Intrapleural Dornase and Tissue Plasminogen Activator in pediatric empyema (DTPA): a study protocol for a randomized controlled trial

Michael H Livingston, Sanjay Mahant, Felix Ratjen, Bairbre L Connolly, Kevin Thorpe, Muhammad Mamdani, Ian Maclusky, Sophie Laberge, Lucy Giglia, J Mark Walton, Connie L Yang, Ashley Roberts, Anna C Shawyer, Mary Brindle, Simon J Parsons, Cristina A Stoian, Eyal Cohen, Michael H Livingston, Sanjay Mahant, Felix Ratjen, Bairbre L Connolly, Kevin Thorpe, Muhammad Mamdani, Ian Maclusky, Sophie Laberge, Lucy Giglia, J Mark Walton, Connie L Yang, Ashley Roberts, Anna C Shawyer, Mary Brindle, Simon J Parsons, Cristina A Stoian, Eyal Cohen

Abstract

Background: A randomized controlled trial of adults with empyema recently demonstrated decreased length of stay in hospital in patients treated with intrapleurally administered dornase alfa and fibrinolytics compared to fibrinolytics alone. Whether this treatment strategy is safe and effective in children remains unknown.

Methods/design: This study protocol is for a superiority, placebo-controlled, parallel-design, multicenter randomized controlled trial. The participants are previously well children admitted to a children's hospital with a diagnosis of empyema requiring chest tube insertion and fibrinolytics administered intrapleurally. Children will be randomized after the treating physician has decided that pleural drainage is required but prior to chest tube insertion. After chest tube insertion, participants in the treatment group will receive intrapleurally administered tissue plasminogen activator (tPA) 4 mg followed by dornase alfa 5 mg. Participants in the placebo group will receive tPA 4 mg followed by normal saline. Study treatments will be administered once daily for 3 days. All participants, parents or caregivers, clinicians, and research personnel will remain blinded. The primary outcome is length of stay from chest tube insertion to discharge from hospital. Secondary outcomes include time to meeting discharge criteria, chest tube duration, fever duration, need for additional procedures, adverse events, hospital readmission, cost of hospitalization, and mortality.

Discussion: This multicenter randomized controlled trial will assess the safety, effectiveness, and cost-effectiveness of combined treatment with dornase alfa and fibrinolytics compared to fibrinolytics alone for the treatment of empyema in children.

Trial registration: ClinicalTrials.gov: NCT01717742 . Registered on 8 October 2012.

Keywords: Chest tubes; Children; Empyema; Fibrinolytic agents; Randomized controlled trial.

Figures

Fig. 1
Fig. 1
Overview of the intrapleural Dornase and Tissue Plasminogen Activator in pediatric empyema (DTPA) trial
Fig. 2
Fig. 2
Overview of enrollment, interventions, and assessments as per the Standard Protocol Items Recommendations for Interventional Trials (SPIRIT) Statement [45]

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