Efficacy of Post-operative Antibiotic Prophylaxis for Thoracic Surgery Requiring Tube Thoracostomy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if post-operative antibiotic prophylaxis decreases infectious complications when compared to pre-operative antibiotics alone, in patients undergoing elective thoracic surgery requiring tube thoracostomy (chest tube).

Detailed Description
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There is currently no evidence-based standard for the extended use of prophylactic antibiotics in patients receiving thoracic surgery that results in the placement of a tube thoracostomy (chest tube). The rationale for this prophylaxis is that antibiotics directed at typical skin flora may reduce the rate of infectious complications, such as surgical site infection and empyema. Currently, clinicians' approach to post-operative antibiotic prophylaxis in patients undergoing tube thoracostomy associated with thoracic and cardio-thoracic surgery varies widely. While reducing the infectious complications of thoracic surgery is an important goal, it is also important to reduce the use of unnecessary antibiotics. As there is equipoise on the benefit of extended antibiotic prophylaxis for tube thoracostomy, our study will examine two prevailing clinical practices and attempt to determine if one leads to better patient outcomes.

Official Title
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Extended Antibiotic Prophylaxis for the Prevention of Infectious Complications Associated With Tube Thoracostomy in Patients Undergoing Elective General Thoracic Surgery: A Double-Blind, Placebo-Controlled, Randomized Trial

Conditions
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Antibiotic Prophylaxis

Intervention / Treatment
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* Drug: cefazolin or vancomycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 years or older undergoing elective thoracic surgery at Brigham & Women's Hospital. The majority of these patients will be undergoing lung resection for either the evaluation of a lung mass, or for the removal of a known malignancy. Some participants may be undergoing biopsy or removal of a mediastinal mass. Undergoing thoracic surgery procedure expected to require tube thoracostomy. Ability to give informed consent Exclusion Criteria: Patients undergoing the following complex thoracic surgical procedures: Pneumonectomy Decortication Chemical pleurodesis Pleurectomy Lung volume reduction Esophagectomy Patients with the following conditions: Prior diagnosis of empyema or lung abscess. Cystic fibrosis Known or suspected pneumonia pre-operatively. Known hypersensitivity to beta-lactam antibiotics and vancomycin Current or recent antibiotic use within one week of surgery. Anticipated requirement for postoperative antibiotic in addition to 48 hours of cefazolin or vancomycin. Renal insufficiency with estimated creatinine clearance <60 ml/minute.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antibiotic<br>Participants received intravenous (IV) cefazolin or vancomycin (for participants allergic to cephalosporin) immediately following surgery for 48 hours or until all chest tubes were removed, whichever occurred first. | Drug: cefazolin or vancomycin<br>* Cefazolin IV every eight hours post-operatively for 48 hours or until all chest tubes were removed, whichever occurred first. Participants under 80 kg received 1 gram of cefazolin and participants who were 80 kg or more received 2 grams of cefazolin. Participants who were penicillin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.<br>* Other names: Vancomycin (Vancocin);|
| Placebo Comparator: Placebo<br>Participants received IV placebo-matching antibiotics immediately following surgery for 48 hours or until all chest tubes were removed, whichever occurred first. | Drug: Placebo<br>* Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced At Least One Postoperative Infectious Complication | Infectious complications include: surgical site infection, empyema, pneumonia, and the occurrence of Clostridium difficile colitis within 28 days of surgery. Participants are only counted once regardless of how many different infectious complications they had. | Up to 28 days after surgery | 
| Number of Participants Who Experienced Surgical Site Infection | Surgical Site Infection: Superficial surgical site infection - involves only skin or subcutaneous tissue around incision and has at least one of the following criteria: purulent drainage organisms isolated from aseptically obtained culture pain or tenderness, localized swelling, redness or heat and the incision deliberately opened by a surgeon diagnosis of a superficial wound infection by a surgeon Deep surgical site infection - involves deep soft tissues e.g. fascia or muscle and has at least one of the following: purulent drainage from the incision but not from the organ/space of the surgical site deep incision spontaneously dehisces or deliberately opened by surgeon when patient has at least one of following signs or symptoms - fever (>38°C), localized pain or tenderness. an abscess or evidence of infection involving incision is found on direct examination, histopathologic or radiographic examination diagnosis of a deep wound infection | Up to 28 days after surgery | 
| Number of Participants Who Experienced Pneumonia | Pneumonia: A new infiltrate on chest x-ray associated with at least three of the following: fever (>38°C) purulent sputum leukopenia (white blood cell [WBC] count of <4000/µL) or leukocytosis (WBC count of >11000/µL) sputum culture with pathogenic bacteria increased oxygen requirements | Up to 28 days after surgery | 
| Number of Participants Who Experienced Empyema | Empyema: Positive pleural culture result or purulence within the thoracic space and leukocytosis or fever (>38°C). | Up to 28 days after surgery | 
| Number of Participants Who Experienced Clostridium (C) Difficile Colitis | C. Difficile Colitis: Positive for C difficile toxin assay results and any 1 of the following: new diarrhea ileus or toxic megacolon leukopenia (WBC count of <4000/µL) or leukocytosis (WBC count of >11000/µL) findings from sigmoidoscopy, colonoscopy, or histopathologic examination consistent with C difficile infection | Up to 28 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Received Additional Antibiotics for Any Reason Within 28 Days After Surgery | The number of participants who needed any additional non-study antibiotics for any reason after randomization. | Up to 28 days after surgery | 
| Number of Participants Who Needed Reoperation | The number of participants who needed reoperations for any reason from the time after the first surgery to the end of the 28-day follow-up period. | Up to 28 days after surgery | 
| Length of Hospital Stay | The length of hospital stay is the number of days the participant remained in the hospital. | From day of surgery to discharge (up to 35 days) | 
| Time to Removal of Chest Tubes | Time to removal of chest tubes is the number of days from the time of chest tube placement to time they were removed. | From day of surgery to removal of chest tubes (up to 33 days) | 
| Number of Participants With Allergic Reactions | The number of participants with an allergic reaction to a drug. | Up to 28 days after surgery | 
| All-Cause Mortality | All-cause mortality is the number of deaths that occurred during the study period, regardless of the cause. | Up to 28 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thoracic Surgery, Antibiotic Prophylaxis, Chest Tube