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

Not Applicable

Completed

• Conditions: Pleural Effusion Associated With Pulmonary Infection; Bacterial Pleural Effusion Other Than Tuberculosis
• Interventions: Drug: Alteplase; Drug: Placebo

• Registration Number: NCT00468104
• Lead Sponsor: Midwest Pulmonary and Critical Care

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 2004-04
• Study First Submitted: 2007-04-29
• Study First Submitted QC: 2007-05-01
• Study First Posted: 2007-05-02
• Primary Completion: 2008-10
• Study Completion: 2009-08
• Results First Submitted: 2011-12-18
• Status Verified: 2012-04
• Results First Submitted QC: 2012-04-07
• Results First Posted: 2012-04-24
• Last Update Submitted: 2012-04-25
• Last Update Posted: 2012-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Alteplase, Placebo- intapleural instillation	Alteplase	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.
Alteplase, Placebo- intapleural instillation	Placebo	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.
Placebo, Alteplase -2nd arm	Placebo	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
Placebo, Alteplase -2nd arm	Alteplase	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

Primary Outcome Measures

Name	Time	Method
No Surgical Intervention	patients were followed six weeks per protocol. Most patients treated with Alteplase were also followed for up to six months	CT scans of the chest and Chest X rays (CXR) were used to determine resolution of Pleural effusions/empyema/ pneumonia after 3 days of Alteplase/ Placebo therapy. If no response was noted with the first intervention patients were offered surgery --Decortiation/ Video Assisted Thoracic Surgery (VATS) or to receive the second intervention. Patients that failed the second intervention were offered surgery.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Pneumonia That Responded to Therapy	6 weeks	patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pneumonia
Number of Participants With Pleural Effusion/Empyema That Responded to Therapy	6 weeks	patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pleural effusion/empyema
Number of Participants With Shortness of Breath That Responded to Therapy	6 weeks	patients were followed for 6 weeks and clinical symptoms of resolution of shortness of breath were documented
Number of Participants With Clinical Symptoms of Sepsis That Responded to Therapy	6 weeks	patients were followed for 6 weeks and resolution of sepsis was documented

Trial Locations

Locations (1)

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States