Pleural InfectionPENTAD-FTNCT05903417
Pleural Irrigation With Normal Saline Versus Intrapleural Fibrinolytic
A study testing Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg and Saline irrigation with 250 mls normal saline (over 1 hour) in people with Pleural Infection, run by National University of Malaysia at 1 site in Malaysia.
Trial summary
Parapneumonic effusions caused by an infection of the pleural membranes occur in 40-57% of cases of pneumonia. A variable percentage (10-20%) of parapneumonic effusions progresses to empyema (pus) and/or abscess formation (encapsulation). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pleural Infection
- What is being tested?
- Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg and Saline irrigation with 250 mls normal saline (over 1 hour)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteMalaysia
- Study dates
- 10 Jul 2023to 14 Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 1. Adult patient with aged ≥ 18 years old 2. Patients with pleural infection (complex parapneumonic effusion or empyema) with poor pleural fluid drainage of ≤ 150 ml after 24H of insertion of chest drain 3. Clinical features consistent with pleural infection ; fulfilling ≥ 2 of the following characteristics : i) Clinical evidence of infection such as fever and or elevated C-reactive protein (CRP) or total white blood count (TWBC) ii) Complex pleural effusion proven by thoracic ultrasound is defined as presence of fibrin strands or septations within pleural cavity iii) Pleural fluid that fulfil at least one of the characteristic :
- frank pus,
- exudative type of pleural effusion (according to light's criteria)
- gram stain or culture positive
- lactate dehydrogenase (LDH) > 900U/L
- Acidic with ph < 7.2
- glucose level < 3.3 mmol/L
Who cannot join
- Refusal to participate
- Known allergy to t-PA or DNase
- Acute stroke
- Significant bleeding diathesis/ active gastrointestinal bleed
- Major surgery in the previous 5 days
- Previous pneumonectomy on the infected side
Show all 10Show fewer
- Bronchopleural fistula
- Pregnancy
- Coagulapathy (INR > 2, APTT > 100)
- Platelet count < 50000 cells
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
National University of Malaysia
Kuala Lumpur, Kuala Lumpur, 56000
About this study
Official title: A Randomised Open-Label Controlled Trial of Pleural Irrigation With Normal Saline Versus Intrapleural Tissue Plasminogen Activator and DNase (Fibrinolytic Therapy) in Pleural Infection.
Parapneumonic effusions caused by an infection of the pleural membranes occur in 40-57% of cases of pneumonia. A variable percentage (10-20%) of parapneumonic effusions progresses to empyema (pus) and/or abscess formation (encapsulation). Pleural infection is associated with significant morbidity and mortality which may be as high as 20-35% in immunocompromised patients Standard treatment of these collections in adults involves antibiotic therapy, effective drainage of infected fluid and surgical intervention if conservative management fails. For parapneumonic effusions which require clearance, appropriate therapy is effective drainage via an intercostal catheter (ICC) with antibiotic therapy. The presence of fibrinous septae in the pleural space, known as loculations, may result in inadequate drainage of effusions and therefore non-resolution of infection and systemic sepsis. Without effective intercostal catheter drainage, surgical intervention (VATS or open) has usually been required to clear loculations for resolution of infection.
Non-surgical treatment options to reduce the impact of adhesions and locule include (in addition to appropriate antibiotic therapy) single and multiple thoracocentesis, or single and multiple intercostal tube thoracostomies, with or without intrapleural fibrinolytic agents.
Read more
Fibrinolytic agents including streptokinase, urokinase, alteplase and recombinant tissue plasminogen activator (rTPA) have been used safely and effectively intrapleurally for complicated pleural effusion and empyema.
MIST 2 trial has established intrapleural therapy as the mainstay of CPEE treatment hence avoiding surgery and decreasing the length of hospitalization; however, little is known about the correct dosage needed for tPA and DNase. Dose and duration of intrapleural therapy based on MIST 2 involve multiple dosing and can be time-consuming for health care providers . Previous studies showed that complexity of treatment is a factor associated with poor adherence to a regimen. For this reason, trying to find the minimum effective dose and simplifying the regimen is essential for minimizing side effects and maximizing adherence. The review of currently available literature shows concurrent administration of tPA and DNase to be safe and effective even at lower cumulative dose Other study was carried out in May 2022 in which Modified regimen intrapleural alteplase 16 mg t-PA with 5 mg DNase for total 3 doses that administered sequentially within 24 h had been used. In this study, modified regimen of t-PA and DNase offer an alternative therapeutic option for patients that are unfit or refuse surgical intervention but persistent pleural infection. They have demonstrated similar treatment success comparable to other studies, as evidenced by improvement on pleural fluid drainage and reduction in pleural opacity on day 7 chest x-ray was approximately 50% from the baseline using intrapleural 16 mg t-PA with 5 mg DNase. The mechanism of action of t-PA and DNase in pleural cavity remain unclear. Studies suggested that IPFT may trigger the monocyte chemoattractant protein 1 (MCP-1) pathway which promote pleural fluid formation and subsequently causes a therapeutic lavage effect that increases pleural fluid drainage.
Another option for intrapleural therapy may be pleural irrigation with normal saline. The idea behind is to dilute and remove bacteria, cytokines, inflammatory cells, and pro-fibrinogenic coagulation factors, which induce pleural fluid organization. Also, the mechanical process of irrigation increases pleural fluid drainage by reducing stasis and organization of the intrapleural contents .
A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care. Significantly fewer patients in the irrigation group were referred for surgery (30).
However, till date there is no study done on head to head comparison between intrapleural fibrinolytic with alteplase and DNAse Versus Pleural irrigationwith normal saline.
Read the detailed description
Problem Statement
Retained complicated pleural effusion is associated with a risk of empyema and sepsis.IPFT is commonly used as the bridging therapy to surgery. The efficacy of saline irrigation is not known. However, the probable problem in this study is when failed saline irrigation, the patient will be given IPFT as part of the intention to treat.
Research Questions:
- Is the combination of intrapleural Alteplase (t-PA) 5mg and DNase (Pulmozyme) 5mg superior than pleural pleural irrigation in the management of pleural infection?
Primary Objective:
- comparison of the safety outcome between IPFT and intrapleural saline irrigation, such as clinical deterioration, chest pain requiring escalation of analgesics, gastrointestinal bleeding, bleeding from chest drain site, intrapleural hemorrhage, hemoptysis, Hemoglobin (Hb) drop >10% from baseline requiring blood transfusion
Secondary Objectives:
- To determine the reduction of pleural opacity (in percentage) on chest radiograph from day 1 (randomization) to day 7
- To determine the change on inflammatory markers (WBC/CRP) from day 1 (randomization) to day 7
- To determine the outcome :
- Length of hospital stay (in days) after randomization for each group
- The need of surgical intervention in 30 days
- Mortality rate at 30 days
- To measure the volume of pleural effusion drainage (in mls) 48 hours following randomization
Study Hypothesis
- Subjects in the IPFT has more volume of pleural fluid drainage compared with pleural irrigation group
- Subjects in the IPFT has greater reduction of inflammatory parameters compared with pleural irrigation group
- Subjects in the IPFT has shorter length of hospital stay compared with pleural irrigation group
- Subjects in the IPFT has less surgical referral rate compared pleural irrigation group
- There is no difference of mortality rate between both groups
Subjects with pleural infection (complex parapneumonic effusion or empyema) with poor outflow ≤150cc pleural fluid from chest drain over 24 hours of insertion with standard medical therapy who are eligible for this study will be offered to participate into this study. Patient will be informed that this is an 'off label' drugs and a written informed consent will be obtained.
All patients will undergo chest tube/drain insertion. The decision to insert chest drain, the size of chest drain and when to initiate intrapleural t-PA/DNase is determined by the chest physician.
Ultrasound of thorax and chest radiograph will be performed within 24hours before randomization. Ultrasound of thorax is performed by chest physician with curve probe (ultrasound Mindray, model Z5) for confirmation of complex pleural effusions and chest tube's position. Complex pleural effusion on ultrasound is defined as fibrin strands or septa within the pleural effusion along with presence of loculations in pleural cavity. A baseline chest radiograph will be performed within 24 hours prior to intrapleural fibrinolysis or pleural irrigation to ensure the chest tube position.
Demographic data was collected prior to randomization, which consist of age,gender,ethnicity,BMI,comorbidities. Subjects will be randomized with a block of 4 (using sealed envelope) with random permutations of 2 groups : pleural irrigation group and intrapleural t-PA and DNase.
All patients that prescribed intrapleural t-PA/DNase during the study period will receive a standard dose of medications as below (Appendix 1).
Medication Regimen :
t-PA (Alteplase) 5mg and DNase (Pulmozyme)5mg t-PA (Alteplase) that is available in our pharmacy is 50mg ampoule and DNase (Pulmozyme) is 2.5mg per ampoule The number of installation of intrapleural t-PA/DNase depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5mg of Alteplase (t-PA) and 5mg DNase are diluted in each 50ml of 0.9% sodium chloride solution. t-PA and DNase are not mixed together in one syringe. The detailed method of t-PA/DNase therapy administration is described in Appendix 1. In brief , both medication are administered sequentially which t-PA is first instilled intrapleurally and the chest tube is then clamped for 45 minutes, then unclamped to allow free drainage for 45 minutes. The same procedure is then repeated for DNase. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement.
However, as for patients who were randomized into pleural irrigation group, subjects were administered 250 ml of 0.9% sodium chloride via chest tube a three way tap from a drip stand which were allowed drainage freely over 1 hour. Pleural irrigation will be performed minimum of 3 installations and maximum of 9 installation (3 times per day).
Both groups received standard care of treatment : which includes regular flushing of chest drain to maintain patency using 20mls of normal saline.
The primary outcome was to evaluate the volume of pleural effusion drainage (in mls) 72 hours following randomization. The volume drained measured after subtracting the amount of volume administered as per protocol.
The secondary outcome are measured by the change in the area of pleural opacity in chest x-ray (day 7 post t-PA/DNase compared to baseline), measured as the percentage of the ipsilateral hemithorax occupied by effusion. The area of pleural opacity and the area of the ipsilateral hemithorax will be measured digitally by two radiologists using Horos Project Software, v3.2.1 as described previously in Multicentre Intrapleural Sepsis Trial 2 (MIST-2)
Other outcomes that will be monitored include :
- Inflammatory markers including serum C-reactive protein (CRP) \& white blood count
- Length of hospital stay in days
- The need of surgical intervention within 30 days
- Adverse effects :
- Chest pain required escalation of analgesics
- Systemic bleeding
- Pleural bleeding
During any point of treatment subjects will be allowed to cross-over and analysis will be done as per intention to treat. Subjects in the pleural irrigation group may be switched to IPFT group if there is poor response to treatment (poor drainage of effusion), or adverse effects of irrigation as per clinician's judgement. On the contrary, subjects in the IPFT group may be switched to pleural irrigation group if patient developed any adverse effects of IPFT (e.g hemothorax,haemoptysis). Those who failed both treatment will be referred for surgical intervention
- Conditions
- Pleural Infection
- Being tested
- Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg, Saline irrigation with 250 mls normal saline (over 1 hour)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mgDrug
The number of installation of intrapleural t-PA/DNase depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5mg of Alteplase (t-PA) and 5mg DNase are diluted in each 50ml of 0.9% sodium chloride solution. t-PA and DNase are not mixed together in one syringe. In brief , both medication are administered sequentially which t-PA is first instilled intrapleurally and the chest tube is then clamped for 45 minutes, then unclamped to allow free drainage for 45 minutes. The same procedure is then repeated for DNase. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement.
Saline irrigation with 250 mls normal saline (over 1 hour)Other
subjects were administered 250 ml of 0.9% sodium chloride via chest tube a three way tap from a drip stand which were allowed drainage freely over 1 hour. Pleural irrigation will be performed minimum of 3 installations and maximum of 9 installation (3 times per day).
| Study group | Role | What they receive |
|---|---|---|
| Pleural Irrigation Arm | Active comparator | subjects were administered 250 ml of 0.9% sodium chloride via chest tube a three way tap from a drip stand which were allowed drainage freely over 1 hour. Pleural irrigation will be performed minimum of 3 installations and maximum of 9 installation (3 times per day). Receives: Other: Saline irrigation with 250 mls normal saline (over 1 hour) |
| Intrapleural fibrinolytic arm | Active comparator | t-PA (Alteplase) 5mg and DNase (Pulmozyme)5mg t-PA (Alteplase) that is available in our pharmacy is 50mg ampoule and DNase (Pulmozyme) is 2.5mg per ampoule The number of installation of intrapleural t-PA/DNase depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5mg of Alteplase (t-PA) and 5mg DNase are diluted in each 50ml of 0.9% sodium.
Both medication are administered sequentially which t-PA is first instilled intrapleurally and the chest tube is then clamped for 45 minutes, then unclamped to allow free drainage for 45 minutes. The same procedure is then repeated for DNase. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement. Receives: Drug: Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
to compare of the safety outcome between IPFT and intrapleural saline irrigation.
Number of participants who developed clinical deterioration, chest pain requiring escalation of analgesics, gastrointestinal bleeding, bleeding from chest drain site, intrapleural hemorrhage, hemoptysis, Hemoglobin (Hb) drop >10% from baseline requiring blood transfusion
Measured: Day 7
Secondary outcomes (5)
To measure the change in the area of pleural opacity in chest x-ray compared to baseline
measured as the percentage of the ipsilateral hemithorax occupied by effusion. The area of pleural opacity and the area of the ipsilateral hemithorax will be measured digitally by two radiologists using Horos Project Software, v3.2.1 as described previously in Multicentre Intrapleural Sepsis Trial 2 (MIST-2)
Measured: Day 7
Changes in Inflammatory markers including serum C-reactive protein (CRP) & white blood count
reduction of inflammatory markers trend
Measured: Day 7
Length of hospitalization
measured in days
Measured: through admission (up to 30 days)
the need for surgical referral
If failed intrapleural fibrinolytic or pleural irrigation (Discretion of treating physician)
Measured: throughout admission up to 30 days
to evaluate the volume of pleural effusion drainage (in mls) 72 hours following randomization.
The net volume of pleural effusion drained measured after subtracting the
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start10 Jul 2023
- Primary completion14 Oct 2025
- Study completion14 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pleural InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University of Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohamed Faisal Abdul Hamid, MBBS (IIUM), Principal investigator, National University of Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05903417
- Sponsor's protocol ID
- JEP-2023-163
- Acronym
- PENTAD-FT
- Status last verified
- Feb 2026
- First submitted
- 5 Jun 2023
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rozi SNM, Jailaini MFM, Azmel AA, Ismail NAN, Fuad NFN, Zainal IA, Ghan SL, Shah SA, Rahim MJC, Hamid MFA. A pilot randomised, open label controlled trial comparing safety and efficacy of pleural irrigation with normal saline versus intrapleural tissue plasminogen activator and DNase (fibrinolytic therapy) in pleural infection. BMC Pulm Med. 2026 Jan 21;26(1):74. doi: 10.1186/s12890-026-04125-1.
PubMed 41566445
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Open-Label Controlled Trial of Pleural Irrigation With Normal Saline Versus Intrapleural Tissue Plasminogen Activator and DNase (Fibrinolytic Therapy) in Pleural Infection.
- ClinicalTrials.gov ID
- NCT05903417
- Acronym / sponsor ID
- PENTAD-FT / JEP-2023-163
- Conditions
- Pleural Infection
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National University of MalaysiaUniversity, hospital or other
- Study start
- 10 Jul 2023 (actual)
- Primary completion
- 14 Oct 2025 (actual)
- Study completion
- 14 Oct 2025 (actual)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Parapneumonic effusions caused by an infection of the pleural membranes occur in 40-57% of cases of pneumonia. A variable percentage (10-20%) of parapneumonic effusions progresses to empyema (pus) and/or abscess formation (encapsulation). Pleural infection is associated with significant morbidity and mortality which may be as high as 20-35% in immunocompromised patients Standard treatment of these collections in adults involves antibiotic therapy, effective drainage of infected fluid and surgical intervention if conservative management fails. For parapneumonic effusions which require clearance, appropriate therapy is effective drainage via an intercostal catheter (ICC) with antibiotic therapy. The presence of fibrinous septae in the pleural space, known as loculations, may result in inadequate drainage of effusions and therefore non-resolution of infection and systemic sepsis. Without effective intercostal catheter drainage, surgical intervention (VATS or open) has usually been required to clear loculations for resolution of infection.
Non-surgical treatment options to reduce the impact of adhesions and locule include (in addition to appropriate antibiotic therapy) single and multiple thoracocentesis, or single and multiple intercostal tube thoracostomies, with or without intrapleural fibrinolytic agents.
Fibrinolytic agents including streptokinase, urokinase, alteplase and recombinant tissue plasminogen activator (rTPA) have been used safely and effectively intrapleurally for complicated pleural effusion and empyema.
MIST 2 trial has established intrapleural therapy as the mainstay of CPEE treatment hence avoiding surgery and decreasing the length of hospitalization; however, little is known about the correct dosage needed for tPA and DNase. Dose and duration of intrapleural therapy based on MIST 2 involve multiple dosing and can be time-consuming for health care providers . Previous studies showed that complexity of treatment is a factor associated with poor adherence to a regimen. For this reason, trying to find the minimum effective dose and simplifying the regimen is essential for minimizing side effects and maximizing adherence. The review of currently available literature shows concurrent administration of tPA and DNase to be safe and effective even at lower cumulative dose Other study was carried out in May 2022 in which Modified regimen intrapleural alteplase 16 mg t-PA with 5 mg DNase for total 3 doses that administered sequentially within 24 h had been used. In this study, modified regimen of t-PA and DNase offer an alternative therapeutic option for patients that are unfit or refuse surgical intervention but persistent pleural infection. They have demonstrated similar treatment success comparable to other studies, as evidenced by improvement on pleural fluid drainage and reduction in pleural opacity on day 7 chest x-ray was approximately 50% from the baseline using intrapleural 16 mg t-PA with 5 mg DNase. The mechanism of action of t-PA and DNase in pleural cavity remain unclear. Studies suggested that IPFT may trigger the monocyte chemoattractant protein 1 (MCP-1) pathway which promote pleural fluid formation and subsequently causes a therapeutic lavage effect that increases pleural fluid drainage.
Another option for intrapleural therapy may be pleural irrigation with normal saline. The idea behind is to dilute and remove bacteria, cytokines, inflammatory cells, and pro-fibrinogenic coagulation factors, which induce pleural fluid organization. Also, the mechanical process of irrigation increases pleural fluid drainage by reducing stasis and organization of the intrapleural contents .
A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care. Significantly fewer patients in the irrigation group were referred for surgery (30).
However, till date there is no study done on head to head comparison between intrapleural fibrinolytic with alteplase and DNAse Versus Pleural irrigationwith normal saline.
Detailed description
Problem Statement
Retained complicated pleural effusion is associated with a risk of empyema and sepsis.IPFT is commonly used as the bridging therapy to surgery. The efficacy of saline irrigation is not known. However, the probable problem in this study is when failed saline irrigation, the patient will be given IPFT as part of the intention to treat.
Research Questions:
- Is the combination of intrapleural Alteplase (t-PA) 5mg and DNase (Pulmozyme) 5mg superior than pleural pleural irrigation in the management of pleural infection?
Primary Objective:
- comparison of the safety outcome between IPFT and intrapleural saline irrigation, such as clinical deterioration, chest pain requiring escalation of analgesics, gastrointestinal bleeding, bleeding from chest drain site, intrapleural hemorrhage, hemoptysis, Hemoglobin (Hb) drop >10% from baseline requiring blood transfusion
Secondary Objectives:
- To determine the reduction of pleural opacity (in percentage) on chest radiograph from day 1 (randomization) to day 7
- To determine the change on inflammatory markers (WBC/CRP) from day 1 (randomization) to day 7
- To determine the outcome :
- Length of hospital stay (in days) after randomization for each group
- The need of surgical intervention in 30 days
- Mortality rate at 30 days
- To measure the volume of pleural effusion drainage (in mls) 48 hours following randomization
Study Hypothesis
- Subjects in the IPFT has more volume of pleural fluid drainage compared with pleural irrigation group
- Subjects in the IPFT has greater reduction of inflammatory parameters compared with pleural irrigation group
- Subjects in the IPFT has shorter length of hospital stay compared with pleural irrigation group
- Subjects in the IPFT has less surgical referral rate compared pleural irrigation group
- There is no difference of mortality rate between both groups
Subjects with pleural infection (complex parapneumonic effusion or empyema) with poor outflow ≤150cc pleural fluid from chest drain over 24 hours of insertion with standard medical therapy who are eligible for this study will be offered to participate into this study. Patient will be informed that this is an 'off label' drugs and a written informed consent will be obtained.
All patients will undergo chest tube/drain insertion. The decision to insert chest drain, the size of chest drain and when to initiate intrapleural t-PA/DNase is determined by the chest physician.
Ultrasound of thorax and chest radiograph will be performed within 24hours before randomization. Ultrasound of thorax is performed by chest physician with curve probe (ultrasound Mindray, model Z5) for confirmation of complex pleural effusions and chest tube's position. Complex pleural effusion on ultrasound is defined as fibrin strands or septa within the pleural effusion along with presence of loculations in pleural cavity. A baseline chest radiograph will be performed within 24 hours prior to intrapleural fibrinolysis or pleural irrigation to ensure the chest tube position.
Demographic data was collected prior to randomization, which consist of age,gender,ethnicity,BMI,comorbidities. Subjects will be randomized with a block of 4 (using sealed envelope) with random permutations of 2 groups : pleural irrigation group and intrapleural t-PA and DNase.
All patients that prescribed intrapleural t-PA/DNase during the study period will receive a standard dose of medications as below (Appendix 1).
Medication Regimen :
t-PA (Alteplase) 5mg and DNase (Pulmozyme)5mg t-PA (Alteplase) that is available in our pharmacy is 50mg ampoule and DNase (Pulmozyme) is 2.5mg per ampoule The number of installation of intrapleural t-PA/DNase depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5mg of Alteplase (t-PA) and 5mg DNase are diluted in each 50ml of 0.9% sodium chloride solution. t-PA and DNase are not mixed together in one syringe. The detailed method of t-PA/DNase therapy administration is described in Appendix 1. In brief , both medication are administered sequentially which t-PA is first instilled intrapleurally and the chest tube is then clamped for 45 minutes, then unclamped to allow free drainage for 45 minutes. The same procedure is then repeated for DNase. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement.
However, as for patients who were randomized into pleural irrigation group, subjects were administered 250 ml of 0.9% sodium chloride via chest tube a three way tap from a drip stand which were allowed drainage freely over 1 hour. Pleural irrigation will be performed minimum of 3 installations and maximum of 9 installation (3 times per day).
Both groups received standard care of treatment : which includes regular flushing of chest drain to maintain patency using 20mls of normal saline.
The primary outcome was to evaluate the volume of pleural effusion drainage (in mls) 72 hours following randomization. The volume drained measured after subtracting the amount of volume administered as per protocol.
The secondary outcome are measured by the change in the area of pleural opacity in chest x-ray (day 7 post t-PA/DNase compared to baseline), measured as the percentage of the ipsilateral hemithorax occupied by effusion. The area of pleural opacity and the area of the ipsilateral hemithorax will be measured digitally by two radiologists using Horos Project Software, v3.2.1 as described previously in Multicentre Intrapleural Sepsis Trial 2 (MIST-2)
Other outcomes that will be monitored include :
- Inflammatory markers including serum C-reactive protein (CRP) \& white blood count
- Length of hospital stay in days
- The need of surgical intervention within 30 days
- Adverse effects :
- Chest pain required escalation of analgesics
- Systemic bleeding
- Pleural bleeding
During any point of treatment subjects will be allowed to cross-over and analysis will be done as per intention to treat. Subjects in the pleural irrigation group may be switched to IPFT group if there is poor response to treatment (poor drainage of effusion), or adverse effects of irrigation as per clinician's judgement. On the contrary, subjects in the IPFT group may be switched to pleural irrigation group if patient developed any adverse effects of IPFT (e.g hemothorax,haemoptysis). Those who failed both treatment will be referred for surgical intervention
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pleural Irrigation Arm | Active comparator | Other: Saline irrigation with 250 mls normal saline (over 1 hour)subjects were administered 250 ml of 0.9% sodium chloride via chest tube a three way tap from a drip stand which were allowed drainage freely over 1 hour. Pleural irrigation will be performed minimum of 3 installations and maximum of 9 installation (3 times per day). |
| Intrapleural fibrinolytic arm | Active comparator | Drug: Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mgt-PA (Alteplase) 5mg and DNase (Pulmozyme)5mg t-PA (Alteplase) that is available in our pharmacy is 50mg ampoule and DNase (Pulmozyme) is 2.5mg per ampoule The number of installation of intrapleural t-PA/DNase depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5mg of Alteplase (t-PA) and 5mg DNase are diluted in each 50ml of 0.9% sodium. Both medication are administered sequentially which t-PA is first instilled intrapleurally and the chest tube is then clamped for 45 minutes, then unclamped to allow free drainage for 45 minutes. The same procedure is then repeated for DNase. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. Adult patient with aged ≥ 18 years old 2. Patients with pleural infection (complex parapneumonic effusion or empyema) with poor pleural fluid drainage of ≤ 150 ml after 24H of insertion of chest drain 3. Clinical features consistent with pleural infection ; fulfilling ≥ 2 of the following characteristics : i) Clinical evidence of infection such as fever and or elevated C-reactive protein (CRP) or total white blood count (TWBC) ii) Complex pleural effusion proven by thoracic ultrasound is defined as presence of fibrin strands or septations within pleural cavity iii) Pleural fluid that fulfil at least one of the characteristic :
- frank pus,
- exudative type of pleural effusion (according to light's criteria)
- gram stain or culture positive
- lactate dehydrogenase (LDH) > 900U/L
Key exclusion criteria (10 listed)
- Refusal to participate
- Known allergy to t-PA or DNase
- Acute stroke
- Significant bleeding diathesis/ active gastrointestinal bleed
- Major surgery in the previous 5 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mgThe number of installation of intrapleural t-PA/DNase depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5mg of Alteplase (t-PA) and 5mg DNase are diluted in each 50ml of 0.9% sodium chloride solution. t-PA and DNase are not mixed together in one syringe. In brief , both medication are administered sequentially which t-PA is first instilled intrapleurally and the chest tube is then clamped for 45 minutes, then unclamped to allow free drainage for 45 minutes. The same procedure is then repeated for DNase. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement. | Drug | Intrapleural fibrinolytic arm |
| Saline irrigation with 250 mls normal saline (over 1 hour)subjects were administered 250 ml of 0.9% sodium chloride via chest tube a three way tap from a drip stand which were allowed drainage freely over 1 hour. Pleural irrigation will be performed minimum of 3 installations and maximum of 9 installation (3 times per day). | Other | Pleural Irrigation Arm |
Primary outcome
to compare of the safety outcome between IPFT and intrapleural saline irrigation.
Time frame: Day 7
Number of participants who developed clinical deterioration, chest pain requiring escalation of analgesics, gastrointestinal bleeding, bleeding from chest drain site, intrapleural hemorrhage, hemoptysis, Hemoglobin (Hb) drop >10% from baseline requiring blood transfusion
5 secondary outcomes
To measure the change in the area of pleural opacity in chest x-ray compared to baseline
Time frame: Day 7
Changes in Inflammatory markers including serum C-reactive protein (CRP) & white blood count
Time frame: Day 7
Length of hospitalization
Time frame: through admission (up to 30 days)
the need for surgical referral
Time frame: throughout admission up to 30 days
to evaluate the volume of pleural effusion drainage (in mls) 72 hours following randomization.
Time frame: 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Derived from this study: PubMed 41566445Rozi SNM, Jailaini MFM, Azmel AA, Ismail NAN, Fuad NFN, Zainal IA, Ghan SL, Shah SA, Rahim MJC, Hamid MFA. A pilot randomised, open label controlled trial comparing safety and efficacy of pleural irrigation with normal saline versus intrapleural tissue plasminogen activator and DNase (fibrinolytic therapy) in pleural infection. BMC Pulm Med. 2026 Jan 21;26(1):74. doi: 10.1186/s12890-026-04125-1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohamed Faisal Abdul Hamid, MBBS (IIUM) principal investigator
National University of Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg and Saline irrigation with 250 mls normal saline (over 1 hour) in people with Pleural Infection, run by National University of Malaysia at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
to compare of the safety outcome between IPFT and intrapleural saline irrigation. (time frame: Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05903417, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.