Topical Antibiotic Prophylaxis for Eyelids

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT03199911
• Collaborator: (none)
• Enrollment: 401
• Location: 1
• Arms: 2
• Actual Duration (Months): 25.4
• Patients Per Site Per Month: 15.8

Study Details

Study Description

Brief Summary

The investigators propose a prospective randomized control trial testing the hypothesis that routine topical antibiotic prophylaxis does not significantly reduce the rate of infection after eyelid surgery.

Condition or Disease	Intervention/Treatment	Phase
Antibiotic Side Effect; Eyelid; Wound; Eyelid Diseases; Surgical Wound Infection; Surgical Wound, Recent; Surgical Incision; Skin Cancer Face; Antibiotic Allergy; Surgical Site Infection	Drug: Topical Antibiotic Product; Drug: Topical Non-Antibiotic Ointment	Phase 4

Detailed Description

The use of prophylactic topical antibiotic therapy after eyelid surgery is widespread. Due to increasing antibiotic resistance, antibiotic-related complications, and healthcare costs, the investigators wish to determine whether prophylactic post-operative antibiotic ointment is truly necessary. After all, existing dermatology literature currently recommends against the routine use of antibiotic ointment after various surgical procedures (e.g. Mohs surgery). The investigators aim to perform a prospective randomized control trial at the University of California, San Francisco. The investigators aim to recruit a total of 400 oculoplastics patients undergoing eyelid surgery or surgery involving peri-orbital incisions from 2017 through 2019.

Study Design

• Study Type: Interventional
• Actual Enrollment: 401 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized to one of two intervention arms (i.e. antibiotic ointment vs. placebo artificial tear ointment) and will not at any point cross over to the other arm.Patients will be randomized to one of two intervention arms (i.e. antibiotic ointment vs. placebo artificial tear ointment) and will not at any point cross over to the other arm.
• Masking: None (Open Label)
• Masking Description: Randomization to one of two intervention arms (i.e. antibiotic ointment vs. placebo artificial tear ointment) will be performed prior to study recruitment by REDCap software. Patients' randomization assignments will be revealed at the initial pre-operative visit or at time that procedure consent is obtained; the study team will not be aware of a subject's randomization assignment prior to that time.
• Primary Purpose: Prevention
• Official Title: The Role of Topical Antibiotic Prophylaxis in Eyelid Surgery
• Actual Study Start Date: Oct 2, 2017
• Actual Primary Completion Date: Nov 14, 2019
• Actual Study Completion Date: Nov 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topical Antibiotic Ointment Intervention: 200 patients in the antibiotic arm will receive either erythromycin or bacitracin, based on allergies, surgeon preference, and antibiotic availability. If neither antibiotic is obtainable by the patient, bacitracin polymyxin will be prescribed instead. Antibiotic ointment is to be applied to the surgical incision(s) 4 times daily for 1 week.	Drug: Topical Antibiotic Product; Topical antibiotic ointment will be erythromycin or bacitracin. If the patient cannot obtain either (e.g. lack of availability at the pharmacy), bacitracin polymyxin will be prescribed. Allergy to all 3 study drugs means that a patient will be excluded from the study.; Other Names: Erythromycin, Bacitracin, Polysporin-Bacitracin
Placebo Comparator: Topical Non-Antibiotic Ointment Intervention: 200 patients in the placebo group will receive mineral oil/petrolatum-based artificial tear ointment to be applied to the surgical incision(s) 4 times daily for 1 week.	Drug: Topical Non-Antibiotic Ointment; Mineral oil/petrolatum-based artificial tear ointment.; Other Names: Refresh PM

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Surgical Site Infections [First Post-Operative Visit (~7-14 days)]

   The rate of superficial incisional or deep incisional surgical site infection (SSI) of clean and clean-contaminated wounds.

Secondary Outcome Measures

1. Number of High Risk Participants With Surgical Site Infections [First Post-Operative Visit (~7-14 days)]

   A secondary outcome is the rate of superficial or deep SSI in participants considered high risk for infection due to comorbidities such as smoking, exogenous immunosuppressive agent use, or medical conditions causing immunosuppression such as diabetes mellitus.

2. Number of Participants With Wound Dehiscence [First Post-Operative Visit (~7-14 days)]

   A secondary outcome recording the rate of wound dehiscence after surgery.

3. Number of Participants With Allergic Contact Dermatitis [First Post-Operative Visit (~7-14 days)]

   A secondary outcome recording the rate of allergic contact dermatitis due to post-operative ointment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Patients aged 18 and older who are undergoing various eyelid procedures in an office, ambulatory care center, or operating room including but not limited to:

• blepharoplasty (upper and lower lids);

• ectropion repair;

• entropion repair;

• external dacryocystorhinostomy;

• external levator resection;

• eyelid lesion removal and/or biopsy;

• eyelid reconstruction and defect repair including after Mohs surgery;

• fat pad excision (upper and lower lids);

• gold or platinum weight implantation;

• internal levator resection;

• lateral tarsal strip;

• orbital fracture repair requiring periorbital incisions;

• orbitotomy requiring periorbital incisions;

• tarsorrhaphy;

• wedge excision.

• Patients undergoing repeat procedures will also be included.

Exclusion Criteria:

• Patients aged younger than 18 years old who are undergoing the above eyelid procedures in an office, ambulatory care centers, operating rooms;

• patients undergoing chalazion removal;

• patients who have had previous wound infections at the site of the procedure;

• patients with oral or IV antibiotic use within 10 days prior to procedure;

• patients requiring IV antibiotics during the procedure;

• patients with grossly contaminated or inflamed wounds;

• patients with human or animal bites, patients with wounds resulting from trauma

• patients allergic to all study drug options.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Robert Kersten, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol - Sep 9, 2018
• Statistical Analysis Plan - Apr 1, 2020

More Information

Publications

• Carter SR, Stewart JM, Khan J, Archer KF, Holds JB, Seiff SR, Dailey RA. Infection after blepharoplasty with and without carbon dioxide laser resurfacing. Ophthalmology. 2003 Jul;110(7):1430-2.
• Fay A, Nallasamy N, Bernardini F, Wladis EJ, Durand ML, Devoto MH, Meyer D, Hartstein M, Honavar S, Osaki MH, Osaki TH, Santiago YM, Sales-Sanz M, Vadala G, Verity D. Multinational Comparison of Prophylactic Antibiotic Use for Eyelid Surgery. JAMA Ophthalmol. 2015 Jul;133(7):778-84. doi: 10.1001/jamaophthalmol.2015.0789.
• Ferneini EM, Halepas S, Aronin SI. Antibiotic Prophylaxis in Blepharoplasty: Review of the Current Literature. J Oral Maxillofac Surg. 2017 Jul;75(7):1477-1481. doi: 10.1016/j.joms.2017.01.025. Epub 2017 Feb 1. Review.
• Levender MM, Davis SA, Kwatra SG, Williford PM, Feldman SR. Use of topical antibiotics as prophylaxis in clean dermatologic procedures. J Am Acad Dermatol. 2012 Mar;66(3):445-51. doi: 10.1016/j.jaad.2011.02.005. Epub 2011 Aug 6.
• Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999 Apr;20(4):250-78; quiz 279-80.
• Rogers HD, Desciak EB, Marcus RP, Wang S, MacKay-Wiggan J, Eliezri YD. Prospective study of wound infections in Mohs micrographic surgery using clean surgical technique in the absence of prophylactic antibiotics. J Am Acad Dermatol. 2010 Nov;63(5):842-51. doi: 10.1016/j.jaad.2010.07.029. Epub 2010 Aug 30.
• Saco M, Howe N, Nathoo R, Cherpelis B. Topical antibiotic prophylaxis for prevention of surgical wound infections from dermatologic procedures: a systematic review and meta-analysis. J Dermatolog Treat. 2015 Apr;26(2):151-8. doi: 10.3109/09546634.2014.906547. Epub 2014 Apr 8. Review.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03199911
• Other Study ID Numbers: 17-22309
• First Posted: Jun 27, 2017
• Last Update Posted: Jul 21, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Surgical Wound Infection; Wound Infection; Eyelid Diseases; Wounds and Injuries; Surgical Wound; Anti-Bacterial Agents; Erythromycin; Bacitracin

Study Results

Participant Flow

Arm/Group Title	Topical Antibiotic Ointment	Topical Non-Antibiotic Ointment
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.	The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.
Period Title: Overall Study
STARTED	208	193
Did Not Proceed With Surgery	2	1
Received Allocated Treatment	206	192
Lost to Follow-up	5	5
Primary Outcome Analyzed	201	187
COMPLETED	201	187
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	Topical Antibiotic Ointment	Topical Non-Antibiotic Ointment	Total
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.	The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.	Total of all reporting groups
Overall Participants	206	192	398
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (16.7)	63.4 (15.4)	63.5 (16.0)
Sex: Female, Male (Count of Participants)
Female	127 61.7%	112 58.3%	239 60.1%
Male	79 38.3%	80 41.7%	159 39.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 8.3%	12 6.3%	29 7.3%
Not Hispanic or Latino	189 91.7%	179 93.2%	368 92.5%
Unknown or Not Reported	0 0%	1 0.5%	1 0.3%
Smoking status (Count of Participants)
Yes	18 8.7%	13 6.8%	31 7.8%
No	188 91.3%	178 92.7%	366 92%
Unknown	0 0%	1 0.5%	1 0.3%
High risk for infection (Count of Participants)
Yes	44 21.4%	47 24.5%	91 22.9%
No	162 78.6%	145 75.5%	307 77.1%
Asplenia (Count of Participants)
Yes	1 0.5%	0 0%	1 0.3%
No	205 99.5%	192 100%	397 99.7%
Autoimmune disease (Count of Participants)
Yes	6 2.9%	2 1%	8 2%
No	200 97.1%	190 99%	390 98%
Diabetes mellitus (Count of Participants)
Yes	24 11.7%	31 16.1%	55 13.8%
No	182 88.3%	161 83.9%	343 86.2%
Human immunodeficiency virus infection (Count of Participants)
Yes	0 0%	4 2.1%	4 1%
No	206 100%	188 97.9%	394 99%
Malignancy (Count of Participants)
Yes	0 0%	2 1%	2 0.5%
No	206 100%	190 99%	396 99.5%
Organ transplantation (Count of Participants)
Yes	0 0%	1 0.5%	1 0.3%
No	206 100%	191 99.5%	397 99.7%
Blepharoplasty (Count of Participants)
Yes	48 23.3%	39 20.3%	87 21.9%
No	158 76.7%	153 79.7%	311 78.1%
Browplasty (Count of Participants)
Yes	3 1.5%	0 0%	3 0.8%
No	203 98.5%	192 100%	395 99.2%
Dacryocystorhinostomy (Count of Participants)
Yes	1 0.5%	6 3.1%	7 1.8%
No	205 99.5%	186 96.9%	391 98.2%
Ectropion/Entropion repair (Count of Participants)
Yes	25 12.1%	25 13%	50 12.6%
No	181 87.9%	167 87%	348 87.4%
Eyelid lesion removal and/or biopsy (Count of Participants)
Yes	36 17.5%	36 18.8%	72 18.1%
No	170 82.5%	156 81.3%	326 81.9%
Ptosis repair (Count of Participants)
Yes	41 19.9%	43 22.4%	84 21.1%
No	165 80.1%	149 77.6%	314 78.9%
Reconstruction after Mohs surgery (Count of Participants)
Yes	25 12.1%	22 11.5%	47 11.8%
No	181 87.9%	170 88.5%	351 88.2%
Orbitotomy (Count of Participants)
Yes	8 3.9%	11 5.7%	19 4.8%
No	198 96.1%	181 94.3%	379 95.2%
Tarsorrhaphy (Count of Participants)
Yes	3 1.5%	1 0.5%	4 1%
No	203 98.5%	191 99.5%	394 99%
Wedge excision (Count of Participants)
Yes	15 7.3%	15 7.8%	30 7.5%
No	191 92.7%	177 92.2%	368 92.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Surgical Site Infections
Description	The rate of superficial incisional or deep incisional surgical site infection (SSI) of clean and clean-contaminated wounds.
Time Frame	First Post-Operative Visit (~7-14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Antibiotic Ointment	Topical Non-Antibiotic Ointment
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.	The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.
Measure Participants	201	187
Count of Participants [Participants]	0 0%	5 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topical Antibiotic Ointment, Topical Non-Antibiotic Ointment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of High Risk Participants With Surgical Site Infections
Description	A secondary outcome is the rate of superficial or deep SSI in participants considered high risk for infection due to comorbidities such as smoking, exogenous immunosuppressive agent use, or medical conditions causing immunosuppression such as diabetes mellitus.
Time Frame	First Post-Operative Visit (~7-14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Antibiotic Ointment	Topical Non-Antibiotic Ointment
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.	The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.
Measure Participants	44	47
Count of Participants [Participants]	0 0%	1 0.5%

3. Secondary Outcome

Title	Number of Participants With Wound Dehiscence
Description	A secondary outcome recording the rate of wound dehiscence after surgery.
Time Frame	First Post-Operative Visit (~7-14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Antibiotic Ointment	Topical Non-Antibiotic Ointment
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.	The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.
Measure Participants	201	187
Count of Participants [Participants]	7 3.4%	5 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topical Antibiotic Ointment, Topical Non-Antibiotic Ointment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.42 to 4.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With Allergic Contact Dermatitis
Description	A secondary outcome recording the rate of allergic contact dermatitis due to post-operative ointment.
Time Frame	First Post-Operative Visit (~7-14 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topical Antibiotic Ointment	Topical Non-Antibiotic Ointment
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.	The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.
Measure Participants	201	187
Count of Participants [Participants]	1 0.5%	1 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Topical Antibiotic Ointment, Topical Non-Antibiotic Ointment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.06 to 14.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected until the final post-operative visit (approximately 3 months).
Adverse Event Reporting Description	Among participants who did not proceed with surgery or who had no post-operative follow-up, adverse event data for events specific to the post-operative period (i.e. allergic contact dermatitis or wound dehiscence) were not collected. These participants were excluded from the denominator in determining frequency of these adverse events.
Arm/Group Title	Topical Antibiotic Ointment		Topical Non-Antibiotic Ointment
Arm/Group Description	The antibiotic arm received either erythromycin or a bacitracin containing ointment, depending on allergies, surgeon preference, and pharmacy availability. Patients were instructed to apply the ointment to the surgical incision(s) 4 times daily for 1 week.		The non-antibiotic ointment arm received mineral oil/petrolatum-based artificial tear ointment with instructions to apply it to the surgical incision(s) 4 times daily for 1 week.
All Cause Mortality
	Topical Antibiotic Ointment		Topical Non-Antibiotic Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/208 (0%)		0/193 (0%)
Serious Adverse Events
	Topical Antibiotic Ointment		Topical Non-Antibiotic Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/208 (0%)		0/193 (0%)
Other (Not Including Serious) Adverse Events
	Topical Antibiotic Ointment		Topical Non-Antibiotic Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/208 (3.8%)		6/193 (3.1%)
Skin and subcutaneous tissue disorders
Allergic contact dermatitis	1/201 (0.5%)	1	1/187 (0.5%)	1
Wound dehiscence	7/201 (3.5%)	7	5/187 (2.7%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.