## Protocol Section
### Identification Module
**NCT ID:** NCT06434324

**Brief Title:** Pleural Space Saline Irrigation in Addition to Standard Intrapleural Thrombolytic Therapy in Empyema/Complicated Parapneumonic Effusion

**Official Title:** A Study to Evaluate the Efficacy of Pleural Space Saline Irrigation in Addition to Standard Intrapleural Thrombolytic Therapy in the Management of Empyema/Complicated Parapneumonic Effusion

#### Organization Study ID Info
**ID:** 23-013234
#### Organization
**Class:** OTHER
**Full Name:** Mayo Clinic
#### Secondary ID Infos
**Domain:** US Dept of Defense
**ID:** HT9425-24-C-0010
**Type:** OTHER_GRANT
### Status Module
#### Completion Date
**Date:** 2026-05-04

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-01-04

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Mayo Clinic

#### Responsible Party

**Investigator Affiliation:** Mayo Clinic

**Investigator Full Name:** Dagny K. Anderson

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to see if there is any benefit in adding saline irrigation through a chest tube to the standard course of treatment for people diagnosed or suspected of having a pleural space infection.

**Detailed Description:** Pleural space infections portend considerable morbidity and require procedural and sometimes surgical intervention in the context of prolonged hospital stays (median length of stay has been reported as 14-19 days) for definitive management. Key aspects of management include pleural space evacuation and appropriate antimicrobial therapy. The antimicrobial regimen is initiated intravenously and is often transitioned to an oral regimen as guided by clinical improvement, radiographic improvement, and microbiologic studies though conventional bacterial cultures remain negative in as many as 40% of cases of pleural space infection. There is variability in antimicrobial duration though this is typically continued for at least 3 weeks. The MIST 2 trial investigated the role of intrapleural tissue plasminogen activator (t-PA) and dornase (DNase) in the management of pleural space infections, noting that disrupting septations and reducing pleural fluid viscosity were necessary steps to achieve successful drainage in in-vitro studies. MIST 2 demonstrated that a combination of intrapleural t-PA and DNase improved pleural space evacuation on serial chest x-ray and reduced the frequency of surgical referral and hospital length of stay.

Saline irrigation of the pleural space has been proposed to reduce stasis and dilute bacteria, cytokines, and coagulation factors, which induce pleural space organization. The Pleural Irrigation Trial was a pilot study evaluating the role of 250 cc 0.9% sodium chloride irrigation three times daily for 3 days in comparison to standard care, which included maintaining thoracostomy tubes on suction and flushing with 30 cc three times daily. Saline irrigation led to a 32.3% reduction in pleural fluid volume as assessed by computed tomography in comparison to 15.3% in the standard care arm. Fewer patients in the irrigation group were referred for surgery (OR 7.1).

To our knowledge, the efficacy of intrapleural saline irrigation in addition to fibrinolytic therapy has not been studied in comparison to fibrinolytic therapy alone. The Mayo Clinic Interventional Pulmonary practice in Rochester, MN intends to study this in the context of the inpatient pleural service, the team that is routinely consulted for patients with proven or suspected pleural space infections. This team routinely places and manages ultrasound-guided locking-loop thoracostomy tubes and additionally manages patients with thoracostomy tubes placed by intensivists, surgeons, and interventional radiologists when consulted. Our team intends to recruit hospitalized patients that meet the inclusion/exclusion criteria of the study. Those that provide informed consent to participate in the study will be randomized to usual care versus intrapleural saline irrigation + usual care.

### Conditions Module

**Conditions:**

- Pleural Infection

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Subjects will receive twice daily fibrinolytic therapy in addition to daily saline irrigation through their chest tube until the treating physician determines that the pleural space has been adequately evacuated

**Intervention Names:**

- Procedure: Saline Irrigation

**Label:** Saline Irrigation Group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Subjects will receive twice daily fibrinolytic therapy through their chest tube until the treating physician determines that the pleural space has been adequately evacuated

**Label:** Standard of Care Group

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Saline Irrigation Group

**Description:** 250 cc waves of warmed saline irrigation (up to 2000 cc) through thoracostomy tube on a daily basis

**Name:** Saline Irrigation

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Number of intrapleural fibrinolytic doses to achieve adequate pleural space evacuation (defined as \<=2.5 cm separation between parietal and visceral pleural layers on bedside ultrasound or no more than small residual effusion on clinically-directed CT chest imaging).

**Measure:** Adequate pleural space evacuation

**Time Frame:** Approximately 3 days

#### Secondary Outcomes

**Description:** Number of additional interventions to achieve satisfactory pleural space evacuation, such as additional paired lytics beyond 6 doses, ipsilateral thoracentesis, additional ipsilateral thoracostomy tube placement, surgical intervention, or discharge with an empyema tube in situ.

**Measure:** Need for additional interventions

**Time Frame:** Approximately 10 days

**Description:** Number of thoracostomy tube days from the time that treatment is initiated

**Measure:** Thoracostomy tube days

**Time Frame:** Approximately 10 days

**Description:** Number of hospital days from the time that treatment is initiated

**Measure:** Number of hospital days

**Time Frame:** Approximately 14 days

**Description:** Measured using a visual analog scale (VAS) questionnaire that assesses pain experienced during treatment utilizing a scale of 0 to 10, with 10 meaning the worst pain imaginable.

**Measure:** Pain tolerance of pleural space irrigation

**Time Frame:** Approximately 3 days

**Description:** Total number of adverse events including new/worsened respiratory failure, septic shock, hemothorax

**Measure:** Number of adverse events

**Time Frame:** Approximately 10 days

### Eligibility Module

**Eligibility Criteria:** Inclusion criteria:

* Purulent pleural fluid versus pleural fluid analysis demonstrating pH \<7.2, glucose \<60 mg/dL, positive Gram stain, or positive pleural fluid culture versus multiseptated pleural effusion with infection at top of differential diagnosis
* Patients initiating intrapleural lytic therapy under the care of the Interventional Pulmonary consult service at Mayo Clinic in Rochester, MN

Exclusion Criteria:

* Unwillingness to give informed consent
* Patients with known bleeding diathesis
* Platelet count \<50,000 per μL
* INR \>2.2 (of note, INR can be allowed to drift down or be reversed pharmacologically prior to initiation of intrapleural lytics/saline)
* Current use of systemic anticoagulation or antiplatelet therapy without the ability to hold therapy for the recommended amount of time prior to an invasive procedure (aspirin monotherapy is acceptable)
* Pregnant or nursing females, or females of child-bearing potential who decline a pregnancy test prior to enrollment
* Incarcerated patients
* Presence of ipsilateral bronchopleural fistula
* Current or recent (within past 30 days) presence of tunneled pleural catheter on the same side as the current proven/suspected pleural space infection

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Rochester

**Country:** United States

**Facility:** Mayo Clinic in Rochester

**State:** Minnesota

**Zip:** 55905

#### Overall Officials

**Official 1:**

**Affiliation:** Mayo Clinic

**Name:** Dagny Anderson, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Bedawi EO, Ricciardi S, Hassan M, Gooseman MR, Asciak R, Castro-Anon O, Armbruster K, Bonifazi M, Poole S, Harris EK, Elia S, Krenke R, Mariani A, Maskell NA, Polverino E, Porcel JM, Yarmus L, Belcher EP, Opitz I, Rahman NM. ERS/ESTS statement on the management of pleural infection in adults. Eur Respir J. 2023 Feb 2;61(2):2201062. doi: 10.1183/13993003.01062-2022. Print 2023 Feb.

**PMID:** 36229045

**Citation:** Birkenkamp K, O'Horo JC, Kashyap R, Kloesel B, Lahr BD, Daniels CE, Nichols FC 3rd, Baddour LM. Empyema management: A cohort study evaluating antimicrobial therapy. J Infect. 2016 May;72(5):537-43. doi: 10.1016/j.jinf.2016.02.009. Epub 2016 Mar 15.

**PMID:** 26987740

**Citation:** 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.

**PMID:** 21830966

**Citation:** Mismetti V, Froudarakis ME. Medical management of pleural infection: Why not saline intrapleural lavage? Clin Respir J. 2022 Nov;16(11):693-695. doi: 10.1111/crj.13548. Epub 2022 Sep 29. No abstract available.

**PMID:** 36173249

**Citation:** 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.

**PMID:** 26022948

#### See Also Links

**Label:** Mayo Clinic Clinical Trials

**URL:** https://www.mayo.edu/research/clinical-trials

## Document Section

### Large Document Module

#### Large Docs

- Date: 2024-04-24

- Filename: ICF_000.pdf

- Has ICF: True

- Has Protocol: False

- Has SAP: False

- Label: Informed Consent Form

- Size: 366679

- Type Abbrev: ICF

- Upload Date: 2024-05-22T18:41

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000013492

- Term: Suppuration

- ID: D000007239

- Term: Infections

- ID: D000007249

- Term: Inflammation

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M7819

- Name: Empyema

- Relevance: HIGH

- As Found: Empyema

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16273

- Name: Suppuration

- Relevance: LOW

- As Found: Unknown

- ID: M10293

- Name: Inflammation

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000004653

- Term: Empyema

### Intervention Browse Module - Browse Branches

- Abbrev: FiAg

- Name: Fibrinolytic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M8473

- Name: Fibrinolytic Agents

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
