SSI Rates in Patients Undergoing Mastectomy Without Reconstruction- A Multicenter, Double-blinded RCT.

Surgical Site Infection Clinical Trial

Official title:

Surgical Site Infection (SSI) Rates in Patients Undergoing Mastectomy Without Reconstruction, a Comparison Among Those Receiving Preoperative Prophylactic Antibiotics Alone Versus Continued Prophylactic Antibiotics Postoperatively-A Multicenter, Double-blinded Randomized Control Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04577846
• Other study ID #: 2020-3627-1407
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: October 2020
• Source: Aga Khan University
• Contact: Abida K. Sattar, MD, FACS
• Phone: +92 345 8298088
• Email: aksattar[@]hotmail.com; abida.sattar[@]aku.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Breast cancer is the second most prevalent malignancy in the world and an important component of treatment warrants surgical procedures such as mastectomy. Surgical site infections after breast surgery may range from 1-26%, which is high for surgeries that are considered "clean procedures", as defined by the Centers for Disease Control and Prevention (CDC) wound classification system.

Prophylactic antibiotics given before the surgical incision as per Joint Commissions SCIP (Surgical Care Improvement Project) guidelines, have been shown to decrease the rate of postoperative infections in a vast number of patients. There is however, no clear consensus due to lack of evidence on continuation (duration) of prophylactic antibiotics in patients undergoing mastectomy with indwelling drains, and thus antibiotic prescribing practices may vary among breast as well as reconstructive surgeons.

In this trial all patients undergoing mastectomy without immediate reconstruction will receive a single prophylactic dose of preoperative antibiotic, and subsequently, the patients will be randomized to either continue the prophylactic antibiotics or receive a placebo for the duration of indwelling drains. The aim of this trial is to compare the difference in SSI rates between these two study arms as the main outcome. In addition, the factors associated with differing rates of SSI in the intervention and control group will also be identified.

Description:

Introduction:

Worldwide, breast cancer comprises 10.4% of all cancer among women, making it the second most common cancer (after lung cancer) and the fifth most common cause of cancer related death. The management of patients as a matter of patient preference or as dictated by extent of disease often warrants a mastectomy.

Reports of surgical site infections after breast surgery including mastectomy may range from 1-26%, which is high for surgeries that are considered "clean procedures". Despite a high rate of surgical site infections, there is no consensus on the continuation/duration of prophylactic antibiotics in patients undergoing mastectomy. Consequently, practices may vary among breast and reconstructive surgeons. Evidence regarding the risk of SSI with the use and duration of indwelling drains is also controversial. The length of prolonged, postoperative antibiotic may also vary by practitioners, some using a pre-defined regimen of about 2-7 days, and others continuing them until the drains are removed.

Most guidelines recommend a single dose of pre-operative antibiotics and continuation after surgery has been discouraged. The use of common or more specific antibiotics for the duration of drains being in place is also controversial. The recommendation by recent national clinical guidelines is to use one dose of pre-procedural antibiotics for mastectomy patients with or without drains. The American Society of Breast Surgeons also does not recommend the continuation of post-surgical antibiotics in the absence of relevant indications. However, practices vary.

Rationale:

Since there is lack of evidence and significant surgeon practice variation despite guidelines developed by leading societies, we propose to study the difference in rates of surgical site infection (SSI) with or without continuation of prolonged post-operative, prophylactic antibiotics in all patients undergoing mastectomy without immediate reconstruction and with indwelling drains.

Aim:

In this trial all patients undergoing mastectomy without immediate reconstruction will receive a single prophylactic dose of preoperative antibiotic, and subsequently, the patients will be randomized to either continue the prophylactic antibiotics or receive a placebo for the duration of indwelling drains. The aim of this trial is to compare the difference in SSI rates between these two study arms as the main outcome. In addition, the factors associated with differing rates of SSI in the intervention and control group will also be identified.

Significance:

Through this study, the investigators will be able to identify the most effective prophylactic regimen to reduce rates of SSI among mastectomy patients with indwelling drains leading to evidence-based and informed decision making.

Primary Objective:

To determine rates of surgical site infection (SSI) in patients in two separate arms of this trial, in which all patients will receive the first prophylactic pre/perioperative antibiotic dose and then be randomized to:

1. Post-operative antibiotic prophylaxis continued for the duration of indwelling drains

2. Those who only receive a single dose of preoperative prophylactic antibiotic.

Secondary Objective:

To identify factors associated with differing rates of SSI in the intervention and control group

Primary Outcome:

Surgical site infection(SSI) rates at the mastectomy wound site or the drain(s) insertion site among patients. In this study SSI will be evaluated using the standard CDC criteria which are as follows:

1. purulent drainage from the incision or drain site;

2. organisms isolated from an aseptically obtained culture of fluid or tissue;

3. deliberate opening of the incision by a surgeon in patients having either tenderness, localized swelling, redness, or warmth; or

4. diagnosis of SSI by the surgeon or study wound assessor (trained research assistant) or

5. prescription of therapeutic antibiotics;

6. Patients clinically diagnosed and documented to have cellulitis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 384
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Patients who will undergo mastectomy (without immediate reconstruction) at AKUH, LNH, and DUHS (with or without axillary surgery), who will have indwelling closed suction drain(s) postoperatively and will give consent to participate in the study

Exclusion Criteria:

• Undergo breast reconstruction

• Who have other medical indications for which they must remain on antibiotics for more than the single preoperative dose

• Those with any history of allergies to beta-lactam drug

• Patients who had an open breast or axillary biopsy/breast conservation in the last 30 days on the ipsilateral side.

Related Conditions & MeSH terms

• Infection
• Surgical Site Infection
• Surgical Wound Infection

Intervention

Drug:
• Cephalexin 500 MG
Cefalexin 500 mg PO q8 hours will be continued for the duration of the indwelling drains which usually is about 14 days.
• Placebo
A placebo capsule filled with inert material for the duration of the drains which usually is about 14 days.

Locations

Country	Name	City	State
Pakistan	Aga Khan University Hospital	Karachi	Sindh
Pakistan	Dow University of Health Sciences	Karachi	Sindh
Pakistan	Liaquat National Hospital	Karachi	Sindh

Sponsors (3)

Lead Sponsor	Collaborator
Aga Khan University	Dow University of Health Sciences, Liaquat National Hospital & Medical College

Country where clinical trial is conducted

Pakistan, 

References & Publications (19)

Angarita FA, Acuna SA, Torregrosa L, Tawil M, Escallon J, Ruíz Á. Perioperative variables associated with surgical site infection in breast cancer surgery. J Hosp Infect. 2011 Dec;79(4):328-32. doi: 10.1016/j.jhin.2011.08.006. Epub 2011 Nov 3. — View Citation

Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA; American Society of Health-System Pharmacists (ASHP); Infectious Diseases Society of America (IDSA); Surgical Infection Society (SIS); Society for Healthcare Epidemiology of America (SHEA). Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt). 2013 Feb;14(1):73-156. doi: 10.1089/sur.2013.9999. Epub 2013 Mar 5. — View Citation

Degnim AC, Scow JS, Hoskin TL, Miller JP, Loprinzi M, Boughey JC, Jakub JW, Throckmorton A, Patel R, Baddour LM. Randomized controlled trial to reduce bacterial colonization of surgical drains after breast and axillary operations. Ann Surg. 2013 Aug;258(2):240-7. doi: 10.1097/SLA.0b013e31828c0b85. — View Citation

Edwards BL, Stukenborg GJ, Brenin DR, Schroen AT. Use of prophylactic postoperative antibiotics during surgical drain presence following mastectomy. Ann Surg Oncol. 2014 Oct;21(10):3249-55. doi: 10.1245/s10434-014-3960-7. Epub 2014 Aug 20. — View Citation

Felippe WA, Werneck GL, Santoro-Lopes G. Surgical site infection among women discharged with a drain in situ after breast cancer surgery. World J Surg. 2007 Dec;31(12):2293-9; discussion 2300-1. — View Citation

Gao YX, Xu L, Ye JM, Wang DM, Zhao JX, Zhang LB, Duan XN, Liu YH. Analysis of risk factors of surgical site infections in breast cancer. Chin Med J (Engl). 2010 Mar 5;123(5):559-62. — View Citation

Hedrick TL, Smith PW, Gazoni LM, Sawyer RG. The appropriate use of antibiotics in surgery: a review of surgical infections. Curr Probl Surg. 2007 Oct;44(10):635-75. Review. — View Citation

Jones DJ, Bunn F, Bell-Syer SV. Prophylactic antibiotics to prevent surgical site infection after breast cancer surgery. Cochrane Database Syst Rev. 2014 Mar 9;(3):CD005360. doi: 10.1002/14651858.CD005360.pub4. Review. Update in: Cochrane Database Syst Rev. 2019 Sep 26;9:CD005360. — View Citation

Rey JE, Gardner SM, Cushing RD. Determinants of surgical site infection after breast biopsy. Am J Infect Control. 2005 Mar;33(2):126-9. — View Citation

Rotstein C, Ferguson R, Cummings KM, Piedmonte MR, Lucey J, Banish A. Determinants of clean surgical wound infections for breast procedures at an oncology center. Infect Control Hosp Epidemiol. 1992 Apr;13(4):207-14. — View Citation

Teija-Kaisa A, Eija M, Marja S, Outi L. Risk factors for surgical site infection in breast surgery. J Clin Nurs. 2013 Apr;22(7-8):948-57. doi: 10.1111/jocn.12009. Epub 2012 Nov 2. Erratum in: J Clin Nurs. 2015 Oct;24(19-20):3020. — View Citation

Thomas C, Stevenson M, Riley TV. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. J Antimicrob Chemother. 2003 Jun;51(6):1339-50. Epub 2003 May 13. Review. — View Citation

Thomson DR, Sadideen H, Furniss D. Wound drainage after axillary dissection for carcinoma of the breast. Cochrane Database Syst Rev. 2013 Oct 20;(10):CD006823. doi: 10.1002/14651858.CD006823.pub2. Review. — View Citation

Throckmorton AD, Boughey JC, Boostrom SY, Holifield AC, Stobbs MM, Hoskin T, Baddour LM, Degnim AC. Postoperative prophylactic antibiotics and surgical site infection rates in breast surgery patients. Ann Surg Oncol. 2009 Sep;16(9):2464-9. doi: 10.1245/s10434-009-0542-1. Epub 2009 Jun 9. — View Citation

Vilar-Compte D, Jacquemin B, Robles-Vidal C, Volkow P. Surgical site infections in breast surgery: case-control study. World J Surg. 2004 Mar;28(3):242-6. Epub 2004 Feb 17. — View Citation

Vilar-Compte D, Rosales S, Hernandez-Mello N, Maafs E, Volkow P. Surveillance, control, and prevention of surgical site infections in breast cancer surgery: a 5-year experience. Am J Infect Control. 2009 Oct;37(8):674-9. doi: 10.1016/j.ajic.2009.02.010. Epub 2009 Jun 24. — View Citation

Wilcox MH, Chalmers JD, Nord CE, Freeman J, Bouza E. Role of cephalosporins in the era of Clostridium difficile infection. J Antimicrob Chemother. 2017 Jan;72(1):1-18. Epub 2016 Sep 22. Review. — View Citation

Wilcox MH, Mooney L, Bendall R, Settle CD, Fawley WN. A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother. 2008 Aug;62(2):388-96. doi: 10.1093/jac/dkn163. Epub 2008 Apr 22. — View Citation

Zeeshan S, Ali B, Ahmad K, Chagpar AB, Sattar AK. Clinicopathological Features of Young Versus Older Patients With Breast Cancer at a Single Pakistani Institution and a Comparison With a National US Database. J Glob Oncol. 2019 Mar;5:1-6. doi: 10.1200/JGO.18.00208. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rates of antibiotic associated side-effects	infections/diarrhea/other side effects	will be assessed during the follow-up visits between postoperative days 4-8 days for the 1st postoperative visit and subsequently at each routine postoperative visit while the drain is in place, for a maximum of 30 days.
Primary	Surgical Site Infection (SSI)	Standard CDC criteria: purulent drainage from the incision or drain site; organisms isolated from an aseptically obtained culture of fluid or tissue; deliberate opening of the incision by a surgeon in patients having either tenderness, localized swelling, redness, or warmth; or; diagnosis of SSI by the surgeon or study wound assessor or; prescription of therapeutic antibiotics; Patients clinically diagnosed and documented to have cellulitis.	up to 30 days.

External Links

•   An Updated Meta-Analysis on the Effectiveness of Preoperative Prophylactic Antibiotics in Patients Undergoing Breast Surgical Procedures
•   National Practice Patterns in Preoperative and Postoperative Antibiotic Prophylaxis in Breast Procedures Requiring Drains: Survey of the American Society of Breast Surgeons
•   Specifications Manual for Joint Commission National Quality Core Measures