Efficacy and Safety of Intrapleural Fibrinolytic Therapy in Tuberculous Pleural Effusion Versus Non-Tuberculous Pleural Infection

NCT07823075 | Not Yet Recruiting DMC

• 1 other identifier: FF-2026-296
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective cohort study evaluates the efficacy and safety of intrapleural fibrinolytic therapy (tPA/DNase) in patients with tuberculous pleural effusion compared with non-tuberculous pleural infection at Hospital Canselor Tuanku Muhriz (HCTM), Malaysia. The study aims to compare radiological improvement, clinical outcomes, and treatment-related adverse events to provide evidence supporting the use of IPFT in tuberculous pleural effusion.

Conditions

Tuberculous Pleural Effusion

Keywords

Tuberculous Pleural Effusion; Non-Tuberculous Pleural Infection; Intrapleural Fibrinolytic Therapy; Tissue Plasminogen Activator; Alteplase; DNase

Outcome Measures

Primary Outcomes (1)

• Percentage reduction in pleural opacity area on chest radiograph following IPFT

  Radiological response to IPFT will be assessed by measuring the percentage reduction in pleural opacity area on chest radiographs from baseline (Day 0, prior to IPFT initiation) to the follow-up radiograph performed between Day 7-10 after IPFT initiation or the earliest available follow-up radiograph, whichever occurs earlier. Pleural opacity area will be measured using Horos software version 3.3.2.

  Day 0 (before initiation of IPFT) to Day 7-10 after initiation of IPFT

Secondary Outcomes (3)

• Clinical characteristics of participants with TPE and non-TPE

  From diagnosis until completion of the index hospital admission

• Clinical treatment success following IPFT

  Day 0 (before IPFT initiation) to Day 7-10 after IPFT initiation or until hospital discharge, with surgical intervention assessed within 30 days after IPFT initiation

• Treatment-related adverse events following IPFT in patients with TPE

  From initiation of IPFT until hospital discharge or within 30 days after IPFT initiation

Study Arms (2)

Non- Tuberculous Pleural Effusion

Non-TPE: Patients with pleural infection who had no microbiological or histological evidence of MTB and/or for whom an alternative diagnosis was established.

Procedure: Intrapleural Fibrinolytic Therapy (IPFT)

Tuberculous Pleural effusion

Definite TPE - Patients with microbiologically confirmed TB from pleural fluid or pleural biopsy specimens (positive MTB culture, AFB smear, or Xpert MTB), and/or histopathological evidence of caseating granulomatous inflammation consistent with TB on pleural biopsy. OR Clinical TPE - Patients without microbiological or histopathological confirmation but diagnosed by a respiratory physician based on clinical, radiological, biochemical, and/or pleuroscopic findings. Diagnosis requires at least two supportive criteria: compatible TB symptoms, radiological features suggestive of pleural TB, pleural fluid ADA \>40 U/L, pleuroscopy findings suggestive of tuberculous pleuritis (e.g., pleural nodularity, inflammation, thickening, adhesions, or granulomatous changes), and/or clinical or radiological improvement following empirical anti-tuberculosis therapy.

Procedure: Intrapleural Fibrinolytic Therapy (IPFT)

Interventions

Intrapleural Fibrinolytic Therapy (IPFT) PROCEDURE

Patients received intrapleural fibrinolytic therapy with alteplase and DNase through an intercostal chest tube for management of complicated pleural infection. Clinical outcomes following IPFT were compared between patients with tuberculous pleural effusion and non-tuberculous pleural effusion.

Also known as: Alteplase (tissue plasminogen activator, tPA), Dornase alfa (DNase)

Non- Tuberculous Pleural Effusion; Tuberculous Pleural effusion

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All adult patients diagnosed with tuberculous pleural effusion and non-tuberculous pleural effusion who received IPFT using tissue plasminogen activator and deoxyribonuclease, during the study period. Relevant data will be extracted from patients' case notes or electronic medical records.

You may qualify if:

• Adults aged ≥18 years.
• Patients with tuberculous pleural effusion or non-tuberculous pleural effusion diagnosed based on clinical, radiological, laboratory, microbiological, histopathological, and/or pleuroscopic findings.
• Patients who received intrapleural fibrinolytic therapy with tissue plasminogen activator and deoxyribonuclease during the study period.

You may not qualify if:

• Malignant and transudative pleural effusion
• Patients who received intrapleural fibrinolytic therapy as monotherapy with either tissue plasminogen activator or deoxyribonuclease alone.
• Incomplete medical records

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (1)

National University of Malaysia

Kuala Lumpur, Kuala Lumpur, 56000, Malaysia

Location

Related Publications (13)

• Colares PFB, Rivas JKD, Sciortino ADS, Sales RKB, Teixeira LR. Tuberculous empyema: combined intrapleural therapy might be an alternative. J Bras Pneumol. 2022 Nov 28;48(6):e20220232. doi: 10.36416/1806-3756/e20220232. No abstract available.

  PMID: 36449818 RESULT

• Zhai K, Lu Y, Shi HZ. Tuberculous pleural effusion. J Thorac Dis. 2016 Jul;8(7):E486-94. doi: 10.21037/jtd.2016.05.87.

  PMID: 27499981 RESULT

• Abdul Hamid MF, Hasbullah AHH, Mohamad Jailaini MF, Nik Abeed NN, Ng BH, Haron H, Md Ali NA, Ismail MI, Nik Ismail NA, Abdul Rahman MR, Ban AY. Retrospective review comparing intrapleural fibrinolytic therapy (alteplase) and surgical intervention in complex pleural effusion. BMC Pulm Med. 2022 Nov 23;22(1):439. doi: 10.1186/s12890-022-02239-w.

  PMID: 36419155 RESULT

• Yong GKW, Wong JJJ, Zhang X, Tan CPS, Wang XN, Quek PS, Yap KH. Intrapleural fibrinolytic therapy for pleural infections: Outcomes from a cohort study. Ann Acad Med Singap. 2024 Dec 12;53(12):724-733. doi: 10.47102/annals-acadmedsg.2024276.

  PMID: 39748171 RESULT

• McNally E, Ross C, Gleeson LE. The tuberculous pleural effusion. Breathe (Sheff). 2023 Dec;19(4):230143. doi: 10.1183/20734735.0143-2023. Epub 2023 Dec 19.

  PMID: 38125799 RESULT

• Bian Y, Deng M, Zhang Q, Hou G. Global trends of research on tuberculous pleurisy over the past 15 years: A bibliometric analysis. Front Cell Infect Microbiol. 2022 Aug 30;12:937811. doi: 10.3389/fcimb.2022.937811. eCollection 2022.

  PMID: 36111237 RESULT

• Chiner E, Nomdedeu M, Vanes S, Pastor E, Esteban V, Castello C, Boira I, Molina V, Arriero JM, Sancho-Chust JN. Clinical and Epidemiological Features of Tuberculous Pleural Effusion in Alicante, Spain. J Clin Med. 2021 Sep 26;10(19):4392. doi: 10.3390/jcm10194392.

  PMID: 34640410 RESULT

• Lo Cascio CM, Kaul V, Dhooria S, Agrawal A, Chaddha U. Diagnosis of tuberculous pleural effusions: A review. Respir Med. 2021 Nov;188:106607. doi: 10.1016/j.rmed.2021.106607. Epub 2021 Sep 6.

  PMID: 34536698 RESULT

• Shien TK, Mohamad Jailaini MF, Azmel AA, Munusamy V, Alaga A, Abdul Hamid MF. Diagnostic utility of pleural fluid adenosine deaminase in tuberculous pleural effusion in patients with exudative effusion: a retrospective multicenter study (ADATPE). J Thorac Dis. 2026 Mar 31;18(3):216. doi: 10.21037/jtd-2026-1-0015. Epub 2026 Feb 27.

  PMID: 41988261 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

• Cheong XK, Abdul Hamid MF. Intrapleural alteplase and DNase for complex tuberculous pleurisy: a medical approach. Respirol Case Rep. 2021 Jan 3;9(2):e00706. doi: 10.1002/rcr2.706. eCollection 2021 Feb.

  PMID: 33425359 RESULT

• Luengo-Fernandez R, Penz E, Dobson M, Psallidas I, Nunn AJ, Maskell NA, Rahman NM. Cost-effectiveness of intrapleural use of tissue plasminogen activator and DNase in pleural infection: evidence from the MIST2 randomised controlled trial. Eur Respir J. 2019 Aug 1;54(2):1801550. doi: 10.1183/13993003.01550-2018. Print 2019 Aug.

  PMID: 31097519 RESULT

• Piccolo F, Popowicz N, Wong D, Lee YC. Intrapleural tissue plasminogen activator and deoxyribonuclease therapy for pleural infection. J Thorac Dis. 2015 Jun;7(6):999-1008. doi: 10.3978/j.issn.2072-1439.2015.01.30.

  PMID: 26150913 RESULT

MeSH Terms

Interventions

Tissue Plasminogen Activator; dornase alfa

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

  National University of Malaysia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamed Faisal Abdul Hamid, MBBS

CONTACT

60391455555; faisal.hamid@hctm.ukm.edu.my

VINOD RAJ MANIKAM, MD

CONTACT

60391455555; veenod18@gmail.com

Study Design

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

Study Record Dates

• First Submitted: August 2, 2026
• First Posted: September 16, 2026
• Study Start: September 20, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)