Trial Outcomes & Findings for Efficacy of Post-operative Antibiotic Prophylaxis for Thoracic Surgery Requiring Tube Thoracostomy (NCT NCT00818766)

NCT ID: NCT00818766

Last Updated: 2017-04-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 251 participants
• Primary outcome timeframe: Up to 28 days after surgery
• Results posted on: 2017-04-26

Participant Flow

Patients presenting for elective lung surgery and expected to require tube thoracostomy were approached for participation in the study at the time of preoperative evaluation.

Participant milestones

Measure	Antibiotic Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Overall Study STARTED	125	126
Overall Study Received Allocated Intervention	122	126
Overall Study Intent-to-Treat Population	121	124
Overall Study COMPLETED	110	116
Overall Study NOT COMPLETED	15	10

Reasons for withdrawal

Measure	Antibiotic Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Overall Study Could not be Contacted on Day 28	11	10
Overall Study Death	1	0
Overall Study Did not Receive Allocated Intervention	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.	Total n=245 Participants Total of all reporting groups
Age, Continuous	63 years n=5 Participants	62 years n=7 Participants	62.5 years n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	54 Participants n=7 Participants	106 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 28 days after surgery

Population: Intent-to-Treat (ITT) Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

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.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Experienced At Least One Postoperative Infectious Complication	13 Participants	8 Participants

PRIMARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

Surgical Site Infection:

1. 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

2. 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

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Experienced Surgical Site Infection	6 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

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

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Experienced Pneumonia	7 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

Empyema:

Positive pleural culture result or purulence within the thoracic space and leukocytosis or fever (>38°C).

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Experienced Empyema	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

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

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Experienced Clostridium (C) Difficile Colitis	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

The number of participants who needed any additional non-study antibiotics for any reason after randomization.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Received Additional Antibiotics for Any Reason Within 28 Days After Surgery	32 Participants	31 Participants

SECONDARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

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.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants Who Needed Reoperation	5 Participants	10 Participants

SECONDARY outcome

Timeframe: From day of surgery to discharge (up to 35 days)

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

The length of hospital stay is the number of days the participant remained in the hospital.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Length of Hospital Stay	3 days Interval 1.0 to 35.0	3 days Interval 0.0 to 31.0

SECONDARY outcome

Timeframe: From day of surgery to removal of chest tubes (up to 33 days)

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

Time to removal of chest tubes is the number of days from the time of chest tube placement to time they were removed.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Time to Removal of Chest Tubes	2 days Interval 0.0 to 32.0	2 days Interval 0.0 to 33.0

SECONDARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

The number of participants with an allergic reaction to a drug.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Number of Participants With Allergic Reactions	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 days after surgery

Population: ITT Population included all participants who were randomized and received their allocated intervention. 1 participant in the antibiotic arm and 2 participants in the placebo arm were randomized twice but are only counted once (per first randomization) in the ITT Population.

All-cause mortality is the number of deaths that occurred during the study period, regardless of the cause.

Outcome measures

Measure	Antibiotic n=121 Participants Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 Participants Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
All-Cause Mortality	1 Participants	0 Participants

Adverse Events

Antibiotic

Serious events: 1 serious events

Other events: 0 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Antibiotic n=121 participants at risk Cefazolin or vancomycin: 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 cephalosporin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.	Placebo n=124 participants at risk Placebo: Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.
Cardiac disorders Atrial fibrillation	0.83% 1/121 • From the time immediately following surgery up to 28 days.	0.00% 0/124 • From the time immediately following surgery up to 28 days.

Other adverse events

Adverse event data not reported

Additional Information

David Oxman, MD

Brigham & Women's Hospital

Phone: 215-503-1198

Email: doxman2001@yahoo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place