Efficacy and Safety of Activase (Ateplase) vs Placebo in Complicated Pleural Effusions (CPE)/Empyemas

Midwest Pulmonary and Critical Care

Status: Completed

Conditions: Pleural Effusion Associated With Pulmonary Infection; Bacterial Pleural Effusion Other Than Tuberculosis

Treatments: Drug: Alteplase; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00468104

11415

Details and patient eligibility

About

The purpose of this study is to document the efficacy and safety of intrapleural instillation of Activase vs Placebo in the management of complicated pleural effusions and empyemas

Full description

The current treatments available for complicated pleural effusions (CPE) include chest tube placement for drainage and IV antibiotics. If this fails and CPE occurs then in most patients thoracotomy is performed. Patients that are not surgical candidates have image guided catheter placement performed, sometimes multiple times. The American College of Chest Physicians (ACCP) formed a CPE panel and published guidelines for treating CPE. Percutaneous image-guided drainage is the most common approach for CPE. The panel recognizes the cumulative data that supports the use of fibrinolytics, VATS, and thoracotomy. The CPE panel acknowledged the lack of randomized clinical trials to determine efficacy and safety of these modalities in CPE and strongly encourages the research to take place.

Fibrinolytic therapy is a relatively noninvasive, easy to use, and is relatively inexpensive. If successful, it will prevent sepsis and septic shock, decrease hospital stay, morbidity and mortality and prevent any surgical procedures. Multiple doses of fibrinolytics have been used in CPE with no evidence of systemic anti-fibrinolytic activity. Complications with these medications are also very uncommon and only isolated instances are reported. The benefit from successful pleural drainage using these agents will decrease morbidity, mortality, surgical procedures, and hospital stay.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Diagnosed with complicated pleural effusions
• Ability to provide written informed consent and comply with study assessments for the full duration of the study.
• Age > 18 years

Exclusion Criteria

• Current use of oral anticoagulants (e.g., warfarin sodium) with an International Normalized Ratio (INR) >5- Activated partial thromboplastin time (aPPT) > 80, Platelet count < 100,000/mm3;
• Severe uncontrolled hypertension
• Recognized hypersensitivity to Activase; or any component of its formulation; Traumatic pleural effusion
• Pregnancy (positive pregnancy test)
• In another study for this condition
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
• Participation in another simultaneous medical investigation
• Recent stroke
• Intracranial hemorrhage
• arteriovenous malformation or aneurysm
• Intracranial neoplasm
• Acute myocardial infarction
• Acute pulmonary embolus

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups

Alteplase, Placebo- intapleural instillation

Active Comparator group

Description:

Either 25 mg of Alteplase or Placebo instilled daily. Response to therapy after three days. cross over to the other drug if no response was noted.

Treatment:

Drug: Placebo

Drug: Alteplase

Placebo, Alteplase -2nd arm

Active Comparator group

Description:

If the first arm fails then the 2nd arm ( cross over to either Placebo or Alteplase not used in the first arm) instilled intrapleurally daily for three days

Treatment:

Drug: Placebo

Drug: Alteplase