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

Bacterial Pleural Effusion Other Than Tuberculosis Clinical Trial

— CPE  

Official title:

Response to Instillation of Activase in the Pleural Cavity vs Placebo in the Management of Complicated Pleural Effusion/Empyema

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468104
• Other study ID #: 11415
• Status: Completed
• Phase: N/A
• First received: April 29, 2007
• Last updated: April 25, 2012
• Start date: April 2004
• Est. completion date: August 2009

Study information

• Verified date: April 2012
• Source: Midwest Pulmonary and Critical Care
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Pleural Effusion Other Than Tuberculosis
• Empyema
• Pleural Effusion
• Pleural Effusion Associated With Pulmonary Infection
• Tuberculosis

Intervention

Drug:
• Alteplase
25 Mg of Alteplase in 100 cc of normal saline was instilled intrapeurally for daily for three days
• Placebo
Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days

Locations

Country	Name	City	State
United States	Nebraska Methodist Hospital	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
Midwest Pulmonary and Critical Care	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	No Surgical Intervention	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.	patients were followed six weeks per protocol. Most patients treated with Alteplase were also followed for up to six months	Yes
Secondary	Number of Participants With Pneumonia That Responded to Therapy	patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pneumonia	6 weeks	Yes
Secondary	Number of Participants With Pleural Effusion/Empyema That Responded to Therapy	patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pleural effusion/empyema	6 weeks	Yes
Secondary	Number of Participants With Shortness of Breath That Responded to Therapy	patients were followed for 6 weeks and clinical symptoms of resolution of shortness of breath were documented	6 weeks	Yes
Secondary	Number of Participants With Clinical Symptoms of Sepsis That Responded to Therapy	patients were followed for 6 weeks and resolution of sepsis was documented	6 weeks	Yes