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

Purpose

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	Intervention
Pleural Effusion Associated With Pulmonary Infection Bacterial Pleural Effusion Other Than Tuberculosis	Drug: Alteplase Drug: Placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Alteplase

U.S. FDA Resources

Further study details as provided by Midwest Pulmonary and Critical Care:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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:

Number of Participants With Pneumonia That Responded to Therapy [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
patients were followed for 6 weeks and resolution of sepsis was documented

Enrollment:	100
Study Start Date:	April 2004
Study Completion Date:	August 2009
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468104

Locations

United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114

Sponsors and Collaborators

Midwest Pulmonary and Critical Care

Genentech

Investigators

Principal Investigator:

George Thommi, MD

Midwest Pulmonary and Critical Care, PC

More Information

No publications provided

Responsible Party:	GEORGE THOMMI, MD, Midwest Pulmonary and Critical Care
ClinicalTrials.gov Identifier:	NCT00468104 History of Changes
Other Study ID Numbers:	11415
Study First Received:	April 29, 2007
Results First Received:	December 18, 2011
Last Updated:	April 25, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Midwest Pulmonary and Critical Care:

parapneumonic pleural effusion
empyema
TPA (Activase, Alteplase)

Additional relevant MeSH terms:

Empyema
Pleural Effusion
Tuberculosis
Suppuration
Infection
Inflammation
Pathologic Processes
Pleural Diseases
Respiratory Tract Diseases
Mycobacterium Infections
Actinomycetales Infections

Gram-Positive Bacterial Infections
Bacterial Infections
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on May 23, 2013