Thoracentesis to Alleviate Cardiac Pleural Effusion

Study Overview
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Brief Summary
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The present study will examine the comparative effectiveness of two treatment strategies currently used in the treatment of patients with systolic heart failure presenting with pleural effusion. Patients will be randomized to standard medical treatment only or medical treatment and referral to thoracentesis. Study hypothesis: A strategy of referring patients with heart failure-related pleural effusion to thoracentesis increases number of days alive outside of hospital over the following 90 days.

Detailed Description
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Purpose and Rationale: Pleural effusion is a common presentation in patients with heart failure, and the condition is related to a poor prognosis and increased mortality. Therapeutic options consist of intensification of diuretic treatment and invasive drainage of the effusion (thoracentesis). Thoracentesis is a common medical procedure and is often performed on patients with heart failure presenting with a pleural effusion, but there is no randomized evidence to guide the use of thoracentesis in heart failure-related pleural effusion. International guidelines provide no recommendations. Some Danish hospitals use thoracentesis frequently, some rarely. Hence, there is true clinical equipoise and a strong need to assess whether thoracentesis benefits patients or not. Study Hypothesis: A strategy of referring patients with heart failure-related pleural effusion to thoracentesis increases number of days alive outside of hospital over the following 90 days. Study Setting:126 adult patients admitted with systolic heart failure and pleural effusion documented by either chest x- ray, ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) will be randomized 1:1 to medical treatment only or medical treatment and referral to thoracentesis. Thoracentesis will be performed according to local practice. Randomization will be stratified according to whether patients are treated with oral anticoagulation. Crossover/rescue thoracentesis: For patients in the medical treatment arm whose condition deteriorates to the degree that the participant fulfill any of the study exclusion criteria (eg. increased need of oxygen), thoracentesis may be performed immediately. Some patients randomized to medical treatment only may prove to be too diuretic resistant to achieve an adequate effect of medical treatment alone. The recommended waiting period before performing thoracentesis on a patient in the control group is 5 days from randomization. Patients may be discharged at the discretion of the treating physician. The follow up period is planned to 90 days.

Official Title
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Thoracentesis to Alleviate Cardiac Pleural Effusion - an Interventional Trial (TAP-IT)

Conditions
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Heart Failure, Pleural Effusion

Intervention / Treatment
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* Procedure: Thoracentesis
* Drug: Standard-of-care medical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Left ventricular ejection fraction (LVEF) ≤ 45% Non- negligible pleural effusion by x-ray, ultrasound, CT or MRI, suspected to be due to heart failure Age ≥ 18 years Exclusion Criteria: Clinically indicated diagnostic thoracentesis (e.g. suspected malignant aetiology) Suspected pulmonary or pleural infection (pneumonia symptoms with c- reactive protein>100 mg/L or white blood count>11) Recent (<3 months) intrathoracic procedure (including heart or lung surgery, transcatheter aortic valve implantation (TAVI) or thoracentesis) Contraindications to thoracentesis according to local guidelines (such as spontaneously elevated international normalized ratio (INR) or thrombocytopenia), patients on oral anticoagulation may be randomized. Severe aortic stenosis Massive pleural effusion (equivalent to >2/3 of lung on a standing chest x-ray) Substantially affected hemodynamics (systolic blood pressure < 85mmHg, need of inotropes) or high oxygen demand (>7L/min) Estimated glomerular filtration rate (eGFR) <15ml/min/1.73m2 or dialysis treatment Planned or expected admission > 10 days for other condition than heart failure Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial is a pragmatic controlled, randomized, multicenter open label trial with including patients admitted with pleural effusion related to systolic heart failure. Patients will be randomized 1:1 to standard-of-care medical treatment only or standard-of-care medical treatment and referral to thoracentesis. Randomization will be stratified according to whether patients are treated with oral anticoagulation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Standard-of-care medical treatment. | Drug: Standard-of-care medical treatment<br>* Standard-of-care medical treatment<br>|
| Experimental: Intervention group<br>Thoracentesis in addition to standard-of-care medical treatment. | Procedure: Thoracentesis<br>* Thoracentesis will be performed according to local practice, either at the ward or at the radiology department, in addition to standard-of-care medical treatment.<br>* Other names: Pleurocentesis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive outside of hospital (days) | Number of days the patient is alive outside of hospital in the 90 days following randomization | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satisfaction with hospital stay (Likert scale) | Selected questions from the questionnaire Questions about your admission from the annual Danish National Survey of Patient Experiences to assess satisfaction with index admission. Likert scale from 1-5. 5 represents the best outcome. | Up til 1 week after discharge | 
| Kansas City Cardiomyopathy Questionnaire (KCCQ-23) (score) | Kansas City Cardiomyopathy Questionnaire (KCCQ). Selected scores from the 23-item questionnaire at 14 and 90 days. Scores from 0-100 with 100 representing the best outcome. | At 14 days and 90 days - up til 1 week | 
| Complications during hospital stay (count) | Number of complications during the index admission (eg. infections, delirium, falls, thrombosis) | From randomization until the date af discharge from hospital. Estimated time frame from 2 days to 3 weeks. | 
| Complications to thoracentesis (count) | Number of complications to interventional thoracentesis | From randomization until the date af discharge from hospital. Estimated time frame from 2 days to 3 weeks. | 
| Duration of index admission (days) | Duration of index admission following randomization. | From randomization until the date af discharge from hospital. Estimated time frame from 2 days to 3 weeks. | 
| Changes from baseline in weight during admission (kg) | Changes in weight during admission | From randomization until the date af discharge from hospital. Estimated time frame from 2 days to 3 weeks. | 
| Change from baseline in dosage of diuretics during admission (mg/day) | Change in dosage of diuretics during index admission | From randomization until the date af discharge from hospital. Estimated time frame from 2 days to 3 weeks. | 
| Time to death (days) |  | 90 days | 
| Time to first readmission or death (days) |  | 90 days | 
| Days alive and not hospitalized due to heart failure during the 90 days following randomization. |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Systolic heart failure, Pleural effusion, Thoracentesis, Thoracocentesis, Pleurocentesis