Short Duration High Intensity Intrapleural Alteplase With Pulmozyme in Pleural Infection Management

Study Overview
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Brief Summary
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The aim of this study was to assess the efficacy of the modified regimen short duration intrapleural 16mg alteplase (Actilyse, Boehringer Ingelheim) with 5mg DNase (Pulmozyme Hoffmann-La Roche Ltd) in patients with pleural infection.

Detailed Description
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The regimen 10 mg alteplase and 5 mg DNase twice daily that was used in MIST-2 trial is still an empiric choice. The rationale of using 3 doses of 16 mg alteplase dose (with supplementary 5 mg DNase) in our study was governed by the formulation of alteplase in our country (50 mg per ampoule); hence, it is best used within 24 hours following reconstitution as its biochemical stability up to 24 hours as assessed by in vitro clot lysis assays.

Official Title
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Short Duration High Intensity Intrapleural Alteplase With Pulmozyme (DNase) in Pleural Infection Management- Single Centre Experience

Conditions
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Loculated Empyema

Intervention / Treatment
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* Drug: Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patient with age more than 17 year old evidence of complex parapneumonic effusion or empyema; with poor pleural fluid drainage of ≤150 mL after 24 hours of insertion of chest drain clinical evidence of infection such as fever and or elevated C-reactive protein (CRP) or white-cell count complex pleural effusion proven by ultrasound pleural fluid analysis that fulfilled at least one of the characteristics: frank pus, exudative nature (according to light's criteria), gram stain or culture positive, lactate dehydrogenase (LDH) > 1000 U/L, pH < 7.2 and/or glucose level < 3.3mmol/L Exclusion Criteria: known allergy to pulmozyme or alteplase acute stroke, active bleeding diathesis major surgery in past 5 days previous pneumonectomy on the infected side bronchopleural fistula pregnancy coagulopathy (INR > 2, APTT >100, platelet count < 50,000 cells)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg for total 3 doses within 24 hours Intervention Drug: Combination Alteplase and pulmozyme (DNase) | Drug: Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg<br>* Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg for total 3 doses within 24 hours<br>* Other names: Combination Tissue Plasminogen Activator (t-PA) and Pulmozyme (DNase);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic improvement in pleural opacity on chest radiograph | measured in percentage | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pleural fluid volume drained | measured in mls | Day 7 | 
| changes in inflammatory markers C-Reactive Protein (CRP ) | reduction of inflammatory markers trend | Day 7 | 
| White cell count | changes in inflammatory markers trend | Day 7 | 
| length of hospitalisation | days | upto 30 days | 
| the need of surgical referral | if evidence of clinical deterioration post intrapleural therapy such as intrapleural haemorrhage or hypotension or less than 50% resolution of effusion on chest-xray post intrapleural therapy | upto 30 days | 
| adverse events post therapy | pain, bleeding events, hemodynamic stability | Day 7 | 
| mortality rate at day 30 post intervention | days | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intrapleural fibrinolysis, pleural infection