Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alteplase, Placebo- intapleural instillation | Active Comparator | 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 | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alteplase | Drug | 25 Mg of Alteplase in 100 cc of normal saline was instilled intrapeurally for daily for three days |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Number of Participants With Pleural Effusion/Empyema That Responded to Therapy |
Not provided
Inclusion Criteria:
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| George Thommi, MD | Midwest Pulmonary and Critical Care, PC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nebraska Methodist Hospital | Omaha | Nebraska | 68114 | United States |
108 patients were evaluated but only 100 entered the trial. 2 patients refused, 2 patients admitting physicians opted out of the trial, 3 patients chest tube removed inadvertently, 1 patient for coagulopathy
Patients with loculated pleural effusions that failed to respond to chest tube placement and standard medical treatment and were considered for surgery were given the option to enter into a double blind cross over trial
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Alteplase Then Placebo | 25 mg of Alteplase in 100 cc of normal saline was instilled intrapleurally daily for three days. Chest CT scans were performed on the fourth day . If less than a 50% reduction in the pleural effusion was determined, the patient was given the option to go to surgery or to the second intervention of the trial (with Placebo) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days |
|
|
patients were followed for 6 weeks and CXR and CT scan were done to document resolution of pleural effusion/empyema |
| 6 weeks |
| 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 |
| 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 |
| FG001 |
| Placebo Then Alteplase |
Placebo in 100 cc of normal saline was instilled intrapleurally daily for three days. Chest CT scans were performed on the fourth day . If less than a 50% reduction in the pleural effusion was determined, the patient was given the option to go to surgery or to the second intervention of the trial (with Alteplase) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Second Intervention |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Alteplase; Placebo | 25mg of Alteplase in 100 cc of normal saline instilled intrapleurally; 100 cc of normal saline instilled intrapleurally |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | intention to treat | Posted | Number | participants | patients were followed six weeks per protocol. Most patients treated with Alteplase were also followed for up to six months |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed | Posted | Number | participants | 6 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed | Posted | Number | participants | 6 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed | Posted | Number | participants | 6 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | protocol design prevented assigning symptom resolution to a specific intervention therefore secondary outcome measures in 6 weeks were not analyzed | Posted | Number | participants | 6 weeks |
|
|
soon after drug instillation and for the first 24 hours in the hospital and then followed up for six months
adverse events that occurred in patients after they received both Alteplase and Placebo were placed in a separate group as we were unable to determine which intervention ( Alteplase or Placebo) caused the problem
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Received Alteplase Only | These patients received only Alteplase and were not crossed over | 1 | 42 | 10 | 42 | ||
| EG001 | Received Placebo Only | These patients received Placebo only and were not crossed over | 0 | 8 | 5 | 8 | ||
| EG002 | Received Both Alteplase and Placebo | These patients were crossed over and received both Alteplase and Placebo | 0 | 40 | 8 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| serious bleeding at the chest tube site | Skin and subcutaneous tissue disorders | Systematic Assessment | bleeding occurred soon after Alteplase instillation at the chest tube site--patient needed transfusion and was taken off the trial |
| |
| Shortness of breath, worsening sepsis | General disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| severe chest pain post drug instillation | General disorders | Systematic Assessment |
| ||
| mild to moderate chest pain | General disorders | Systematic Assessment |
| ||
| hypotension and worsening renal function | General disorders | hypotension | Systematic Assessment | congestive heart failure, cardiomyopathy and malignant pleural effusions patients had significant pleural fluid loss both with Alteplase and Placebo. These patients need careful fluid status and diuretics monitoring. |
|
| blood loss--pleural fluid | Blood and lymphatic system disorders | other | Systematic Assessment | Patients effusion were bloody to start with and decreasing hemoglobin was noted over 2-3 days post drug instillation needing blood transfusion |
|
| increasing shortness of breath | Respiratory, thoracic and mediastinal disorders | other | Systematic Assessment | increasing SOB secondary to increasing pleural fluid |
|
| worsening sepsis | Infections and infestations | Systematic Assessment |
|
The sample size for secondary outcomes in the Placebo group is small
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| George Thommi | Midwest Pulmonary and critical care | 402 206 7372 | tommi4@cox.et |
| ID | Term |
|---|---|
| D004653 | Empyema |
| ID | Term |
|---|---|
| D013492 | Suppuration |
| D007239 | Infections |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
Not provided
Not provided