Clinical trial NCT06713382: Evaluating the Efficacy and Safety of Saline Irrigation as an Add-On Therapy for Retained Pleural Infections [LYTICS +]
Official title: Evaluating the Efficacy and Safety of Saline Irrigation as an Add-On Therapy for Retained Pleural Infections (LYTICS +)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pleural Effusion Associated With Pulmonary Infection
Pleural Effusion Disorder
Pleural Effusions
Keywords: Pleural Effusion
Thoracentesis
Tissue Plasminogen Activator
DNase
Therapeutic Irrigation
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
First posted: 2024-12-03
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: - Control Group (Standard Care):

Patients will receive the current standard of care, which includes antibiotics, chest tube placement, and intrapleural tPA/DNase therapy based on the criteria outlined above.

- Intervention Group (Standard Care + Saline Irrigation):

In addition to the standard care, patients in this group will receive pleural saline irrigation through the chest tube immediately after IPFT. The amount of saline will be determined by free-flow saline infusion up to 250 mL. This maneuver will be repeated every time that IPFT is administered, based on treating physician's criteria
Primary purpose: TREATMENT

Brief summary: The purpose of this protocol is to conduct a pilot prospective non-blind clinical trial to evaluate the efficacy and safety of a novel saline irrigation technique as an adjunct to standard interventions for treating retained pleural infections. Intrapleural fibrinolytic therapy (IPFT) is commonly used for infections not adequately managed with antibiotics and intercostal tube drainage, while saline irrigation serves as an alternative for cases with a high bleeding risk where IPFT is not feasible. The efficacy of saline irrigation combined with IPFT remains unexplored. The hypothesis is that saline irrigation could be an effective and safe addition to IPFT for patients with persistent pleural infections.

The specific aims of the study include:

Determine the efficacy of saline irrigation as add-on therapy to IPFT: Compare the clinical outcomes of patients receiving saline irrigation combined with IPFT to those receiving IPFT alone to determine if the addition of saline irrigation offers significant benefits. Outcomes include changes in inflammatory markers, imaging characteristics (echography and CT), volume of pleural fluid drained, chest tube duration, hospital length of stay, and the need for subsequent surgical intervention.

Assess the safety and tolerability of saline irrigation plus IPFT: Compare complications and patient comfort in those receiving saline irrigation combined with IPFT to those receiving IPFT alone.

Detailed description: Objective:

To evaluate the efficacy and safety of pleural saline irrigation as an adjunct therapy in patients with retained pleural infection, comparing it with the standard of care (antibiotics, chest tube placement, and lytics).

Study Design:

This is a prospective, two-arm pilot trial to be conducted at Beth Israel Deaconess Medical Center. The study will involve two groups: one receiving standard care and the other receiving pleural saline irrigation in addition to standard care. Patients will be assigned to one of the two study arms (standard care vs. standard care + saline irrigation) using block randomization to ensure balanced group sizes.

Interventions:

Control Group (Standard Care):

Patients will receive the current standard of care, which includes antibiotics, chest tube placement, and intrapleural tPA/DNase therapy based on the criteria outlined above.

Intervention Group (Standard Care + Saline Irrigation):

In addition to the standard care, patients in this group will receive pleural saline irrigation through the chest tube immediately after IPFT. The amount of saline will be determined by free-flow saline infusion up to 250 mL. This maneuver will be repeated each time IPFT is administered, based on the treating physician's criteria.

Outcomes:

Primary Endpoint:

The primary outcome is the reduction in pleural effusion volume, measured with CT (volumetry) and US (Balik formula), with efficacy defined as a 10% or greater improvement compared to standard care alone. Success will be determined by a ≥10% additional reduction in pleural effusion volume compared to regular interventions.

Secondary Endpoints:

Rate of pleural infection resolution based on clinical (fever), radiographic (ultrasound and CT signs of complicated pleural effusion), and laboratory (inflammatory markers) data.

Chest tube duration. Duration of hospital stay. Complications related to the interventions. Pain associated with the interventions. Need for surgery. Overall mortality.

Data Collection and Variables:

A range of variables will be collected to assess both primary and secondary outcomes. Primary outcome measures will focus on the percentage reduction in pleural effusion volume, assessed through chest ultrasound or CT scan at baseline and during follow-up. Secondary outcomes include adverse events related to the intervention, such as hypothermia, chest discomfort, and fluid overload. The incidence of pleural infection-related complications, recurrence of infection, and the need for further pleural interventions, such as thoracentesis or chest tube placement, will be monitored. Chest tube duration, fever duration, leukocytosis, neutrophil count, and blood culture results will be evaluated to track infection resolution and patient recovery.

Subgroup analysis will be performed based on pleural fluid volume and characteristics (pH, glucose, LDH), antibiotic duration, and follow-up imaging results, both at the end of therapy and 3-6 weeks later. Other intervention-related variables, such as the amount and frequency of saline irrigation, chest tube size, intrapleural tPA/DNase doses, and the total volume of fluid drained, will also be collected to further assess the intervention's efficacy and safety.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years.
* Presence of purulent pleural fluid or pleural fluid analysis with any of the following:
* pH ≤ 7.2.
* Glucose \< 40 mg/dL.
* LDH \> 1000 IU/L.
* Presence of bacterial or fungal organisms on Gram stain or culture.
* Chest tube placement with less than 200 mL drainage in 24 hours.
* Indication for IPFT treatment based on treating physician's criteria.
* Radiographic evidence of septations on chest ultrasound (US) or loculations on low-dose chest computed tomography (CT).

Exclusion Criteria:

* Inability to provide informed consent.
* Pregnant patients.
* Patients with significant comorbidities that may interfere with the study -outcomes (e.g., terminal malignancy).
* Complicated sympathetic effusion.
* Hepatic hydrothorax.

Primary outcomes:
measure: Reduction in Pleural Effusion Volume
timeFrame: Baseline (prior to intervention). During hospitalization (before each IPFT and irrigation session, anticipated every 24 hours, up to 14 days). At discharge (7-14 days post-intervention initiation). Follow-up at 3 weeks (+/- 3 days) and 6 weeks (+/- 3 day
Secondary outcomes:
measure: Rate of pleural infection resolution
timeFrame: Baseline, at discharge (7-14 days post-intervention initiation), and follow-up (3 weeks +/- 3 days and 6 weeks +/- 3 days post-discharge).
measure: Chest tube duration
timeFrame: Through hospitalization (up to 14 days).
measure: Length of hospital stay
timeFrame: Through hospitalization (anticipated 7-14 days).
measure: Complications related to the interventions
timeFrame: During hospitalization (up to 14 days) and at follow-up (3 weeks +/- 3 days and 6 weeks +/- 3 days post-discharge).
measure: Pain associated with interventions
timeFrame: During hospitalization (measured immediately after each intervention session, anticipated up to 14 days).
measure: Need for surgical intervention
timeFrame: Through study completion (up to 6 weeks post-discharge).
measure: Overall mortality
timeFrame: Through study completion (up to 6 weeks post-discharge).
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Adnan Majid, MD
role: PRINCIPAL_INVESTIGATOR
References: