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

Not Applicable

Completed

• Conditions: Loculated Empyema
• Interventions: Drug: Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg

• Registration Number: NCT04915586
• Lead Sponsor: National University of Malaysia

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-12-30
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Study First Submitted: 2021-02-21
• Status Verified: 2021-06
• Study First Submitted QC: 2021-06-04
• Last Update Submitted: 2021-06-04
• Study First Posted: 2021-06-07
• Last Update Posted: 2021-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg	Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg for total 3 doses within 24 hours Intervention Drug: Combination Alteplase and pulmozyme (DNase)

Primary Outcome Measures

Name	Time	Method
Radiographic improvement in pleural opacity on chest radiograph	Day 7	measured in percentage

Secondary Outcome Measures

Name	Time	Method
White cell count	Day 7	changes in inflammatory markers trend
length of hospitalisation	upto 30 days	days
pleural fluid volume drained	Day 7	measured in mls
the need of surgical referral	upto 30 days	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
changes in inflammatory markers C-Reactive Protein (CRP )	Day 7	reduction of inflammatory markers trend
adverse events post therapy	Day 7	pain, bleeding events, hemodynamic stability
mortality rate at day 30 post intervention	30 days	days

Trial Locations

Locations (1)

University Kebangsaan Malaysia Medical Centre; 🇲🇾 Cheras, Kuala Lumpur, Malaysia