Flush, Lyse, Operate (FLO)

Flush, Lyse, Operate: A Pilot Trial of Step-Wise Escalation for Pleural Infection: FLO Trial

The goal of this observational study is to learn if saline results in improvement for patients with infection of their plerual space. The main question it aims to answer is:

What is the time to chest tube removal? Do these patients after need to escalate to fibrinolytics? Do these patients after need to escalate to surgery?

Participants will:

• Receive receive saline into their pleural space through an existing chest tube
• If they fail to improve, which will be determined by fluid size after treatment or signs of persistent infection, they will receive fibrynolytics through an existing chest tube
• If they fail to improve, which will be determined by fluid size after treatment or signs of persistent infection, they will be referred to surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Empyema, Pleural; Complicated Parapneumonic Effusion
• Intervention / Treatment: Drug: Intrapleural Saline with possible escalation to intraplerual alteplase and dornase.

Detailed Description

Patients who require a chest tube for complicated parapneumonic effusion or empyema who meet inclusion criteria and consent, will be enrolled. An ultrasound measurement of the original effusions prior to chest tube placement will be obtained then chest tube insertion will follow as well as an additional US measurement once placed. After appropriate positioning is confirmed, there will be instillation of intrapleural saline and will be administered every 8 hours for a total of 3 days. After completion of the intrapleural saline course, the effusion will be remeasured by ultrasound. Should the effusions fail to reduce by 75% or significant septations remain, the patient will then be escalated to intrapleural tPA/DNase which will be administered every 12 hours for 3 days. After the completed course of tPA/DNase, a US will be performed, and if significant fluid remains, >50% of the original effusion or septations remain, Thoracic Surgery consultation will be placed for discussion of VATs.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Hanover, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
      • Contact: Adele E Soutar, MD; Phone Number: 603-650-5000; Email: adele.e.soutar@hitchcock.org
      • Sub-Investigator: Jimmy Wang, MD
      • Sub-Investigator: David Feller-Kopman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18+
• Complicated Parapneumonic Effusion or Empyema Requiring Thoracostomy
• Are able to personally or have a designated medical decision maker provide consent

Exclusion Criteria:

• Age < 18 years
• Have received any intrapleural medications prior to enrolment via current chest tube

• Have a contraindication to tPA/DNase:

  • Anticoagulation
  • Active hemorrhage
  • Allergy to tPA/DNase
  • Pregnancy
• Are unable to personally or do not have a designated medical decision maker provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Intraplerual Saline; All patients will be in a single arm and escalated from intraplerual saline to tPA/DNAse followed by surgery as warranted based on protocol criteria.

Drug: Intrapleural Saline with possible escalation to intraplerual alteplase and dornase.; Though intraplerual alteplase/ dornase alfa and normal saline have been established method to reduce complicated pleural infection sizes and rate of surgical interventions, with tPA/DNAse being the gold standards, there has not been a study comparing the two head to head. This trial's purpose is to function as pilot study as a foundation for a potential noninferiorrity trail comparing the two.; Other Names: normal saline; alteplase; dornase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to chest tube removal	measuring the length of time from chest tube insertion to removal	From enrollment to removal- estimated up to 7 days. Once chest tube is placed, it will take 3 days for saline course to be completed and, if escalated, 3 days for intrapleural fibrinolytics, therefore may not be removed until after 7 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for escalation to fibrinolytics	Rate of patients requiring intraplerual tPA/DNAse after completion of intrapleural saline	From enrollment to chest tube removal- up to 7 days. Once chest tube is placed, it will take 3 days for saline course to be completed and, if escalated, 3 days for intrapleural fibrinolytics, therefore may not be removed until after 7 days.
Need for escalation to Video-assisted thoracic surgery (VATS)	Evaluation fo patients who require Video-assisted thoracic surgery (VATS) after completion of intraplerual saline and tPA/DNAse	From enrollment to chest tube removal- up to 7 days. Once chest tube is placed, it will take 3 days for saline course to be completed and 3 days for intrapleural fibrinolytics, therefore VATs determined after, about 7 days.
Rate of hemothorax.	Evaluating number of patients who develop a hemothorax	From enrollment to chest tube removal- up to 7 days. Once chest tube is placed, it will take 3 days for saline course to be completed and, if escalated, 3 days for intrapleural fibrinolytics, therefore may not be removed until after 7 days.
Length of Hospital Stay	Quantifying the length of hospital stay for all patients enrolled	From enrollment to discharge- up to 52 weeks.
Mortality	Rate of 30 day all cause mortally	30 days from enrollment: rate of documented death prior or up to 30 days.

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center

Publications and helpful links

General Publications

• Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat Methods Med Res. 2016 Jun;25(3):1057-73. doi: 10.1177/0962280215588241. Epub 2015 Jun 19.
• Billingham SA, Whitehead AL, Julious SA. An audit of sample sizes for pilot and feasibility trials being undertaken in the United Kingdom registered in the United Kingdom Clinical Research Network database. BMC Med Res Methodol. 2013 Aug 20;13:104. doi: 10.1186/1471-2288-13-104.
• Hooper CE, Edey AJ, Wallis A, Clive AO, Morley A, White P, Medford AR, Harvey JE, Darby M, Zahan-Evans N, Maskell NA. Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection. Eur Respir J. 2015 Aug;46(2):456-63. doi: 10.1183/09031936.00147214. Epub 2015 May 28.
• 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.
• Maskell NA, Davies CW, Nunn AJ, Hedley EL, Gleeson FV, Miller R, Gabe R, Rees GL, Peto TE, Woodhead MA, Lane DJ, Darbyshire JH, Davies RJ; First Multicenter Intrapleural Sepsis Trial (MIST1) Group. U.K. Controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med. 2005 Mar 3;352(9):865-74. doi: 10.1056/NEJMoa042473.
• Hassan M, Rizk R, Essam H, Abouelnour A. Validation of equations for pleural effusion volume estimation by ultrasonography. J Ultrasound. 2017 Oct 27;20(4):267-271. doi: 10.1007/s40477-017-0266-1. eCollection 2017 Dec.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Inflammation; Suppuration; Pleural Diseases; Pathological Conditions, Signs and Symptoms; Empyema; Empyema, Pleural; Amino Acids, Peptides, and Proteins; Proteins; Pharmaceutical Preparations; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Saline Solution; dornase alfa
• Other Study ID Numbers: STUDY02003106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No