Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis - Full Text View

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.

Funding source- FDA OOPD

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


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (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:

MedlinePlus related topics: Acute Bronchitis

Drug Information available for: Alteplase

U.S. FDA Resources

Further study details as provided by Kathleen A. Stringer, 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 ]
Development of new, active bleeding that is systemic and/or pulmonary

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 ]
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


Estimated Enrollment:	24
Anticipated Study Start Date:	August 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:

greater than or equal to 5years of age but less than or equal to16 years of age
Patients presenting with acute exacerbation of PB or a history of PB with previous pathologic evidence of fibrin airway cast production
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 -

Exclusion Criteria:

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
Known cystic fibrosis
Currently receiving inhaled tPA and/or dornase-alpha
Protein losing enteropathy
Liver dysfunction (defined as >3X the normal levels of liver function tests)
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)
International normalized ratio (INR) > 2.0 if not receiving warfarin
Patients being actively treated for thrombosis
Concomitant use of a thienopyridine class antiplatelet agent (e.g., clopidogrel)
A platelet count of < 100,000 platelets/μL
A hematocrit <35% (females) or <40% (males)
Gross hematuria or 2+ microscopic hematuria on screening urinalysis
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
Contact: Kurt R Schumacher, MD	734-615-2369	kurts@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 R01FD005393 ( U.S. FDA Grant/Contract )
Study First Received:	December 8, 2014
Last Updated:	June 16, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Study data will be shared in accordance with the NIH's policy on data sharing. The University of Michigan has options for data repository (e.g., ICPSR, http://www.icpsr.umich.edu/icpsrweb/deposit/). All metabolomics data will be deposited in the NIH's Metabolomics Workbench (http://www.metabolomicsworkbench.org/). The study PI will also honor requests made by individual investigators.


Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

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 August 18, 2017