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

Primary Purpose

Pleural Effusion Associated With Pulmonary Infection, Bacterial Pleural Effusion Other Than Tuberculosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Alteplase
Placebo
Sponsored by
Midwest Pulmonary and Critical Care
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pleural Effusion Associated With Pulmonary Infection focused on measuring parapneumonic pleural effusion, empyema, TPA (Activase, Alteplase)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Nebraska Methodist Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Alteplase, Placebo- intapleural instillation

Placebo, Alteplase -2nd arm

Arm 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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
Number of Participants With Clinical Symptoms of Sepsis That Responded to Therapy
patients were followed for 6 weeks and resolution of sepsis was documented

Full Information

First Posted
April 29, 2007
Last Updated
April 25, 2012
Sponsor
Midwest Pulmonary and Critical Care
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00468104
Brief Title
Efficacy and Safety of Activase (Ateplase) vs Placebo in Complicated Pleural Effusions (CPE)/Empyemas
Acronym
CPE
Official Title
Response to Instillation of Activase in the Pleural Cavity vs Placebo in the Management of Complicated Pleural Effusion/Empyema
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Midwest Pulmonary and Critical Care
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pleural Effusion Associated With Pulmonary Infection, Bacterial Pleural Effusion Other Than Tuberculosis
Keywords
parapneumonic pleural effusion, empyema, TPA (Activase, Alteplase)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alteplase, Placebo- intapleural instillation
Arm Type
Active Comparator
Arm 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.
Arm Title
Placebo, Alteplase -2nd arm
Arm Type
Active Comparator
Arm 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
Intervention Type
Drug
Intervention Name(s)
Alteplase
Intervention Description
25 Mg of Alteplase in 100 cc of normal saline was instilled intrapeurally for daily for three days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
TPA, Activase
Intervention Description
Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days
Primary Outcome Measure Information:
Title
No Surgical Intervention
Description
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.
Time Frame
patients were followed six weeks per protocol. Most patients treated with Alteplase were also followed for up to six months
Secondary Outcome Measure Information:
Title
Number of Participants With Pneumonia That Responded to Therapy
Description
patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pneumonia
Time Frame
6 weeks
Title
Number of Participants With Pleural Effusion/Empyema That Responded to Therapy
Description
patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pleural effusion/empyema
Time Frame
6 weeks
Title
Number of Participants With Shortness of Breath That Responded to Therapy
Description
patients were followed for 6 weeks and clinical symptoms of resolution of shortness of breath were documented
Time Frame
6 weeks
Title
Number of Participants With Clinical Symptoms of Sepsis That Responded to Therapy
Description
patients were followed for 6 weeks and resolution of sepsis was documented
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Thommi, MD
Organizational Affiliation
Midwest Pulmonary and Critical Care, PC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States

12. IPD Sharing Statement

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

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