Pleural Irrigation With Normal Saline Versus Intrapleural Fibrinolytic

NCT05903417 | Completed

• 1 other identifier: JEP-2023-163
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Pleural Infection

Outcome Measures

Primary Outcomes (1)

• 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

  Day 7

Secondary Outcomes (5)

• To measure the change in the area of pleural opacity in chest x-ray compared to baseline

  Day 7

• Changes in Inflammatory markers including serum C-reactive protein (CRP) & white blood count

  Day 7

• Length of hospitalization

  through admission (up to 30 days)

• the need for surgical referral

  throughout admission up to 30 days

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

  72 hours

Study Arms (2)

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).

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.

Drug: Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg

Interventions

Intrapleural fibrinolytic with alteplase 5mg and pulmozyme 5 mg DRUG

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.

Intrapleural fibrinolytic arm

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).

Pleural Irrigation Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• 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
• Bronchopleural fistula
• Pregnancy
• Coagulapathy (INR \> 2, APTT \> 100)
• Platelet count \< 50000 cells

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (1)

National University of Malaysia

Kuala Lumpur, Kuala Lumpur, 56000, Malaysia

Location

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 (IIUM)

  National University of Malaysia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 15, 2023
• Study Start: July 10, 2023
• Primary Completion: October 14, 2025
• Study Completion: October 14, 2025
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)