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

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

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.

Study Overview

• Status: Completed
• Conditions: Loculated Empyema
• Intervention / Treatment: Drug: Intra-pleural Alteplase 16mg with Pulmozyme (DNase) 5mg

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • University Kebangsaan Malaysia Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Investigators: Principal Investigator: Mohamed Faisal Abdul Hamid, Associate professor

Publications and helpful links

General Publications

• Cheong XK, Ban AY, Ng BH, Nik Abeed NN, Nik Ismail NA, Nik Fuad NF, Syed Zakaria SZ, Ghan SL, Abdul Hamid MF. Modified regimen intrapleural alteplase with pulmozyme in pleural infection management: a tertiary teaching hospital experience. BMC Pulm Med. 2022 May 17;22(1):199. doi: 10.1186/s12890-022-01995-z. Erratum In: BMC Pulm Med. 2022 Nov 23;22(1):440.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: February 21, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: June 4, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Intrapleural fibrinolysis, pleural infection
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Suppuration; Infections; Empyema; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: FF-2020-008; NMRR-19-2940-51404 (Registry Identifier: Medical Research Ethic Committee of Ministry of Health Malaysia)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No