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

• ClinicalTrials.gov Identifier: NCT00468104
• Recruitment Status: Completed
• First Posted: May 2, 2007
• Results First Posted: April 24, 2012
• Last Update Posted: April 30, 2012
• Sponsor: Midwest Pulmonary and Critical Care
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): GEORGE THOMMI, Midwest Pulmonary and Critical Care

Study Description

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

Condition or disease	Intervention/treatment	Phase
Pleural Effusion Associated With Pulmonary Infection; Bacterial Pleural Effusion Other Than Tuberculosis	Drug: Alteplase; Drug: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Response to Instillation of Activase in the Pleural Cavity vs Placebo in the Management of Complicated Pleural Effusion/Empyema
• Study Start Date: April 2004
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: August 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Alteplase, Placebo- intapleural instillation; 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.	Drug: Alteplase; 25 Mg of Alteplase in 100 cc of normal saline was instilled intrapeurally for daily for three days; Drug: Placebo; Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days; Other Name: TPA, Activase
Active Comparator: Placebo, Alteplase -2nd arm; 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	Drug: Alteplase; 25 Mg of Alteplase in 100 cc of normal saline was instilled intrapeurally for daily for three days; Drug: Placebo; Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days; Other Name: TPA, Activase

Outcome Measures

Primary Outcome Measures :

1. No Surgical Intervention [ Time Frame: 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 :

1. Number of Participants With Pneumonia That Responded to Therapy [ Time Frame: 6 weeks ]
   patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pneumonia
2. Number of Participants With Pleural Effusion/Empyema That Responded to Therapy [ Time Frame: 6 weeks ]
   patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pleural effusion/empyema
3. Number of Participants With Shortness of Breath That Responded to Therapy [ Time Frame: 6 weeks ]
   patients were followed for 6 weeks and clinical symptoms of resolution of shortness of breath were documented
4. Number of Participants With Clinical Symptoms of Sepsis That Responded to Therapy [ Time Frame: 6 weeks ]
   patients were followed for 6 weeks and resolution of sepsis was documented

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Nebraska

Nebraska Methodist Hospital

Omaha, Nebraska, United States, 68114

Sponsors and Collaborators

Midwest Pulmonary and Critical Care

Genentech, Inc.

Investigators

• Principal Investigator: George Thommi, MD; Midwest Pulmonary and Critical Care, PC

More Information

• Responsible Party: GEORGE THOMMI, MD, Midwest Pulmonary and Critical Care
• ClinicalTrials.gov Identifier: NCT00468104
• Other Study ID Numbers: 11415
• First Posted: May 2, 2007
• Results First Posted: April 24, 2012
• Last Update Posted: April 30, 2012
• Last Verified: April 2012

Keywords provided by GEORGE THOMMI, Midwest Pulmonary and Critical Care:

parapneumonic pleural effusion; empyema; TPA (Activase, Alteplase)

Additional relevant MeSH terms:

Tuberculosis; Empyema; Pleural Effusion; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pleural Diseases; Respiratory Tract Diseases; Suppuration; Inflammation; Pathologic Processes; Tissue Plasminogen Activator; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action