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Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2016 by University of Michigan
Sponsor:
Information provided by (Responsible Party):
Kathleen A. Stringer, University of Michigan
ClinicalTrials.gov Identifier:
NCT02315898
First received: December 8, 2014
Last updated: October 24, 2016
Last verified: October 2016
  Purpose

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 or 2+ microscopic 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.


Condition Intervention Phase
Plastic Bronchitis
Drug: Inhaled tissue plasminogen activator (tPA)
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Inhaled Tissue Plasminogen Activator (tPA) for the Acute Treatment of Pediatric Plastic Bronchitis

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Primary Endpoint (safety): development of new, active bleeding that is systemic and/or pulmonary [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]

Secondary Outcome Measures:
  • Efficacy: Frequency of production/expectoration and size of airway casts (weight and length) [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]
  • Efficacy: Requirement for urgent or emergent bronchoscopy and/or mechanical ventilation [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]
  • Efficacy: Measurement of fibrin and mucin content of airway casts [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]
  • Efficacy: Changes in oxygen saturation (as determined by pulse oximetry) [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]
  • Efficacy: Changes in respiratory rate [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]
  • Efficacy: Changes in the chest x-ray [ Time Frame: In advance of hospitalization and again at the time of hospital admission and again at 30 days ]
  • Efficacy: Detection of fibrin degradation products in the systemic circulation [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days and again at 30 days ]

Estimated Enrollment: 24
Study Start Date: June 2017
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
All patients enrolled into the study will receive inhaled tPA.
Drug: Inhaled tissue plasminogen activator (tPA)
Enrolled patients with acute plastic bronchitis (fibrin airway casts) will receive inhaled tPA treatment
Other Names:
  • alteplase
  • Activase

  Eligibility

Ages Eligible for Study:   5 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. greater than or equal to 5years of age but less than or equal to16 years of age
  2. Patients presenting with acute exacerbation of PB or a history of PB with previous pathologic evidence of fibrin airway cast production
  3. Must be able to use a mouthpiece nebulizer
  4. Informed consent (with parental if age > 14 years) or assent for age > 10 and < 14 years old with parental informed consent -

Exclusion Criteria:

  1. 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, arteriovenous malformation or aneurysm; • known bleeding diathesis;
    • and/or severe uncontrolled hypertension
  2. Known cystic fibrosis
  3. Currently receiving inhaled tPA and/or dornase-alpha
  4. Protein losing enteropathy
  5. Liver dysfunction (defined as >3X the normal levels of liver function tests)
  6. Need for concomitant intravenous or sub-cutaneous anti-coagulation with resulting anti- Xa levels > 0.5 (low molecular weight heparins) or > 0.3 (unfractionated heparin)
  7. International normalized ratio (INR) > 2.0 if not receiving warfarin
  8. Patients being actively treated for thrombosis
  9. Concomitant use of a thienopyridine class antiplatelet agent (e.g., clopidogrel)
  10. A platelet count of < 100,000 platelets/μL
  11. A hematocrit <35% (females) or <40% (males)
  12. Gross hematuria or 2+ microscopic hematuria on screening urinalysis
  13. Pregnant or lactating women (negative pregnancy test required for girls/women of -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02315898

Contacts
Contact: Kathleen A Stringer, PharmD 734-647-4775 stringek@umich.edu

Sponsors and Collaborators
University of Michigan
  More Information

Responsible Party: Kathleen A. Stringer, Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT02315898     History of Changes
Other Study ID Numbers: UMich Inhaled tPA119678
Study First Received: December 8, 2014
Last Updated: October 24, 2016

Additional relevant MeSH terms:
Bronchitis
Acute Disease
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Disease Attributes
Pathologic Processes
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 28, 2017