Clinical Trial: Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Safety and Efficacy of Inhaled Tissue Plasminogen Activator (tPA) for the Acute Treatment of Pediatric Plastic Bronchitis

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 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.


Detailed Summary:
Sponsor: University of Michigan

Current Primary Outcome: 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 ]

Development of new, active bleeding that is systemic and/or pulmonary


Original Primary Outcome: 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 ]

Current Secondary Outcome:

  • 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 ]
    Frequency of production/expectoration and size of airway casts (weight and length)
  • 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 ]
    Requirement for urgent or emergent bronchoscopy and/or mechanical ventilation
  • 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 ]
    Measurement of fibrin and mucin content of airway casts
  • 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 ]
    Changes in oxygen saturation will be monitored by pulse oximetry
  • Efficacy: Changes in respiratory rate [ Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 5 days ]
    Respiratory rate will be used as a assessment of breathing effort
  • 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 ]
    Chest x-ray will be scored prior to and after tPA treatment
  • Efficacy: Detection of fibrin degradation products (FDP) 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 ]
    Blood samples will be assayed for FDP during the study


Original Secondary Outcome:

  • 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 ]


Information By: University of Michigan

Dates:
Date Received: December 8, 2014
Date Started: June 2017
Date Completion: December 2021
Last Updated: April 16, 2017
Last Verified: April 2017