Bowel Preparation in Elective Pediatric Colorectal Surgery

Inflammatory Bowel Diseases Clinical Trial

Official title:

Pre-Operative Mechanical Bowel Preparation And Prophylactic Oral Antibiotics For Pediatric Patients Undergoing Elective Colorectal Surgery: A Feasibility Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03593252
• Other study ID #: Bowel_prep_pediatric_sx
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: January 30, 2024

Study information

• Verified date: November 2021
• Source: McMaster University
• Contact: Daniel Briatico, MSc
• Phone: 905-521-2100
• Email: briaticd[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Infections after elective intestinal surgery remain a significant burden for patients and for the health care system. The cost of treating a single surgical site infection is estimated at approximately $27,000. In adult patients, there is good evidence that the combination of oral antibiotics and mechanical bowel preparation is effective at reducing infections after intestinal surgery. In children, the body of evidence is much weaker. In this population, little evidence exists for oral antibiotics reducing infections and no data exists as to the effect of combining antibiotics with mechanical bowel preparation (such as polyethylene glycol (PEG)). The goal of the proposed study is to examine the effects of oral antibiotics with and without the combined use of mechanical bowel preparation on the rate of post-operative infectious complications in children aged 6 months to 18 years. This will be compared to the institution's current standard of care, which is to abstain from any type of mechanical bowel preparations or oral antibiotic administration before intestinal surgery.

Description:

Background: A Cochrane review of randomized controlled trials of MBP use in adults showed no difference in the rate of wound infection or anastomotic leak in colon or rectal procedures with MBP compared to no preparation (Guenaga, Matos, & Wille-Jorgensen, 2011). Two recent systematic reviews and meta-analyses support those findings. Lok and colleagues (2018) identified two randomized controlled trials and four retrospective reviews for patient <21 years, looking at preoperative MBP and its effect on the incidence postoperative complications, including anastomotic leak, wound infection, and intra-abdominal infection (Janssen Lok M 2018). Overall, MBP before colorectal surgery did not significantly decrease the incidence of post-operative outcomes. This was consistent with findings from a systematic review in mechanical bowel preparation in pediatric population. The review showed that the risk of developing a post-operative infection was 10.1% in patients who received MBP compared to 9.1% in patients who did not receive MBP, resulting in no statistically significant difference difference (risk difference of -0.03% (95% CI, -0.09% - 0.03%)) (Zwart 2018). With regards to OA alone, the adult literature showed promising results in favour of the OA. In a Cochrane review on antimicrobial prophylaxis in colorectal surgery, the addition of OA to the intravenous antibiotics was found to reduce surgical wound infection (RR 0.56, 95% CI 0.43 to 0.74) (Nelson, Gladman, & Barbateskovic, 2014). There are fewer studies in the pediatric population on the subject, they contain fewer patients and are mainly retrospective in nature. In a multi-center retrospective study, Serrurier et al. (2012), reviewed outcomes in children who underwent colostomy closure, and found higher rates of wound infection (14% vs. 6%, p=0.04) and a longer hospital length of stay in children who received MBP. In a retrospective cohort study including 1581 pediatric patients from PHIS database, post-operative complications were found to be highest in the no preparation group compared to combination prep and OA alone (23.3%, 15.9%, and 14.2% respectively; p=0.002) (Ares 2018). One study compared MBP alone versus MBP with OA in children undergoing colostomy closure post anorectal malformation repair and found no difference in overall SSI rates (MBP+OA: 13% (7/53) versus MBP alone: 17% (7/12) p=0.64) (Breckler, Rescorla, & Billmire, 2010). The authors found that the use of MBP alone was associated with a greater risk of wound infection (14% vs. 6%, p=0.04) and a longer hospital stay. Evidence to support the sole use of oral antibiotics versus in combination with MBP is lacking, particularly in the pediatric literature, with more studies being required to address this question. One recent meta-analysis including adults assessed 8458 adult patients (38 clinical trials), comparing 4 groups of different bowel preparation: MBP with OA, OA only, MBP only, and no preparation. The primary outcome was the total rate of incisional and organ/space SSIs. Results showed that only MBP with OA versus MBP alone was associated with a statistically significant reduction in SSI rates. The use of OA without MBP was not associated with a statistically significant reduction in SSI rates when compared to any other group. The authors concluded that MBP with OA was associated with the lowest risk of SSI, followed by OA only (Toh et al., 2018). It remains unclear whether the addition of MBP to OA in pediatric population affects the rate of post-operative infectious complications positively or negatively. The current study is therefore needed to build on the work conducted in the adult literature to determine best practices for the pediatric population. Purpose: This is a pilot study to check the feasibility of conducting a randomized controlled trial to assess the efficacy of oral nonabsorbable antibiotics, with or without mechanical bowel preparation, in reducing the rate of post-operative infectious complications occurring within 30 days post-operatively in children and adolescents (aged 6 months to 18 years) undergoing elective colon or rectal surgery. Post-operative complications include: surgical site infections (incisional, organ-space, and anatomic leak), length of hospital stay, readmission, post-operative use of therapeutic antibiotics, re-operation, occurrence of electrolyte disturbances (in case MBP was used), and occurrence of C. difficile infection.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 81
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 18 Years

Eligibility

Inclusion Criteria:

1. Pediatric patients aged three months to eighteen years being treated by the Pediatric General Surgery service at McMaster Children's Hospital.

2. Undergoing elective colorectal surgery.

3. Parents or legal guardian able to give free and informed consent.

Exclusion Criteria:

1. Non-elective surgery

2. Procedures that would not require mechanical bowel preparation:

1. Colorectal resection with an existing diverting small bowel ostomy.

2. Completion proctectomy - Ileal Pouch Anal Anasotmosis (IPAA)

3. Closure of small bowel ostomy (e.g. ileostomy)

3. Mechanical bowel obstruction

4. Known hypersensitivity to laxatives or oral antibiotics (neomycin and metronidazole)

5. Contraindication to oral antibiotics

6. Patients on long-term antibiotics for other reasons

7. Congestive heart failure

8. Renal insufficiency

9. Other medical conditions precluding the use of either oral antibiotics or mechanical bowel preparation

10. Co-enrolment in another intervention trial

Related Conditions & MeSH terms

• Bowel Obstruction
• Colostomy
• Elective Surgery
• Enterocolitis
• Enterocolitis, Necrotizing
• Hirschsprung Disease
• Inflammatory Bowel Diseases
• Intestinal Obstruction
• Meconium Ileus
• Necrotizing Enterocolitis

Intervention

Drug:
• Senna
Laxative,used for bowel preparation
• Sodium Picosulfate, Magnesium Oxide and Citric Acid
Laxative used for bowel preparation
• Metronidazole Oral
Oral antibiotic
• Neomycin
Oral non-absorbable antibiotic
• Cefazolin
Intravenous antibiotic to be given on anesthesia induction and prior to incision as a prophylactic antibiotic.
• Metronidazole
Intravenous antibiotic to be given on anesthesia induction and prior to incision as prophylactic antibiotic.

Other:
• Nil per os
Fasting orders according to anesthesia prior to surgery: No solid for >=8 hours, no formula milk/full liquids >= 4hours; no breast milk or clear fluids >=2hours.
• Clear fluids the day before surgery
As part of bowel preparation, participants will be asked to stick to clear fluids following breakfast the day before surgery. Breast milk is allowed if applicable.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	McMaster Pediatric Surgery Rresearch Collaborative (MPSRC)

References & Publications (15)

Ares GJ, Helenowski I, Hunter CJ, Madonna M, Reynolds M, Lautz T. Effect of preadmission bowel preparation on outcomes of elective colorectal procedures in young children. J Pediatr Surg. 2018 Apr;53(4):704-707. doi: 10.1016/j.jpedsurg.2017.03.060. Epub 2017 Mar 30. — View Citation

Billingham SA, Whitehead AL, Julious SA. An audit of sample sizes for pilot and feasibility trials being undertaken in the United Kingdom registered in the United Kingdom Clinical Research Network database. BMC Med Res Methodol. 2013 Aug 20;13:104. doi: 10.1186/1471-2288-13-104. — View Citation

Breckler FD, Rescorla FJ, Billmire DF. Wound infection after colostomy closure for imperforate anus in children: utility of preoperative oral antibiotics. J Pediatr Surg. 2010 Jul;45(7):1509-13. doi: 10.1016/j.jpedsurg.2009.10.054. Erratum in: J Pediatr Surg. 2010 Nov;45(11):2292. — View Citation

Güenaga KF, Matos D, Wille-Jørgensen P. Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD001544. doi: 10.1002/14651858.CD001544.pub4. Review. — View Citation

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. — View Citation

Janssen Lok M, Miyake H, O'Connell JS, Seo S, Pierro A. The value of mechanical bowel preparation prior to pediatric colorectal surgery: a systematic review and meta-analysis. Pediatr Surg Int. 2018 Dec;34(12):1305-1320. doi: 10.1007/s00383-018-4345-y. Epub 2018 Oct 20. — View Citation

Julious, S. A. (2005). Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics, 4, 287-291.

Koullouros M, Khan N, Aly EH. The role of oral antibiotics prophylaxis in prevention of surgical site infection in colorectal surgery. Int J Colorectal Dis. 2017 Jan;32(1):1-18. doi: 10.1007/s00384-016-2662-y. Epub 2016 Oct 24. Review. — View Citation

Nelson RL, Gladman E, Barbateskovic M. Antimicrobial prophylaxis for colorectal surgery. Cochrane Database Syst Rev. 2014 May 9;(5):CD001181. doi: 10.1002/14651858.CD001181.pub4. Review. — View Citation

Nelson RM, Ross LF. In defense of a single standard of research risk for all children. J Pediatr. 2005 Nov;147(5):565-6. — View Citation

Rangel SJ, Islam S, St Peter SD, Goldin AB, Abdullah F, Downard CD, Saito JM, Blakely ML, Puligandla PS, Dasgupta R, Austin M, Chen LE, Renaud E, Arca MJ, Calkins CM. Prevention of infectious complications after elective colorectal surgery in children: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee comprehensive review. J Pediatr Surg. 2015 Jan;50(1):192-200. doi: 10.1016/j.jpedsurg.2014.11.028. Epub 2014 Nov 12. Review. — View Citation

Serrurier K, Liu J, Breckler F, Khozeimeh N, Billmire D, Gingalewski C, Gollin G. A multicenter evaluation of the role of mechanical bowel preparation in pediatric colostomy takedown. J Pediatr Surg. 2012 Jan;47(1):190-3. doi: 10.1016/j.jpedsurg.2011.10.044. — View Citation

Smith RL, Bohl JK, McElearney ST, Friel CM, Barclay MM, Sawyer RG, Foley EF. Wound infection after elective colorectal resection. Ann Surg. 2004 May;239(5):599-605; discussion 605-7. — View Citation

Toh JWT, Phan K, Hitos K, Pathma-Nathan N, El-Khoury T, Richardson AJ, Morgan G, Engel A, Ctercteko G. Association of Mechanical Bowel Preparation and Oral Antibiotics Before Elective Colorectal Surgery With Surgical Site Infection: A Network Meta-analysis. JAMA Netw Open. 2018 Oct 5;1(6):e183226. doi: 10.1001/jamanetworkopen.2018.3226. — View Citation

Zwart K, Van Ginkel DJ, Hulsker CCC, Witvliet MJ, Van Herwaarden-Lindeboom MYA. Does Mechanical Bowel Preparation Reduce the Risk of Developing Infectious Complications in Pediatric Colorectal Surgery? A Systematic Review and Meta-Analysis. J Pediatr. 2018 Dec;203:288-293.e1. doi: 10.1016/j.jpeds.2018.07.057. Epub 2018 Sep 12. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility (no. enrolled)	recruitment rate (percentage of eligible patients enrolled and retained to the end of study).	From randomization to 30 days post-operatively
Primary	rate of post-randomization exclusions	Patients excluded after being randomized	From randomization to 30 days post-operatively
Primary	Protocol deviations	Number of protocol deviations	From randomization to 30 days post-operatively
Primary	Adverse events	Any expected and unexpected adverse event, with grade of adverse event	From randomization to 30 days post-operatively
Primary	Incomplete follow-up	Number missing follow-up appointments at 2 week mark	From randomization to 30 days post-operatively
Secondary	Superficial Incisional surgical site infection (SSI)	Rate of SI-SSI (superficial or deep, number of patients who developed SSI per group/subgroup).	30 days post-operatively.
Secondary	Deep incisional surgical site infection (SSI)	Rate of DI-SSI (number of patients who developed SSI per group/subgroup).	30 days post-operatively.
Secondary	Organ space - Surgical site infection (SSI)	Rate of OS- SSI (number of patients who developed OS-SSI per group/subgroup).	30 days post-operatively.
Secondary	Anastomotic leak - Surgical site infection (SSI)	Rate of anastomotic leak (verified by a contrast study or intra-operatively) (number of patients who developed OS-SSI per group/subgroup).	30 days post-operatively.
Secondary	Length of hospital stay	Post-operative hospitalization on primary admission in days	30 days post-operatively.
Secondary	Time to full enteric feed.	Post-operative return to full feed/diet in days	30 days post-operatively.
Secondary	Re-admission	admission in post-operative period for a reason related to the surgery (yes/No)	30 days post-operatively.
Secondary	Re-operation	Yes/No. Note:operation indication is directly related to the surgery	30 days post-operatively.
Secondary	Electrolyte disturbance	significant changes in electrolytes (abnormal levels) (Yes/No)	On day of surgery
Secondary	Electrolyte disturbance	If abnormal levels were detected, whether this was associate by clinical signs (Yes/No)	On day of surgery
Secondary	Clostridium difficile infection	Occurrence of C. difficile infection post-operatively (Yes/No)	30 days post-operatively.