Alteplase dose assessment for pleural infection therapy (ADAPT) study-2: Use of 2.5 mg alteplase as a starting intrapleural dose

Document Type

Journal Article

Publication Title

Respirology

Volume

27

Issue

7

First Page

510

Last Page

516

PubMed ID

35441458

Publisher

Wiley

School

School of Medical and Health Sciences

RAS ID

51786

Funders

Medical Research Future Fund

Comments

Popowicz, N., Ip, H., Lau, E. P., Piccolo, F., Dootson, K., Yeoh, C., ... & Lee, Y. G. (2022). A lteplase D ose A ssessment for P leural infection T herapy (ADAPT) Study‐2: Use of 2.5 mg alteplase as a starting intrapleural dose. Respirology, 27(7), p.510-516. https://doi.org/10.1111/resp.14261

Abstract

Background and objective: Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) therapy is increasingly used in pleural infection. Bleeding risks and costs associated with tPA remain the clinical concerns. Our dose de-escalation series aims to establish the lowest effective dosing regimen for tPA/DNase. This study assesses the intrapleural use of 2.5 mg tPA/5 mg DNase for pleural infection. Methods: Consecutive patients with pleural infection treated with a starting regime of 2.5 mg tPA/5 mg DNase were included from two centres in Australia and UK. Escalation of tPA dose was permitted if clinical response was inadequate. Results: Sixty-nine patients (mean age 61.0 years) received intrapleural 2.5 mg tPA/5 mg DNase. Most (88.4%) were treated successfully and discharged from hospital without surgery by 90 days. Patients received a median of 5 [interquartile range [IQR] = 3–6] doses of tPA/DNase. Total amount of tPA used per patient was 12.5 mg [median, IQR = 7.5–15.0]. Seventeen patients required dose escalation of tPA; most (n = 12) for attempted drainage of distant non-communicating locule(s). Treatment success was corroborated by clearance of pleural opacities on radiographs (from median 27.0% [IQR = 17.1–44.5] to 11.0% [IQR = 6.4–23.3] of hemithorax, p < 0.0001), increased pleural fluid drainage (1.98 L [median, IQR = 1.38–2.68] over 72 h following commencement of tPA/DNase) and reduction of serum C-reactive protein level (by 45.0% [IQR = 39.3–77.0] from baseline at day 5, p < 0.0001). Two patients required surgery. Six patients with significant comorbidities (e.g., advanced cancer) had ongoing infection when palliated and died. Two patients experienced self-limiting pleural bleeding and received blood transfusion. Conclusion: A starting intrapleural regime of 2.5 mg tPA/5 mg DNase, with up-titration if needed, can be effective and deserves further exploration.

DOI

10.1111/resp.14261

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