Clinical trial NCT03404739: Single- Versus Multiple-dose Antimicrobial Prophylaxis for The Prevention of Infectious Complications Associated With Peroral Endoscopic Myotomy(POEM) for Achalasia
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Esophageal Achalasia
Keywords: Antibiotic prophylaxis
Infectious complications
Peroral endoscopic myotomy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2018-01-19
Enrollment: 666
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single- versus multiple-dose antimicrobial prophylaxis
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Infectious complications associated with POEM
timeFrame: From operation day to 4 weeks after the procedure
Secondary outcomes:
measure: Pathogens for causing infection
timeFrame: From operation day to 4 weeks after the procedure
measure: Adverse effects of antibiotics
timeFrame: From operation day to 4 weeks after the procedure
measure: Clavien-Dindo classification of surgical complications
timeFrame: From operation day to 4 weeks after the procedure
measure: Length of hospital stay
timeFrame: From admission to discharge
measure: Efficacy of POEM
timeFrame: admission to 4 weeks after POEM
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Zhongshan Hospital, Fudan University, Shanghai, China
name: Ping-Hong Zhou, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.