Trial Search Results

Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis

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

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

University of Michigan

Collaborator: Genentech, Inc.

Stanford Investigator(s):

Intervention(s):

  • Drug: Treatment-inhaled tPA

Phase:

Phase 2

Eligibility


Inclusion Criteria (patients with plastic bronchitis):

   1. ≥ 5 years of age but ≤24 years of age and weigh at least 18.6 kg (41 lbs).

   2. Patients with CHD that have a history of PB with previous airway cast production.

   3. 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.

   4. Must be able to use a mouthpiece nebulizer.

   5. Informed consent (with parental if age ≥14 years) or assent for age ≥10 and < 14 years
   old with parental informed consent.

Exclusion Criteria (patients with plastic bronchitis):

   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. Body weight >/= 100th percentile or BMI > 30

   3. Known cystic fibrosis

   4. Currently receiving inhaled tPA and/or dornase-alpha and/or inhaled unfractionated or
   low molecular weight heparin

   5. Protein losing enteropathy

   6. Liver dysfunction (defined as ≥ 3X the normal levels of one or both liver
   transaminases)

   7. 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)

   8. International normalized ratio (INR) > 2.0 if not receiving warfarin

   9. Patients being actively treated for thrombosis

10. Concomitant use of a thienopyridine class antiplatelet agent (e.g., clopidogrel)

11. A platelet count of < 100,000 platelets/µL

12. A hematocrit <30%

13. Gross hematuria on screening urinalysis

14. 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.

Inclusion Criteria for Healthy Controls

   1. Healthy children ≥ 5 years of age but ≤18 years of age with no other underlying
   concomitant illness or chronic medication use (with the exception of vitamin
   supplements)

   2. Weigh at least 18.6 kg (41 lbs)

Inclusion Criteria for Healthy Fontan Controls

   1. Children ≥ 5 years of age but ≤18 years of age with uncomplicated Fontan physiology
   with no history of PB, other Fontan-associated complications (e.g., hepatopathy, PLE),
   or other concomitant illnesses (e.g., asthma).

   2. Weigh at least 18.6 kg (41 lbs)

Inclusion Criteria for PLE Fontan Controls

   1. Children ≥ 5 years of age but ≤18 years of age with Fontan physiology, no history of
   PB and a diagnosis of PLE defined as clinically symptomatic hypoproteinemia and/or
   enteral protein loss.

   2. Weigh at least 18.6 kg (41 lbs)

Exclusion Criteria for Healthy, Fontan Controls and PLE controls

   1. Exceed the 100th percentile for body weight or have a BMI greater than 30.

   2. History of post-operative chylothorax following any palliation surgery (Fontan
   patients).

   3. Known liver dysfunction per medical record review (e.g., liver transaminases of > 3X
   normal).

Ages Eligible for Study

5 Years - 24 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Melissa Jenkins
650-736-6588
Recruiting