled tissue plasminogen activator (tPA) has been anecdotally used to relieve symptoms. We conducted a phase II open-label clinical trial to test the safety of inhaled tPA in pediatric PB.
Methods:
Patients with an acute exacerbation of PB requiring hospitalization were enrolled to test the safety of an inhaled tPA regimen (5 mg every 6 h). The primary end point was to assess the safety and tolerability of repeated doses of nebulized, inhaled tPA in pediatric patients with acute PB. Safety parameters consisted of clinical laboratories to assess bleeding, which were measured prior to, during, and after tPA treatment. To benchmark efficacy using spirometry and oxygen saturation, children with Fontan-palliated CHD without a history of PB, with and without protein losing enteropathy (PLE), and healthy children were enrolled in a control arm that did not receive tPA.
Results:
Of the 10 patients with PB screened for enrollment, eight qualified for immediate treatment with inhaled tPA. A total of 29 non-PB participants (PLE, n = 8 [10-18 yo]; CHD, n = 9 [8-17 yo]; and healthy, n = 12 [7-16 yo]) were enrolled. There were no differences in pretreatment clinical blood laboratory values of hemostasis and those during and after treatment with the study drug (primary safety outcome). However, there were four episodes of self-limiting epistaxis related to the study drug. Inhaled tPA statistically improved oxygen saturation although this was moderate and likely not clinically significant; inhaled tPA did not alter spirometry values.
Conclusion:
In this small, phase II study, repeated doses of inhaled tPA in patients with an acute exacerbation of PB did not result in disrupted systemic coagulation or hematological homeostasis or serious bleeding. However, patients should be monitored for localized bleeding. Larger, randomized trials are needed to provide more comprehensive assessments of bleeding risk and to further assess efficacy.
Trial Registration:
ClinicalTrials.gov identifier: NCT02315898.
Related Concept Videos
01:29Pulmonary Embolism II: Diagnostic Studies and Interprofessional Care
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...