Trial of Reduced Alteplase Dose for Parapneumonic Effusion (TRAPPE)

NCT05766124 | Recruiting Phase 2

• 1 other identifier: TRAPPE
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Objectives: A pilot study to assess the feasibility of a randomization trial protocol comparing low (2.5mg) and standard (10mg) doses of intrapleural tissue plasminogen activator (tPA) with deoxyribonucleases (DNase) in unresolved pleural infection. Hypothesis: The proposed randomized protocol comparing low dose and standard doses of intrapleural tPA (with DNase) therapy will be feasible and acceptable. Design and subjects: A single-center, two-arm, double-blinded, randomized controlled feasibility study which includes subjects with unresolved pleural infection eligible for intrapleural tPA/DNase injection, with follow-ups till 3 months after hospital discharge. Interventions: Recruited subjects will be randomized in 1:1 ratio to receive a maximum of 6 doses of intrapleural tPA (with DNase) starting at either 2.5mg or 10mg. A clinical decision is allowed at or after the third dose of tPA to continue with the assigned regimen (blinded) or convert to open-label use of 10mg doses of tPA to complete the course based on the clinical response. Main outcome measures: The main outcome is the feasibility of the trial protocol, based on the percentage of eligible patients enrolled, retained to discharge, and completing 3 months of follow-up. Other important outcomes include survival at 3 months follow-up and without the need for surgical intervention, the need for additional pleural interventions, the number of decisions to convert to open-labelled use of 10mg intrapleural tPA, clinical and radiographic response after the treatment course, safety profiles, especially bleeding complications and the number and reason for protocol violation. Data analysis and expected results: Feasibility outcomes will be reported as descriptive data. Comparison of outcomes between the two treatment groups will be analyzed on an intention-to-treat basis. Safety outcomes will be reported descriptively for each group. The reported estimates of recruitment rates, adherence, follow-up completeness, and variability and event rates for key clinical and bleeding outcomes will be used, to inform the design and sample size considerations future studies incorporating the current study design

Conditions

Pleural Infection

Outcome Measures

Primary Outcomes (1)

• Study feasibility

  Study feasibility based on \>50% of eligible patients being successfully randomized, \>95% of randomized participants retained to discharge, and \>80% of randomized participants

  90 days

Secondary Outcomes (14)

• Treatment success

  90 days

• need for additional pleural interventions

  90 days

• Open use of intrapleural 10mg tPA

  3 days

• Bleeding events

  90 days

• Time to clinical stability

  90 days

Study Arms (2)

Low dose tPA

EXPERIMENTAL

Patients with pleural infection and will receive a starting dose of tPA at 2.5mg

Drug: Tissue Plasminogen Activator

Standard dose tPA

ACTIVE COMPARATOR

Patients with pleural infection and will receive a starting dose of tPA at 10mg

Drug: Tissue Plasminogen Activator

Interventions

Tissue Plasminogen Activator DRUG

Intrapleural administration of tissue plasminogen activator

Also known as: Alteplase

Low dose tPA; Standard dose tPA

Eligibility Criteria

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

You may qualify if:

• Clinical features suggesting uncontrolled pleural infection with incomplete drainage of pleural effusion, at least 1 day after insertion of pleural drain (French size 12 or above) and administration of antibiotics.
• Intend to administer intrapleural fibrinolytic
• Written informed consent obtained

You may not qualify if:

• Previously received intrapleural tPA to the ipsilateral pleural space for the current episode of pleural infection.
• Known sensitivity to tPA or DNase.
• A coincidental stroke, major haemorrhage or major trauma.
• Frank bleeding or evidence of puncture to the intercostal artery during chest drain insertion.
• Ongoing frank bleeding from the ipsilateral pleural space.
• Has had puncture of a non-compressible vessel in the previous 14 days.
• Has had major surgery in the previous 14 days.
• Has had unprovoked gastrointestinal bleeding or intracranial haemorrhage in the last 3 months.
• Active use of anticoagulation (except prophylaxis for deep vein thrombosis) or dual-antiplatelet agents.
• Active use of any systemic fibrinolytic therapy or any airway DNase therapy.
• On long-term macrolide antibiotics (as they may interact with DNase).
• Uncorrectable bleeding diathesis or baseline INR \> 1.5.
• Has had a previous pneumonectomy (either on the same or contralateral side).
• Presence of active bronchopleural fistula.
• Age less than 18 years old.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (2)

Chinese University of Hong Kong

Hong Kong, Hong Kong, Hong Kong

RECRUITING

Prince of Wales Hospital

Hong Kong, Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Interventions

Tissue Plasminogen Activator

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

• David SC Hui, MD

  Chinese University of Hong Kong

  STUDY DIRECTOR

Central Study Contacts

Ka Pang Chan, MBChB

CONTACT

35052211; chankapang@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The research team, clinicians, nursing staff, and patients will be blinded to the treatment arm. A copy of the randomisation code will be held only by a research team member performing randomisation. Access to this code for a patient before the completion of the trial, will only be permitted in exceptional circumstances, such as being necessary to determine the best acute medical care for a patient, and only after discussion with the Principal Investigator (PI) or his deputy. Pharmacy staff will receive unblinded randomisation information in order to prepare the study drug of assigned doses. The labelling of the blinded drugs will be under the supervision of a dedicated pharmacy. Each course of trial treatments will be pre-prepared in a trial numbered pack and dispensed to the ward at randomisation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Lecturer

Model Details: Recruited subjects will be randomized in 1:1 ratio to receive a course of maximum of 6 doses intrapleural tPA (Actilyse®, 50mg ampoule, Boehringer Ingelheim) with starting dose at either low dose (2.5mg) or standard dose (10mg) in addition to fixed dose deoxyribonuclease. The first dose of intrapleural tPA will be given at the time of randomization. At or after the third dose of tPA, the attending physician will be allowed to continue with the assigned dose of tPA or escalate to 10mg tPA for the remaining doses based on the clinical response, without knowing the previous doses and not breaking the blinding. This study will follow patients through their hospital stay and at outpatient visits at 30 and 90 days.

Study Record Dates

• First Submitted: February 25, 2023
• First Posted: March 13, 2023
• Study Start: November 1, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (2)