Pleural InfectionALTON-PINCT07432373
Intrapleural Alteplase-Tyloxapol vs Intrapleural Alteplase-DNase in Pleural Infection
An observational study of Pleural Infection, run by National University of Malaysia at 1 site in Malaysia.
Trial summary
Pneumonia, thought to be the chief aetiological process in the development of pleural space infection, is defined as an infection of the lung parenchyma with an estimated annual incidence rate of 5-11 cases per 1000 population, with around 50,000 hospital admissions in the U.K. per year. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Infection
- What is being tested?
- Intrapleural t-PA/Dnase arm and t-PA (Alteplase) 5-10mg and Tyloxapol 200mg
- How many people
- 80 participants
- Where
- 1 siteMalaysia
- Study dates
- 1 Apr 2026to 1 Jul 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients with pleural infection (complex pleural effusion or empyema) with poor outflow (≤ 150 cc) from chest drain after 24 Hours of insertion in medical and non-medical wards from June 2023 to June 2025.
Who may be able to join
- Adult patient aged ≥ 18 years old
- Patients with pleural infection (complex parapneumonic effusion or empyema) with poor pleural fluid drainage of ≤ 150 ml after 24 hours of chest drain insertion received either t-PA-DNAse or t-PA/Tyloxapol.
- Clinical features consistent with pleural infection; fulfilling ≥ 2 of the following characteristics:
- 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 the presence of fibrin strands or septations within the pleural cavity iii) Pleural fluid that fulfils at least one of the characteristics:
- Frank Pus,
- Exudative type of pleural effusion (according to light's criteria)
Show all 10Show fewer
- Gram stain or culture positive
- Lactate dehydrogenase (LDH) > 900U/L
- Acidic with pH < 7.2
- Glucose level < 3.3 mmol/L
Who cannot join
- Incomplete data.
- Medical records that cannot be retrieved.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Malaysia1 site, 1 recruiting
- Recruiting
National University of Malaysia, Faculty of Medicine
Cheras, Kuala Lumpur, 56000
Mohamed Faisal Abdul Hamid, 0391455555, faisal.hamid@ppukm.ukm.edu.my
About this study
Official title: Comparative Analysis of Intrapleural Alteplase-Tyloxapol vs Intrapleural Alteplase-DNase in Pleural Infection (ALTON-PI)
Pneumonia, thought to be the chief aetiological process in the development of pleural space infection, is defined as an infection of the lung parenchyma with an estimated annual incidence rate of 5-11 cases per 1000 population, with around 50,000 hospital admissions in the U.K. per year. 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, adequate drainage of infected fluid, and surgical intervention if conservative management fails. Appropriate treatment is adequate drainage via an intercostal catheter (ICC) with antibiotic therapy for parapneumonic effusions requiring clearance. Frequently, simple ICC drainage is ineffective due to the presence of loculations, formed predominantly by fibrinous material deposited in the fibrinopurulent phase of empyema, preventing free drainage of infected pleural fluid. The presence of fibrinous septae in the pleural space, known as loculations, may result in inadequate drainage of effusions and, therefore, nonresolution of infection and systemic sepsis. Surgical intervention (VATS or open) is usually required to clear loculations and resolve infection without adequate intercostal catheter drainage.
Read more
Although the success rate of surgical intervention remains high, the morbidity and mortality of both VATS and open thoracotomy are of concern, particularly in a cohort of patients who may be older and with significant comorbidity. Less invasive therapies, which promote pleural space drainage and effective resolution of pleural infection, are therefore likely to be of considerable clinical utility.
The 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 Dornase Alfa/Deoxyribonuclease (DNase). Dose and duration of intrapleural therapy based on MIST 2 involve multiple dosing and can be time-consuming for health care providers. Nevertheless, treatment of pleural infection with fibrinolytic therapy has been incorporated in the British Thoracic Society guideline 2023.
Another study in 2022 by Cheong et al. used a modified regimen of intrapleural alteplase 16 mg t-PA with 5 mg DNase for three doses administered sequentially within 24 h. In this study, a modified regimen of t-PA and DNase offers an alternative therapeutic option for patients who are unfit or refuse surgical intervention but have persistent pleural infection. They have demonstrated similar treatment success comparable to other studies, as evidenced by improved pleural fluid drainage and reduced pleural opacity on day 7 chest x-ray, approximately 50% from the baseline. The mechanism of action of t-PA and DNase in the pleural cavity remains unclear. Studies suggested that IPFT may trigger the monocyte chemoattractant protein 1 (MCP-1) pathway, which promotes pleural fluid formation and subsequently causes a therapeutic lavage effect that increases pleural fluid drainage.
Read the detailed description
Research Questions:
- Is there a difference in efficacy and safety between a combination of intrapleural alteplase (5 mg + tacholiquin, with intrapleural alteplase 5mg and DNase (Pulmozyme) 5mg in managing pleural infection?
Primary Objective:
- To compare the reduction of pleural opacity (in percentage) on chest radiograph from baseline (0-24 hours pre-intervention) to day 7 post-intervention between group A (alteplase + DNase) and group B (alteplase + tacholiquin)
Secondary Objectives:
- To compare the absolute and percentage change in inflammatory markers (WBC/CRP) from baseline (0-24 hours pre-intervention) to day 7 between the two groups
- To compare the volume of pleural effusion drainage (in mL) 72 hours following post-intervention between the two groups
- To compare the outcome between the two groups:
- Length of hospital stay (in days) after the intervention for each group
- The need for surgical intervention within 30 days
- Adverse effects following alteplase/DNase and talteplase +Tacholiquin
- Mortality rate at 30 days
Study Hypothesis
- The mean reduction in pleural opacity (%) from baseline (0-24 h pre-intervention) to day 7 is the same in both groups.
- The mean change in WBC/CRP from baseline to day 7 is the same in both groups.
- The mean pleural effusion drainage volume in both groups over the first 72 hours post-intervention is the same.
- The mean length of hospital stay (days) post-intervention is the same in both groups.
- The proportion requiring surgical intervention within 30 days is the same in both groups.
- The proportion experiencing adverse effects is the same in both groups.
- The 30-day mortality proportion is the same in both groups.
Study Design Retrospective, observational cohort; on patients with pleural infection exposure defined by intrapleural regimen received (Alteplase+DNase vs Alteplase+Tyloxapol) DNase from June 2023 to June 2025 in HCTM UKM and University Malaya Medical Centre.
Study Population Adult patients with pleural infection (complex pleural effusion or empyema) with poor outflow (≤ 150 cc) from chest drain after 24 Hours of insertion in medical and non-medical wards, HCTM UKM, and UMMC from June 2023 to June 2025.
Sample Size and Power of Study Following the guidance of the UH Bristol and Weston Clinical Audit Team (Version 5), a pragmatic snapshot sample of 40 cases for each arm was deemed sufficient to measure current practice against the pre-defined standard, prioritizing feasibility over formal statistical representativeness.
- Conditions
- Pleural Infection
- Being tested
- Intrapleural t-PA/Dnase arm, t-PA (Alteplase) 5-10mg and Tyloxapol 200mg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrapleural t-PA/Dnase armDrug
t-PA (Alteplase) 5-10mg 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). 5-10mg 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.
t-PA (Alteplase) 5-10mg and Tyloxapol 200mgDrug
t-PA (Alteplase) that is available in our pharmacy is 50mg ampoule and Tyloxapol 200mg. The number of installation of intrapleural t-PA/Tyloxapol depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5-10mg of Alteplase (t-PA) and 200mg Tyloxapol 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 Tyloxapol. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement.
| Study group | Role | What they receive |
|---|---|---|
| Intrapleural t-PA/Dnase arm | t-PA (Alteplase) 5-10mg 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). 5-10mg 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 t-PA/Dnase arm | |
| Intrapleural t-PA/Tyloxapol | 5-10mg of Alteplase (t-PA) and 200mg Tyloxapol 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 Tyloxapol. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement. Receives: Drug: t-PA (Alteplase) 5-10mg and Tyloxapol 200mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Secondary outcomes (6)
Reduction in the level of serum C-reactive protein (CRP) from Day 1 to Day7 measured in mg/dL
reduction in CRP
Measured: Day 7
Reduction in the level of stotal white cell count from Day 1 to Day7 measured in 10x9/L
reduction in total white cell count
Measured: Day 7
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 medication volume instilled
Measured: 72 hours
Length of hospitalization
measured in days
Measured: throughout admission (up to 30 days)
the need for surgical referral
If failed intrapleural therapy (Discretion of treating physician)
Measured: throughout admission (up to 30 days)
to compare of the adverse effects between t-PA/Dnase and t-PA/Tyloxapol and intrapleural saline irrigation.
adverse effects 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
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study start1 Apr 2026
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)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
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University of Malaysia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Malaya
- Responsible party
- Sponsor
- Investigators
- Mohamed Faisal Abdul Hamid, MBBS(IIUM), Principal investigator, National University of Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07432373
- Sponsor's protocol ID
- FF-2026-033
- Acronym
- ALTON-PI
- Status last verified
- Jun 2026
- First submitted
- 19 Feb 2026
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mohamad Jailaini MF, Saini NA, Che Rahim MJ, Abdul Hamid MF. A potential prospect: The novel treatment of intrapleural saline irrigation with intrapleural tyloxapol in treating thoracic empyema. Respirol Case Rep. 2024 Aug 10;12(8):e70000. doi: 10.1002/rcr2.70000. eCollection 2024 Aug.
PubMed 39130089Scarci M, Abah U, Solli P, Page A, Waller D, van Schil P, Melfi F, Schmid RA, Athanassiadi K, Sousa Uva M, Cardillo G. EACTS expert consensus statement for surgical management of pleural empyema. Eur J Cardiothorac Surg. 2015 Nov;48(5):642-53. doi: 10.1093/ejcts/ezv272. Epub 2015 Aug 7.
PubMed 26254467Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740.
PubMed 21830966Thommi G, Shehan JC, Robison KL, Christensen M, Backemeyer LA, McLeay MT. A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions. Respir Med. 2012 May;106(5):716-23. doi: 10.1016/j.rmed.2012.02.005. Epub 2012 Mar 6.
PubMed 22398159Walker CA, Shirk MB, Tschampel MM, Visconti JA. Intrapleural alteplase in a patient with complicated pleural effusion. Ann Pharmacother. 2003 Mar;37(3):376-9. doi: 10.1345/aph.1C248.
PubMed 12639166Majid A, Kheir F, Folch A, Fernandez-Bussy S, Chatterji S, Maskey A, Fashjian M, Cheng G, Ochoa S, Alape D, Folch E. Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience. Ann Am Thorac Soc. 2016 Sep;13(9):1512-8. doi: 10.1513/AnnalsATS.201602-127OC.
PubMed 27333122Cheong 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.
PubMed 35581627Provan JL. The management of postpneumonectomy empyema. J Thorac Cardiovasc Surg. 1971 Jan;61(1):107-9. No abstract available.
PubMed 5540449
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Analysis of Intrapleural Alteplase-Tyloxapol vs Intrapleural Alteplase-DNase in Pleural Infection (ALTON-PI)
- ClinicalTrials.gov ID
- NCT07432373
- Acronym / sponsor ID
- ALTON-PI / FF-2026-033
- Conditions
- Pleural Infection
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National University of MalaysiaUniversity, hospital or other
- Collaborators
- University of Malaya
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 25 Feb 2026 (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.
Pneumonia, thought to be the chief aetiological process in the development of pleural space infection, is defined as an infection of the lung parenchyma with an estimated annual incidence rate of 5-11 cases per 1000 population, with around 50,000 hospital admissions in the U.K. per year. 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, adequate drainage of infected fluid, and surgical intervention if conservative management fails. Appropriate treatment is adequate drainage via an intercostal catheter (ICC) with antibiotic therapy for parapneumonic effusions requiring clearance. Frequently, simple ICC drainage is ineffective due to the presence of loculations, formed predominantly by fibrinous material deposited in the fibrinopurulent phase of empyema, preventing free drainage of infected pleural fluid. The presence of fibrinous septae in the pleural space, known as loculations, may result in inadequate drainage of effusions and, therefore, nonresolution of infection and systemic sepsis. Surgical intervention (VATS or open) is usually required to clear loculations and resolve infection without adequate intercostal catheter drainage.
Although the success rate of surgical intervention remains high, the morbidity and mortality of both VATS and open thoracotomy are of concern, particularly in a cohort of patients who may be older and with significant comorbidity. Less invasive therapies, which promote pleural space drainage and effective resolution of pleural infection, are therefore likely to be of considerable clinical utility.
The 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 Dornase Alfa/Deoxyribonuclease (DNase). Dose and duration of intrapleural therapy based on MIST 2 involve multiple dosing and can be time-consuming for health care providers. Nevertheless, treatment of pleural infection with fibrinolytic therapy has been incorporated in the British Thoracic Society guideline 2023.
Another study in 2022 by Cheong et al. used a modified regimen of intrapleural alteplase 16 mg t-PA with 5 mg DNase for three doses administered sequentially within 24 h. In this study, a modified regimen of t-PA and DNase offers an alternative therapeutic option for patients who are unfit or refuse surgical intervention but have persistent pleural infection. They have demonstrated similar treatment success comparable to other studies, as evidenced by improved pleural fluid drainage and reduced pleural opacity on day 7 chest x-ray, approximately 50% from the baseline. The mechanism of action of t-PA and DNase in the pleural cavity remains unclear. Studies suggested that IPFT may trigger the monocyte chemoattractant protein 1 (MCP-1) pathway, which promotes pleural fluid formation and subsequently causes a therapeutic lavage effect that increases pleural fluid drainage.
Detailed description
Research Questions:
- Is there a difference in efficacy and safety between a combination of intrapleural alteplase (5 mg + tacholiquin, with intrapleural alteplase 5mg and DNase (Pulmozyme) 5mg in managing pleural infection?
Primary Objective:
- To compare the reduction of pleural opacity (in percentage) on chest radiograph from baseline (0-24 hours pre-intervention) to day 7 post-intervention between group A (alteplase + DNase) and group B (alteplase + tacholiquin)
Secondary Objectives:
- To compare the absolute and percentage change in inflammatory markers (WBC/CRP) from baseline (0-24 hours pre-intervention) to day 7 between the two groups
- To compare the volume of pleural effusion drainage (in mL) 72 hours following post-intervention between the two groups
- To compare the outcome between the two groups:
- Length of hospital stay (in days) after the intervention for each group
- The need for surgical intervention within 30 days
- Adverse effects following alteplase/DNase and talteplase +Tacholiquin
- Mortality rate at 30 days
Study Hypothesis
- The mean reduction in pleural opacity (%) from baseline (0-24 h pre-intervention) to day 7 is the same in both groups.
- The mean change in WBC/CRP from baseline to day 7 is the same in both groups.
- The mean pleural effusion drainage volume in both groups over the first 72 hours post-intervention is the same.
- The mean length of hospital stay (days) post-intervention is the same in both groups.
- The proportion requiring surgical intervention within 30 days is the same in both groups.
- The proportion experiencing adverse effects is the same in both groups.
- The 30-day mortality proportion is the same in both groups.
Study Design Retrospective, observational cohort; on patients with pleural infection exposure defined by intrapleural regimen received (Alteplase+DNase vs Alteplase+Tyloxapol) DNase from June 2023 to June 2025 in HCTM UKM and University Malaya Medical Centre.
Study Population Adult patients with pleural infection (complex pleural effusion or empyema) with poor outflow (≤ 150 cc) from chest drain after 24 Hours of insertion in medical and non-medical wards, HCTM UKM, and UMMC from June 2023 to June 2025.
Sample Size and Power of Study Following the guidance of the UH Bristol and Weston Clinical Audit Team (Version 5), a pragmatic snapshot sample of 40 cases for each arm was deemed sufficient to measure current practice against the pre-defined standard, prioritizing feasibility over formal statistical representativeness.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intrapleural t-PA/Dnase arm | – | Drug: Intrapleural t-PA/Dnase armt-PA (Alteplase) 5-10mg 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). 5-10mg 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. |
| Intrapleural t-PA/Tyloxapol | – | Drug: t-PA (Alteplase) 5-10mg and Tyloxapol 200mg5-10mg of Alteplase (t-PA) and 200mg Tyloxapol 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 Tyloxapol. 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
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with pleural infection (complex pleural effusion or empyema) with poor outflow (≤ 150 cc) from chest drain after 24 Hours of insertion in medical and non-medical wards from June 2023 to June 2025.
Key inclusion criteria (10 listed)
- Adult patient aged ≥ 18 years old
- Patients with pleural infection (complex parapneumonic effusion or empyema) with poor pleural fluid drainage of ≤ 150 ml after 24 hours of chest drain insertion received either t-PA-DNAse or t-PA/Tyloxapol.
- Clinical features consistent with pleural infection; fulfilling ≥ 2 of the following characteristics:
Key exclusion criteria (2 listed)
- Incomplete data.
- Medical records that cannot be retrieved.
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 t-PA/Dnase armt-PA (Alteplase) 5-10mg 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). 5-10mg 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. | Drug | Intrapleural t-PA/Dnase arm |
| t-PA (Alteplase) 5-10mg and Tyloxapol 200mgt-PA (Alteplase) that is available in our pharmacy is 50mg ampoule and Tyloxapol 200mg. The number of installation of intrapleural t-PA/Tyloxapol depends on the discretion of the treating physician (at least 6 hours apart between each dose). 5-10mg of Alteplase (t-PA) and 200mg Tyloxapol 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 Tyloxapol. Selection of the timing of treatment and removal of chest tube are depending on the chest physician's judgement. | Drug | Intrapleural t-PA/Tyloxapol |
Primary outcome
To measure the change in the area of pleural opacity in chest x-ray compared to baseline
Time frame: Day 7
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)
6 secondary outcomes
Reduction in the level of serum C-reactive protein (CRP) from Day 1 to Day7 measured in mg/dL
Time frame: Day 7
Reduction in the level of stotal white cell count from Day 1 to Day7 measured in 10x9/L
Time frame: Day 7
to evaluate the volume of pleural effusion drainage (in mls) 72 hours following randomization
Time frame: 72 hours
Length of hospitalization
Time frame: throughout admission (up to 30 days)
the need for surgical referral
Time frame: throughout admission (up to 30 days)
to compare of the adverse effects between t-PA/Dnase and t-PA/Tyloxapol and intrapleural saline irrigation.
Time frame: Day 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
- Background: PubMed 39130089Mohamad Jailaini MF, Saini NA, Che Rahim MJ, Abdul Hamid MF. A potential prospect: The novel treatment of intrapleural saline irrigation with intrapleural tyloxapol in treating thoracic empyema. Respirol Case Rep. 2024 Aug 10;12(8):e70000. doi: 10.1002/rcr2.70000. eCollection 2024 Aug.
- Results publication: PubMed 26254467Scarci M, Abah U, Solli P, Page A, Waller D, van Schil P, Melfi F, Schmid RA, Athanassiadi K, Sousa Uva M, Cardillo G. EACTS expert consensus statement for surgical management of pleural empyema. Eur J Cardiothorac Surg. 2015 Nov;48(5):642-53. doi: 10.1093/ejcts/ezv272. Epub 2015 Aug 7.
- Results publication: PubMed 21830966Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740.
- Results publication: PubMed 22398159Thommi G, Shehan JC, Robison KL, Christensen M, Backemeyer LA, McLeay MT. A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions. Respir Med. 2012 May;106(5):716-23. doi: 10.1016/j.rmed.2012.02.005. Epub 2012 Mar 6.
- Results publication: PubMed 12639166Walker CA, Shirk MB, Tschampel MM, Visconti JA. Intrapleural alteplase in a patient with complicated pleural effusion. Ann Pharmacother. 2003 Mar;37(3):376-9. doi: 10.1345/aph.1C248.
- Results publication: PubMed 27333122Majid A, Kheir F, Folch A, Fernandez-Bussy S, Chatterji S, Maskey A, Fashjian M, Cheng G, Ochoa S, Alape D, Folch E. Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience. Ann Am Thorac Soc. 2016 Sep;13(9):1512-8. doi: 10.1513/AnnalsATS.201602-127OC.
- Results publication: PubMed 35581627Cheong 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.
- Results publication: PubMed 5540449Provan JL. The management of postpneumonectomy empyema. J Thorac Cardiovasc Surg. 1971 Jan;61(1):107-9. No abstract available.
- 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.
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?
An observational study of 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 10 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 30 Jun 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamed Faisal Abdul Hamid, MBBS(IIUM) (0391455555, faisal.hamid@hctm.ukm.edu.my), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure the change in the area of pleural opacity in chest x-ray compared to baseline (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 NCT07432373, which also lists 8 linked publications.
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 30 Jun 2026.