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| ID | Type | Description | Link |
|---|---|---|---|
| R01FD005393 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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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
Background and Rationale: Plastic bronchitis (PB) is a rare, disease characterized by the formation of obstructive fibrin airway casts. Presently, acute exacerbations of the illness are often treated with inhaled tissue plasminogen activator (tPA), in part, because there are no FDA approved treatments. To date, there has been no safety or efficacy testing of inhaled tPA. In addition, there is presently no reliable marker that could be used to assess adverse drug events. However, 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. This clinical trial will address the unmet need for safety and efficacy testing of inhaled tPA and for assessing biomarkers of drug response.
Objectives and Endpoints: This is an open-label, multi-center clinical trial of inhaled tPA for the treatment of acute PB. 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.
Assessments: Enrolled subjects will be routinely clinically monitored and blood work will be assessed for the development of new, active bleeding that is systemic and/or pulmonary or new gross hematuria. Levels of oxygenation and pulmonary function will be assessed during the study period. We will also include the incidence of expectorated casts as a measurement of efficacy.
Statistical Methods: This is an open-label study of up to 13 subjects with PB that will serve as their own controls. A group of healthy subjects (n=12), Fontan subjects without PB (n=12), and Fontan subjects with protein losing enteropathy (PLE) (n=12) will serve as controls for biomarker assay development. The incidence of new, active bleeding events and the frequency of airway cast expectoration will be assessed in subjects with PB. PLE is another illness that is associated with congenital heart disease in children that has been surgically remedied by the Fontan procedure.
The active treatment arm (inhaled tPA) will be conducted across six clinical centers. In addition, these centers will enroll PLE control patients. All other control subjects will only be enrolled at the University of Michigan.
The outcome measures only pertain to tPA treated patients. Since the control subjects are not included in the outcome analysis, recruitment/enrollment status pertains to the PB patients. The University of Michigan has initiated enrollment of healthy control subjects and there have been consented subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment-inhaled tPA | Experimental | All patients with plastic bronchitis enrolled into the study will receive inhaled tPA. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial Oxygen Saturation (%) | Changes in oxygen saturation (%) will be monitored by pulse oximetry (oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin in the blood). Since this measurement was made at different times for each participant, the mean (SD) oxygen saturation (%) prior to study drug administration (pre-treatment) and at hospital discharge (~ 1 week post-treatment) was calculated. |
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Inclusion Criteria (patients with plastic bronchitis):
Exclusion Criteria (patients with plastic bronchitis):
Known contraindication(s) to the use of tPA, including:
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)
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
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 <30%
Gross hematuria on screening urinalysis
Pregnant or lactating women (negative pregnancy test required for girls/women of childbearing potential at the time of inhaled tPA administration). All women of child- bearing potential must be willing to practice appropriate contraception throughout the study.
Subjects who are known positive for, or are hospitalized with COVID-19 caused by the new coronavirus, SARS CoV-2, at the start of the treatment phase.
Suspected or active concurrent infectious illness.
Inclusion Criteria for Healthy Controls
Inclusion Criteria for Healthy non-PB Fontan Controls
Inclusion Criteria for PLE Fontan Controls
Exclusion Criteria for Healthy, non-PB Fontan Controls and PLE Fontan Controls
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| Name | Affiliation | Role |
|---|---|---|
| Kathleen A Stringer, PharmD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lucile Packard Children's Hospital, Stanford University | Palo Alto | California | 94304 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40910281 | Derived | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment-inhaled tPA | All patients with plastic bronchitis enrolled into the study will receive inhaled tPA. Treatment-inhaled tPA: 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. |
| FG001 | PLE Controls | Participants with congenital heart disease and protein losing enteropathy but with no history of plastic bronchitis |
| FG002 | Fontan Controls | Participants with Fontan physiology with no history of plastic bronchitis or PLE |
| FG003 | Healthy Controls | Participants without congenital heart disease and no history of pulmonary disease (including plastic bronchitis) or protein losing enteropathy |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Two participants in the Treatment arm were enrolled but were not treated because they did not have a subsequent episode of acute plastic bronchitis. One healthy control participant was enrolled and did not complete the study due to a screen failure.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment-inhaled tPA | All patients with plastic bronchitis enrolled into the study will receive inhaled tPA. Treatment-inhaled tPA: 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean (SD) age in years | Two participants in the Treatment arm were enrolled but were not treated because they did not have a subsequent episode of acute plastic bronchitis. One healthy control participant was enrolled and did not complete the study due to a screen failure. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Primary Endpoint: Number of Subjects That Develop New, Active Bleeding | The number of subjects with new systemic and/or pulmonary and/or gross hematuria | The number of new, active systemic bleeding events were assessed for participants enrolled in the treatment arm only. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. | Posted | Count of Participants | Participants | 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. |
|
30 days
For the treatment arm of the study, AEs were systematic assessed during hospitalization and tPA treatment (measurements and routine clinical assessments for bleeding). Following hospital discharge, adverse events information collection was non-systematic, self-reporting.
For the control participants, AEs were assessed at time of their one time study visit. These participants did not receive study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment-inhaled tPA | All patients with plastic bronchitis enrolled into the study will receive inhaled tPA. Treatment-inhaled tPA: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| serious adverse event | Congenital, familial and genetic disorders | Systematic Assessment | A patient received a heart transplant during the study period. This was not a study-drug related event. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| blood-tinged mucus | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kathleen Stringer | University of Michigan | 734-647-4775 | stringek@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 15, 2021 | Aug 1, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011504 | Protein-Losing Enteropathies |
| D006330 | Heart Defects, Congenital |
| ID | Term |
|---|---|
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D018376 | Cardiovascular Abnormalities |
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| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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|
| 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) | The change in FEV1 (L) from pre- to post- tPA treatment will be assessed for each patient. | 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) | The FEF25-75 will be assessed for each patient in the treatment arm prior to study drug, during study drug administration (days 0-4), at hospital discharge (~ 1 week after treatment) and again at 30 days. | 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) | The FVC (L) from prior to, during and after tPA treatment will be assessed for each patient. | 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 the production of airway casts by participants enrolled in the treatment arm will be assessed. | 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 |
| Changes in the Chest X-ray (CXR) | tPA treatment-induced changes in the CXR will be assessed. The chest x-ray will be scored prior to and after tPA treatment at hospital discharge (~1 week post treatment). The scores will be derived using the Brasfield scoring system which assesses air trapping, linear markings (bronchial wall thickness), bronchiectasis, lobar involvement and overall severity. A score of 25 represents a normal CXR. Points are deducted from 25 for abnormalities so the lower the score the greater the disease severity. | A CXR will be acquired and assessed two times during the study- once just prior to the initiation of study drug and again at hospital discharge, up to ~1 week. |
| Requirement for Urgent or Emergent Bronchoscopy | Requirement for urgent or emergent bronchoscopy during treatment was assessed. | Participants will be followed for the duration of tPA treatment, up to 4 days. |
| Requirement for Mechanical Ventilation | Requirement for mechanical ventilation will be assessed in participants enrolled in the treatment arm during the treatment period. | Participants will be followed for the duration of tPA treatment, up to 4 days. |
| Pathological Assessment (Qualitative) of Fibrin and Mucin Content of Airway Casts | PB cast fibrin and mucin content will be qualitatively assessed in casts that are collected before and after tPA treatment up to hospital discharge (~1 week) by a co-investigator pathologist. Each cast will be qualitatively assessed for fibrin and mucin content based on standard pathological procedures. | Available (submitted) airway casts will assessed for the duration of the hospital stay, up to hospital discharge (~1 week). |
| Detection of Fibrin Degradation Product (FDP) in the Systemic Circulation | Blood samples will be assayed for FDP (mg/L) during the study. This is a measure of fibrin degradation in the blood and is a value that can be altered by tPA treatment. An FDP (or D-dimer) value <0.5 mg/L is considered normal. | FDP will be assessed at screening (if applicable), prior to treatment and then daily during the hospital stay (~1 week) and again at 30 days |
| Assessment of Patient Centered Outcomes | We will use a questionnaire to assess how many participants had changes in quality of life related to plastic bronchitis and its treatment during the study in participants enrolled in the treatment arm. For this, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) will be used since there is not a specific plastic bronchitis questionnaire. The CFQ-R is designed to measure impact on overall health, daily life, perceived well-being and symptoms. The CFQ-R uses a Likert scale to rate nine quality of life domains: Physical, role/school, vitality, emotion, social, body image, eating, treatment burden, health perceptions and three symptom scales: Weight, respiratory, and digestion. Each item is summed to generate a domain score. Scores range from 0 to 100, with higher scores indicating better health. | This measurement will be performed prior to tPA treatment, at hospital discharge (~ 1 week) and again at 30 days. |
| Ann & Robert H. Lurie Children's Hospital of Chicago |
| Chicago |
| Illinois |
| 60611 |
| United States |
| University of Michigan Mott Children's Hospital | Ann Arbor | Michigan | 48109 | United States |
| Cincinnati Children's Hospital | Cincinnati | Ohio | 45229 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Medical University of South Caroline | Charleston | South Carolina | 29425 | United States |
| PLE Controls |
Participants with congenital heart disease and protein losing enteropathy but with no history of plastic bronchitis |
| BG002 | Fontan Controls | Participants with Fontan physiology with no history of plastic bronchitis or PLE |
| BG003 | Healthy Controls | Participants without congenital heart disease and no history of pulmonary disease (including plastic bronchitis) or protein losing enteropathy |
| BG004 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Two participants in the Treatment arm were enrolled but were not treated because they did not have a subsequent episode of acute plastic bronchitis. One healthy control participant was enrolled and did not complete the study due to a screen failure. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Two participants in the Treatment arm were enrolled but were not treated because they did not have a subsequent episode of acute plastic bronchitis. One healthy control participant was enrolled and did not complete the study due to a screen failure. | Count of Participants | Participants |
|
| Race (NIH/OMB) | Two participants in the Treatment arm were enrolled but were not treated because they did not have a subsequent episode of acute plastic bronchitis. One healthy control participant was enrolled and did not complete the study due to a screen failure. | Count of Participants | Participants |
|
| Region of Enrollment | Two participants in the Treatment arm were enrolled but were not treated because they did not have a subsequent episode of acute plastic bronchitis. One healthy control participant was enrolled and did not complete the study due to a screen failure. | Number | participants |
|
|
|
| Secondary | Arterial Oxygen Saturation (%) | Changes in oxygen saturation (%) will be monitored by pulse oximetry (oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin in the blood). Since this measurement was made at different times for each participant, the mean (SD) oxygen saturation (%) prior to study drug administration (pre-treatment) and at hospital discharge (~ 1 week post-treatment) was calculated. | Oxygen saturation was assessed at screening (if applicable), prior to treatment and daily for the duration of tPA treatment, at hospital discharged and at 30 days. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. Because pulse oximetry was measured at different times during hospitalization across patients, we report the mean pre-treatment and the hospital discharge (~1 week post-treatment) mean (SD) values. | Posted | Mean | Standard Deviation | percent | 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. |
|
|
|
| Secondary | Forced Expiratory Volume in One Second (FEV1) | The change in FEV1 (L) from pre- to post- tPA treatment will be assessed for each patient. | The FEV1 (L) was assessed prior to and during inhaled tPA treatment, at hospital discharge and at the 30 d follow up visit. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. Many treatment arm participants did not have values at all time points.The outcome measure is the pre-treatment average, the overall average during treatment (days 0-4) and the average at hospital discharge (~ 1 week) after treatment initiation. | Posted | Mean | Standard Deviation | Liters | 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. |
|
|
|
| Secondary | Forced Expiratory Flow 25-75% (FEF25-75) | The FEF25-75 will be assessed for each patient in the treatment arm prior to study drug, during study drug administration (days 0-4), at hospital discharge (~ 1 week after treatment) and again at 30 days. | The FEF25-75 will be assessed for each patient in the treatment arm. This is because the outcome measures were per-specified to collect data only from the treatment-inhaled tPA arm of the study. Many treatment arm participants did not have values at all time points.The outcome measure is the pre-treatment average, the overall average during treatment (days 0-4) and the average at hospital discharge (~ 1 week) after treatment initiation. | Posted | Mean | Standard Deviation | Liters/second | 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. |
|
|
|
| Secondary | Forced Vital Capacity (FVC) | The FVC (L) from prior to, during and after tPA treatment will be assessed for each patient. | The FVC (L) before, during and after tPA treatment will be assessed. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. Many treatment arm participants did not have values at all time points.The outcome measure is the pre-treatment average, the overall average during treatment (days 0-4) and the average at hospital discharge (~ 1 week) after treatment initiation. | Posted | Mean | Standard Deviation | Liters | 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. |
|
|
|
| Secondary | Frequency of Production/Expectoration of Airway Casts | Episodes of the production of airway casts by participants enrolled in the treatment arm will be assessed. | Assessment of cast production during the study period was made in the PB treatment arm only. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. This was based on self report. Cast sizes were not assessed or reported. The cumulative number of episodes of cast production reported at 30 days is reported. | Posted | Number | episodes of cast production (30d) | 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 |
|
|
|
| Secondary | Changes in the Chest X-ray (CXR) | tPA treatment-induced changes in the CXR will be assessed. The chest x-ray will be scored prior to and after tPA treatment at hospital discharge (~1 week post treatment). The scores will be derived using the Brasfield scoring system which assesses air trapping, linear markings (bronchial wall thickness), bronchiectasis, lobar involvement and overall severity. A score of 25 represents a normal CXR. Points are deducted from 25 for abnormalities so the lower the score the greater the disease severity. | All patients that received tPA. CXRs were scored by a pediatric pulmonologist using the Brasfield scoring system. A score of 25 represents a normal CXR. Points are deducted from 25 for abnormalities so the lower the score the greater the disease severity. This outcome was pre-specified for the treatment arm of the study only; CXRs were not obtained in the control arms. | Posted | Mean | Standard Deviation | score on a scale (0-25 normal) | A CXR will be acquired and assessed two times during the study- once just prior to the initiation of study drug and again at hospital discharge, up to ~1 week. |
|
|
|
| Secondary | Requirement for Urgent or Emergent Bronchoscopy | Requirement for urgent or emergent bronchoscopy during treatment was assessed. | The number of treatment arm participants who required urgent or emergent bronchoscopy was recorded. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. | Posted | Count of Participants | Participants | Participants will be followed for the duration of tPA treatment, up to 4 days. |
|
|
|
| Secondary | Requirement for Mechanical Ventilation | Requirement for mechanical ventilation will be assessed in participants enrolled in the treatment arm during the treatment period. | The number of participants in the treatment arm who required mechanical ventilation was recorded. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. | Posted | Count of Participants | Participants | Participants will be followed for the duration of tPA treatment, up to 4 days. |
|
|
|
| Secondary | Pathological Assessment (Qualitative) of Fibrin and Mucin Content of Airway Casts | PB cast fibrin and mucin content will be qualitatively assessed in casts that are collected before and after tPA treatment up to hospital discharge (~1 week) by a co-investigator pathologist. Each cast will be qualitatively assessed for fibrin and mucin content based on standard pathological procedures. | Any PB casts that were expectorated by treatment participants were sent for pathological analysis of casts by UM pathology. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. None of the PB-tPA treated study participants produced and submitted airway casts for pathological assessment. Therefore, no data are available for this outcome measure. | Posted | Available (submitted) airway casts will assessed for the duration of the hospital stay, up to hospital discharge (~1 week). |
|
|
| Secondary | Detection of Fibrin Degradation Product (FDP) in the Systemic Circulation | Blood samples will be assayed for FDP (mg/L) during the study. This is a measure of fibrin degradation in the blood and is a value that can be altered by tPA treatment. An FDP (or D-dimer) value <0.5 mg/L is considered normal. | Blood levels of FDP were assessed from participants in the treatment arm of the study. This is because the outcome measures were pre-specified to collect data only from the treatment-inhaled tPA arm of the study. The pre-treatment average of participants and the post-treatment average (at hospital discharge, ~ 1 week from the start of treatment) are reported. | Posted | Mean | Standard Deviation | mg/L | FDP will be assessed at screening (if applicable), prior to treatment and then daily during the hospital stay (~1 week) and again at 30 days |
|
|
|
| Secondary | Assessment of Patient Centered Outcomes | We will use a questionnaire to assess how many participants had changes in quality of life related to plastic bronchitis and its treatment during the study in participants enrolled in the treatment arm. For this, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) will be used since there is not a specific plastic bronchitis questionnaire. The CFQ-R is designed to measure impact on overall health, daily life, perceived well-being and symptoms. The CFQ-R uses a Likert scale to rate nine quality of life domains: Physical, role/school, vitality, emotion, social, body image, eating, treatment burden, health perceptions and three symptom scales: Weight, respiratory, and digestion. Each item is summed to generate a domain score. Scores range from 0 to 100, with higher scores indicating better health. | The number of participants enrolled in the treatment arm who had a relevant change in CTQ-R questionnaire domain scores from pre-treatment to hospital discharge were not able to be assessed because there were no participants who completed questionnaires at these two time points. No data are available for this secondary outcome. | Posted | This measurement will be performed prior to tPA treatment, at hospital discharge (~ 1 week) and again at 30 days. |
|
|
| 0 |
| 8 |
| 1 |
| 8 |
| 8 |
| 8 |
| EG001 | PLE Controls | Participants with congenital heart disease and protein losing enteropathy but with no history of plastic bronchitis | 0 | 8 | 0 | 8 | 0 | 8 |
| EG002 | Fontan Controls | Participants with Fontan physiology with no history of plastic bronchitis or PLE | 0 | 9 | 0 | 9 | 0 | 9 |
| EG003 | Healthy Controls | Participants without congenital heart disease and no history of pulmonary disease (including plastic bronchitis) or protein losing enteropathy | 0 | 12 | 0 | 12 | 1 | 12 |
|
| coughing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dizziness | Cardiac disorders | Systematic Assessment |
|
| emesis | Gastrointestinal disorders | Systematic Assessment |
|
| hypoxemia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| nose bleed | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| vasovagal response to venipuncture | Vascular disorders | Systematic Assessment |
|
| Atrial Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | Systematic Assessment |
|
| Loose stools | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Poor appetite and constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Febrile to 39.1 | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Erythematous and congested throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Increased pleural effusion on chest x-ray | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Patchy lobe atelectasis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rhinovirus | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Low blood pressure | Vascular disorders | Systematic Assessment |
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| Abnormal labs on day 30 IgG, D-dimer | Blood and lymphatic system disorders | Systematic Assessment |
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| Elevated D-dimer | Blood and lymphatic system disorders | Systematic Assessment |
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| Hematuria | Blood and lymphatic system disorders | Systematic Assessment |
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| Elevated WBC count | Immune system disorders | Systematic Assessment |
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| Systemic inflammatory response syndrome | Immune system disorders | Systematic Assessment |
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Not provided
Not provided
Not provided
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
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| Hospital Discharge (~1 week) |
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| Hospital discharge (~1 week) |
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| Hospital discharge (~1 week) |
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