Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis

NCT02315898 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: UMich Inhaled tPA119678R01FD005393
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

Plastic bronchitis (PB) is a rare, most often pediatric disease characterized by the formation of obstructive airway casts primarily composed of fibrin. There is presently no FDA-approved pharmacotherapy for PB, but acute exacerbations of the illness are often treated with inhaled tissue plasminogen activator (tPA). To date, this is done somewhat anecdotally because there has been no safety or efficacy testing of this treatment. In addition, there is presently no reliable surrogate marker of adverse drug events. Nevertheless, in the absence of inhaled tPA treatment, PB-induced respiratory distress can be severe, often warranting urgent or emergent bronchoscopy for cast removal, or can sometimes result in respiratory failure. As such there is a significant unmet need for safety and efficacy testing of inhaled tPA and for biomarkers of drug response. Objectives and Endpoints: The objectives of this protocol are to: 1) test the safety and efficacy of an inhaled tPA regimen in children with PB; and 2) identify potential candidate biomarkers of inhaled tPA drug response. Safety endpoints will consist of the development of new, active bleeding that is systemic and/or pulmonary and/or new hematuria (defined as gross hematuria). Secondary endpoints of efficacy will also be measured (e.g., frequency of cast production). Urine and blood will also be collected for the development of potential biomarkers of inhaled tPA drug response. Funding source- FDA OOPD

Conditions

Plastic Bronchitis; Protein-Losing Enteropathies; Healthy

Keywords

children, congenital heart disease, metabolomics

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: Number of Subjects That Develop New, Active Bleeding

  The number of subjects with new systemic and/or pulmonary and/or gross hematuria

  Participants will be assessed every 24 hours (daily) for the duration of tPA treatment which was up to 4 days and at hospital discharge which typically occurred within 1 week of treatment initiation.

Secondary Outcomes (11)

• Arterial Oxygen Saturation (%)

  Participants will be assessed at screening (if applicable), just prior to treatment and daily for the duration of tPA treatment, up to 4 days, at hospital discharge (~ 1 week) and again at 30 days.

• Forced Expiratory Volume in One Second (FEV1)

  Participants will be assessed at screening (if applicable), just prior to treatment and then daily for the duration of tPA treatment, up to 4 days, at hospital discharge and again at 30 days.

• Forced Expiratory Flow 25-75% (FEF25-75)

  Participants will be assessed at screening (if applicable), just prior to treatment and then daily for the duration of tPA treatment, up to 4 days, at hospital discharge and again at 30 days.

• Forced Vital Capacity (FVC)

  Participants will be assessed at screening (if applicable), just prior to treatment and then daily for the duration of tPA treatment, up to 4 days, at hospital discharge and again at 30 days.

• Frequency of Production/Expectoration of Airway Casts

  Episodes of cast production will be assessed daily for the duration tPA treatment, up to 4 days and from hospital discharge (~1 week after treatment) up to 30 days

Study Arms (1)

Treatment-inhaled tPA

EXPERIMENTAL

All patients with plastic bronchitis enrolled into the study will receive inhaled tPA.

Drug: Treatment-inhaled tPA

Interventions

Treatment-inhaled tPA DRUG

Enrolled patients with acute plastic bronchitis (fibrin airway casts) will receive inhaled tPA treatment. The tPA regimen will consist of 5mg every six hours for a total of 72 hours.

Also known as: alteplase, Activase

Treatment-inhaled tPA

Eligibility Criteria

• Age: 5 Years - 24 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≥ 5 years of age but ≤24 years of age and weigh at least 18.6 kg (41 lbs).
• Patients with CHD that have a history of PB with previous airway cast production and/or present with symptoms of an acute exacerbation (e.g., difficulty breathing, dyspnea) of PB that requires hospitalization. An acute exacerbation of PB is defined as either respiratory symptoms suspicious for airway cast formation and/or the expectoration of, or a bronchoscopy retrieved, fibrin PB cast.
• Patients without CHD that present with an acute exacerbation of PB, defined as the expectoration of, or a bronchoscopy retrieved, fibrin PB cast that causes acute respiratory distress (e.g., severe coughing, difficulty breathing, dyspnea) or a history of PB with pathologic evidence of fibrin airway cast production. Either a cast sample (at least ½ inch (\~4cm)) or a pathology report that documents PB cast fibrin content must be submitted to the UM pathology core.
• Must be able to use a mouthpiece nebulizer.
• Informed consent (with parental if age ≥14 years) or assent for age ≥10 and \< 14 years old with parental informed consent.

You may not qualify if:

• Known contraindication(s) to the use of tPA, including:
• active internal bleeding;
• history of cerebrovascular accident;
• recent intracranial or intraspinal surgery or trauma;
• intracranial neoplasm, intracranial arteriovenous malformation or intracranial aneurysm;
• known bleeding diathesis;
• and/or severe uncontrolled hypertension
• Body weight \>/= 100th percentile or BMI \> 30
• Known cystic fibrosis
• Currently receiving dornase-alfa and/or inhaled unfractionated or low molecular weight heparin and/or a direct acting oral anticoagulant (e.g., dabigatran, rivaroxaban)
• Inhaled unfractionated or low molecular weight heparin must be discontinued at least 72h. Inhaled dornase alfa should be discontinued no later than the time of the start of enrollment in the treatment phase. If the patient is receiving inhaled tPA, this regimen must be discontinued and transitioned to the inpatient dosing regimen (5mg Q6h) of study drug.
• Direct acting oral anticoagulants must be discontinued one week prior to the start of enrollment in the treatment phase.
• Protein losing enteropathy
• Liver dysfunction (defined as ≥ 3X the normal levels of one or both liver transaminases, AST and AST)
• Transaminase levels acquired within the last 9 months can be used to assess liver function. If previously normal and there is no clinical indication that liver function has worsened, the patient can be enrolled. If there are no transaminase values within the last 9 months, they need to be acquired as part of screening

Sponsors & Collaborators

• University of Michigan: lead
• Genentech, Inc.: collaborator

Study Sites (6)

Lucile Packard Children's Hospital, Stanford University

Palo Alto, California, 94304, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Michigan Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Caroline

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Stringer KA, Goldberg D, Chen S, Thrush P, Graham EM, Lubert A, Myers J, McLellan L, Flott T, Nasr S, Schumacher KR. A Multicenter, Open-Label Study to Assess the Safety of Nebulized Tissue Plasminogen Activator for the Acute Treatment of Pediatric Plastic Bronchitis: The PLATyPuS Trial. Pharmacotherapy. 2025 Oct;45(10):677-687. doi: 10.1002/phar.70056. Epub 2025 Sep 5.

  PMID: 40910281 DERIVED

MeSH Terms

Conditions

Protein-Losing Enteropathies; Heart Defects, Congenital

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Limitations and Caveats

This was a small (n=8) safety trial of inhaled tPA in pediatric patients with the extraordinarily rare disease, plastic bronchitis. As such, no statistical analysis can confidently be performed so the findings are descriptive.

Results Point of Contact

• Title: Dr. Kathleen Stringer
• Organization: University of Michigan

stringek@med.umich.edu

734-647-4775

Study Officials

• Kathleen A Stringer, PharmD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 12, 2014
• Study Start: March 19, 2018
• Primary Completion: March 5, 2021
• Study Completion: June 30, 2023
• Last Updated: August 19, 2025
• Results First Posted: November 1, 2023

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (6)