Intrapleural Alteplase-Tyloxapol vs Intrapleural Alteplase-DNase in Pleural Infection

NCT07432373 | Recruiting

• 1 other identifier: FF-2026-033
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pleural Infection

Outcome Measures

Primary Outcomes (1)

• 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)

  Day 7

Secondary Outcomes (6)

• Reduction in the level of serum C-reactive protein (CRP) from Day 1 to Day7 measured in mg/dL

  Day 7

• Reduction in the level of stotal white cell count from Day 1 to Day7 measured in 10x9/L

  Day 7

• to evaluate the volume of pleural effusion drainage (in mls) 72 hours following randomization

  72 hours

• Length of hospitalization

  throughout admission (up to 30 days)

• the need for surgical referral

  throughout admission (up to 30 days)

Study Arms (2)

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.

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.

Drug: t-PA (Alteplase) 5-10mg and Tyloxapol 200mg

Interventions

Intrapleural t-PA/Dnase arm DRUG

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.

Intrapleural t-PA/Dnase arm

t-PA (Alteplase) 5-10mg and Tyloxapol 200mg DRUG

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.

Intrapleural t-PA/Tyloxapol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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:
• 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 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)
• Gram stain or culture positive
• Lactate dehydrogenase (LDH) \> 900U/L
• Acidic with pH \< 7.2
• Glucose level \< 3.3 mmol/L

You may not qualify if:

• Incomplete data.
• Medical records that cannot be retrieved.

Sponsors & Collaborators

• National University of Malaysia: lead
• University of Malaya: collaborator

Study Sites (1)

National University of Malaysia, Faculty of Medicine

Cheras, Kuala Lumpur, 56000, Malaysia

RECRUITING

Related Publications (8)

• 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.

  PMID: 39130089 BACKGROUND

• Scarci 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.

  PMID: 26254467 RESULT

• Rahman 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.

  PMID: 21830966 RESULT

• Thommi 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.

  PMID: 22398159 RESULT

• Walker 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.

  PMID: 12639166 RESULT

• Majid 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.

  PMID: 27333122 RESULT

• 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.

  PMID: 35581627 RESULT

• Provan JL. The management of postpneumonectomy empyema. J Thorac Cardiovasc Surg. 1971 Jan;61(1):107-9. No abstract available.

  PMID: 5540449 RESULT

MeSH Terms

Interventions

Tissue Plasminogen Activator; tyloxapol

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Mohamed Faisal Abdul Hamid, MBBS(IIUM)

  National University of Malaysia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamed Faisal Abdul Hamid, MBBS(IIUM)

CONTACT

0391455555; faisal.hamid@hctm.ukm.edu.my

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: February 25, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)