Antibiotic Prophylaxis in Orthopaedic Traumatology

• Sponsor: University of Missouri-Columbia (Other)
• Overall Status: Completed
• CT.gov ID: NCT00610987
• Collaborator: (none)
• Enrollment: 178
• Location: 1
• Arms: 2
• Duration (Months): 72
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

It has been established that providing antibiotic prophylaxis after closed fracture fixation with implants or prosthetic devices has beneficial effects. However, the optimal duration of antibiotic prophylaxis after orthopaedic trauma surgery is not well-defined. Most studies comparing single-dose prophylaxis with multiple-dose prophylaxis have not shown beneficial effects of additional doses. Our proposed study is intended to further define the appropriate duration of antibiotic (cefazolin) administration for surgical prophylaxis in the treatment of closed fractures. We will randomly assigned patients into two groups, hopefully differentiated only by the duration of antibiotic administration (single dose vs. 24 hours). We will follow these patients until fracture healing and determine if there is a difference in the incidence of infection.

Condition or Disease	Intervention/Treatment	Phase
Fractures, Closed; Wounds and Injuries	Drug: cefazolin; Drug: Placebo	N/A

Detailed Description

The proposed study is a prospective, randomized, double-blinded clinical trial intended to further define the appropriate duration of antibiotic (cefazolin) administration for surgical prophylaxis in the internal fixation of closed fractures. Our hypothesis is that there will be no difference in the incidence of infection between single-dose versus 24 hours of antibiotic prophylaxis. The null hypothesis is that multiple-dose antibiotic prophylaxis will have a decreased incidence of infection.

Research Design:

A prospective, randomized, double-blinded clinical trial will be conducted to evaluate the duration of antibiotic prophylaxis. After investigators obtain Institutional Review Board approval, recruited patients will be randomly assigned to one of two groups. Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. If a tourniquet is used, the cefazolin will be administered at least 10 minutes prior to inflation. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours. Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo. Group assignments will not be disclosed to the evaluators responsible for clinical examination or to the patients until the end of the study.

Either an orthopaedic surgeon or nurse practitioner will evaluate the patients for the development of a wound infection. Follow-up will occur at 10-14 days, six weeks, 12 weeks, and every six to eight weeks thereafter until bony union occurs. Wound infection will be defined as one or more of the classic signs and symptoms of inflammation (rubor, calor, tumor, dolor) together with purulent drainage at the operative site. Wound infections will be classified either as superficial (infection of the skin or subcutaneous tissue, not communicating with the bone) or deep (infection that reached bone or material implanted for osteosynthesis). Bacteriological cultures will be obtained in the event of infectious complications, but wound infections will be diagnosed clinically.

Several studies have demonstrated that there are numerous patient-related and treatment-related factors that predispose to infectious complications. We will use several of these factors to assign a risk score to each of the enrolled patients. Each factor will be worth one point for a total score ranging from 0 (lowest risk) to 7 (highest risk). The risk factors are: 1) smoking; 2) age >65; 3) diabetes mellitus; 4) obesity (BMI >35); 5) duration of surgery >3 hours; 6) urinary catheterization (0=no catheter, 1=catheter <48 hours, 2=catheter >48 hours).

Statistical evaluation will be conducted by Student's t-test for patient characteristics and chi square analysis for infection rates. The relation between wound infection and the various possible risk factors will be assessed by forward stepwise logistic regression analysis. Significance will be defined at the P < 0.05 level.

Study Design

• Study Type: Interventional
• Actual Enrollment: 178 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Antibiotic Prophylaxis in Orthopaedic Traumatology: A Prospective, Randomized Trial of Duration of Administration
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cefazolin Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours after surgical repair of the closed limb fracture.	Drug: cefazolin; Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours.; Other Names: cefazolin brand name = Kefzol
Placebo Comparator: Placebo Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo, after the intraoperative dose(s) of cefazolin	Drug: Placebo; Patients will be randomly assigned to one of two groups. Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Total Wound Infections [at 10-14 days, six weeks, 12 weeks, and every six to eight weeks thereafter until bony union occurs.]

   The primary endpoint was infection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients 18 years or older;

• Scheduled for primary osteosynthesis or placement of a prosthetic device in the treatment of closed limb fractures;

• Ability to give informed consent.

Exclusion Criteria:

• Known hypersensitivity to cephalosporins;

• Antimicrobial use or symptoms of infection in the week before surgery;

• Pregnancy;

• Immunosuppressive treatment;

• Inability to give informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Missouri	Columbia	Missouri	United States	65212

Sponsors and Collaborators

• University of Missouri-Columbia

Investigators

• Principal Investigator: Brett D Crist, MD, University of Missouri-Columbia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Brett Crist, Assistant Professor, Co-Director of Trauma Services, Co-Director Trauma Fellowship, Department of Orthopaedic Surgery, University of Missouri-Columbia
• ClinicalTrials.gov Identifier: NCT00610987
• Other Study ID Numbers: IRB1089017
• First Posted: Feb 8, 2008
• Last Update Posted: Jun 12, 2015
• Last Verified: May 1, 2015

• Keywords provided by Brett Crist, Assistant Professor, Co-Director of Trauma Services, Co-Director Trauma Fellowship, Department of Orthopaedic Surgery, University of Missouri-Columbia: Antibiotic Prophylaxis
• Additional relevant MeSH terms: Wounds and Injuries; Fractures, Closed; Cefazolin

Study Results

Participant Flow

Recruitment Details	After IRB approval, patients undergoing ORIF of closed fractures that had a planned postoperative stay of at least 23 hours were randomized to either receiving 23 hours of cefazolin or a placebo.
Pre-assignment Detail	After IRB approval, patients undergoing ORIF of closed fractures that had a planned postoperative stay of at least 23 hours were randomized to either receiving 23 hours of cefazolin or a placebo.

Arm/Group Title	Cefazolin	Placebo
Arm/Group Description	Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours after surgical repair of the closed limb fracture. cefazolin: Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours.	Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo, after the intraoperative dose(s) of cefazolin Placebo: Patients will be randomly assigned to one of two groups. Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo.
Period Title: Overall Study
STARTED	75	71
COMPLETED	75	71
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cefazolin	Placebo	Total
Arm/Group Description	Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours after surgical repair of the closed limb fracture. cefazolin: Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours.	Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo, after the intraoperative dose(s) of cefazolin Placebo: Patients will be randomly assigned to one of two groups. Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo.	Total of all reporting groups
Overall Participants	75	71	146
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	55 73.3%	37 52.1%	92 63%
>=65 years	20 26.7%	34 47.9%	54 37%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.9 (19.1)	50.5 (20.5)	49.8 (19.9)
Sex: Female, Male (Count of Participants)
Female	30 40%	39 54.9%	69 47.3%
Male	45 60%	32 45.1%	77 52.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Total Wound Infections
Description	The primary endpoint was infection.
Time Frame	at 10-14 days, six weeks, 12 weeks, and every six to eight weeks thereafter until bony union occurs.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cefazolin	Placebo
Arm/Group Description	Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours after surgical repair of the closed limb fracture. cefazolin: Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours.	Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo, after the intraoperative dose(s) of cefazolin Placebo: Patients will be randomly assigned to one of two groups. Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo.
Measure Participants	75	71
Number [participants]	4 5.3%	9 12.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefazolin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.12
	Comments
	Method	t-test, 1 sided
	Comments

Adverse Events

Arm/Group Title	Cefazolin		Placebo
Arm/Group Description	Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours after surgical repair of the closed limb fracture. cefazolin: Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group I will receive 1-g doses of cefazolin every eight hours for the next 24 hours.		Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo, after the intraoperative dose(s) of cefazolin Placebo: Patients will be randomly assigned to one of two groups. Both groups will receive 1 gram (g) of IV cefazolin prior to incision, per standard protocol at our institution. A 2-g dose of cefazolin will be administered IV for patients weighing more than 80 kg. A second 1-g dose of cefazolin will be given three hours later if the patient is still in the operating room. Upon completion of the surgical procedure, Group II will receive no additional antibiotic. Instead, they will receive normal saline injection every eight hours as a placebo.
All Cause Mortality
	Cefazolin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cefazolin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/75 (24%)		22/71 (31%)
General disorders
General disorders including death	1/75 (1.3%)	1	8/71 (11.3%)	8
Infections and infestations
Infections	15/75 (20%)	15	5/71 (7%)	5
Injury, poisoning and procedural complications
trauma	1/75 (1.3%)	1	2/71 (2.8%)	2
Renal and urinary disorders
Urinary tract infection	0/75 (0%)	0	3/71 (4.2%)	3
Surgical and medical procedures
implant problems	1/75 (1.3%)	1	2/71 (2.8%)	2
Vascular disorders
vascular	0/75 (0%)	0	2/71 (2.8%)	2
Other (Not Including Serious) Adverse Events
	Cefazolin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/71 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.