Single- Versus Multiple-dose Antimicrobial Prophylaxis for The Prevention of Infectious Complications Associated With Peroral Endoscopic Myotomy(POEM) for Achalasia

Single- Versus Multiple-dose Antimicrobial Prophylaxis for The Prevention of Infectious Complications Associated With Peroral Endoscopic Myotomy(POEM) for Achalasia: A Triple-Blind, Randomized Controlled, Non-Inferiority Trial

Peroral endoscopic myotomy is a novel, promising endoscopic technique for achalasia considering its minimal invasive characteristics and comparable efficacy to Heller myotomy. Numerous studies have focused on the efficacy, safety as well as technical aspects of POEM. However, few efforts have been made to the issue of antimicrobial prophylaxis in POEM. Postoperative prophylactic antibiotics are universally initiated on call to the operating room or at the start of POEM and consist of second-generation cephalosporins. The mean duration of antibiotic regimen after POEM was 3 days ranging from 1 day to 7 days.

Numerous studies have shown that a single dose of antibiotic prophylaxis in a variety of surgical procedures. Other studies have shown that prolonged administration of antibiotics for longer than 24 hours add no benefit in many surgeries. Prolonged use of antibiotics not only increases the costs and exposure to drug toxicity directly but also may be associated with an increased risk of acquired antibiotic resistance as well as infection with Clostridium difficile.

Thus, investigators intend to perform a prospective randomized study to confirm the validity of single-dose antimicrobial prophylaxis for the prevention of infectious complications following peroral endoscopic myotomy.

Study Overview

• Status: Unknown
• Conditions: Esophageal Achalasia
• Intervention / Treatment: Drug: Saline Solution; Drug: Ceftazidime

Detailed Description

This prospective randomized trial is performed to confirm the noninferiority of single-dose versus multiple-dose antimicrobial prophylaxis in terms of the incidence of infectious complications associated with peroral endoscopic myotomy. Six hundred sixty-six patients undergoing POEM for achalasia will be randomized to receive only single-dose ceftazidime (2g) or an additional 2 doses every 12 hours postoperatively (multi-dose group). POEM associated infectious complications will be assessed and recorded as regional infections, remote infections and systemic infections. Infection rate, adverse events related to antibiotics and POEM, Clavien-Dindo classification of surgical complications, length of hospital stay and efficacy of POEM will be compared. Body fluid bacterial culture will be conducted in patients suspected of infectious complications.

• Study Type: Interventional
• Enrollment (Anticipated): 666
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed of esophageal achalasia
• Patients or legal surrogates willing and competent to give informed consent and to comply with follow up visits and tests

Exclusion Criteria:

• Patients with ASA score ≥3
• Patients with indications for antibiotic prophylaxis(infective endocarditis or other conditions) as determined by the American Society for Gastrointestinal Endoscopy
• Patients who have received antibiotics in the past seven days
• Patients who have possible signs of infection during preparation for POEM
• Pregnant
• Immunodeficient patients such as severe neutropenia(<0.5x1068/l) and/or advanced hematological malignancy
• Under steroid therapy
• Patients who develop intraoperative severe adverse events including severe choking and aspiration during endotracheal intubation requiring antibiotic treatment as well as severe pneumothorax, perforation, bleeding and mucosal injury cannot be closed by clips.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-dose group; Ceftazidime 2g at the start of POEM	Drug: Saline Solution; These patients will be given only one dose of ceftazidime at the start of POEM plus 2 doses of saline solution every 12 hours after the procedure.
Active Comparator: Multiple-dose group; Ceftazidime 2g at the start of POEM plus additional 2 doses given every 12 hours after the procedure	Drug: Ceftazidime; These patients will be given ceftazidime 2g at the start of POEM plus additional 2 doses given every 12 hours after the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infectious complications associated with POEM	Including regional, remote and systemic infections.	From operation day to 4 weeks after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathogens for causing infection	Body fluid will be collected and cultured in patients suspected of infectious complications	From operation day to 4 weeks after the procedure
Adverse effects of antibiotics	Any adverse events related to ceftazidime will be recorded.	From operation day to 4 weeks after the procedure
Clavien-Dindo classification of surgical complications	Clavien-Dindo classification of surgical complications is recorded if adverse events happen related to POEM	From operation day to 4 weeks after the procedure
Length of hospital stay	Length of hospital stay will be extracted.	From admission to discharge
Efficacy of POEM	Eckardt score will be compared before and after POEM.Clinical scoring system for achalasia (Eckardt score) Score Symptom Weight loss (kg)(0-3), Dysphagia(0-3), Retrosternal pain(0-3), Regurgitation(0-3)	admission to 4 weeks after POEM

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Study Chair: Ping-Hong Zhou, MD, PhD, Zhongshan Hospital, Fudan University, Shanghai, China

Publications and helpful links

General Publications

• Stavropoulos SN, Modayil RJ, Friedel D, Savides T. The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM experience. Surg Endosc. 2013 Sep;27(9):3322-38. doi: 10.1007/s00464-013-2913-8. Epub 2013 Apr 3.
• Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, Satodate H, Odaka N, Itoh H, Kudo S. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010 Apr;42(4):265-71. doi: 10.1055/s-0029-1244080. Epub 2010 Mar 30.
• Imamura H, Kurokawa Y, Tsujinaka T, Inoue K, Kimura Y, Iijima S, Shimokawa T, Furukawa H. Intraoperative versus extended antimicrobial prophylaxis after gastric cancer surgery: a phase 3, open-label, randomised controlled, non-inferiority trial. Lancet Infect Dis. 2012 May;12(5):381-7. doi: 10.1016/S1473-3099(11)70370-X. Epub 2012 Jan 31.
• ASGE Standards of Practice Committee, Khashab MA, Chithadi KV, Acosta RD, Bruining DH, Chandrasekhara V, Eloubeidi MA, Fanelli RD, Faulx AL, Fonkalsrud L, Lightdale JR, Muthusamy VR, Pasha SF, Saltzman JR, Shaukat A, Wang A, Cash BD. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc. 2015 Jan;81(1):81-9. doi: 10.1016/j.gie.2014.08.008. Epub 2014 Nov 11. No abstract available.
• Mohri Y, Tonouchi H, Kobayashi M, Nakai K, Kusunoki M; Mie Surgical Infection Research Group. Randomized clinical trial of single- versus multiple-dose antimicrobial prophylaxis in gastric cancer surgery. Br J Surg. 2007 Jun;94(6):683-8. doi: 10.1002/bjs.5837.
• Zhang XC, Li QL, Xu MD, Chen SY, Zhong YS, Zhang YQ, Chen WF, Ma LL, Qin WZ, Hu JW, Cai MY, Yao LQ, Zhou PH. Major perioperative adverse events of peroral endoscopic myotomy: a systematic 5-year analysis. Endoscopy. 2016 Nov;48(11):967-978. doi: 10.1055/s-0042-110397. Epub 2016 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 13, 2018
• First Posted (Actual): January 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 7, 2018
• Last Update Submitted That Met QC Criteria: November 6, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Antibiotic prophylaxis; Infectious complications; Peroral endoscopic myotomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Infections; Communicable Diseases; Esophageal Achalasia; Anti-Infective Agents; Anti-Bacterial Agents; Ceftazidime
• Other Study ID Numbers: ABX for POEM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No