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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Esophageal Achalasia

Intervention / Treatment
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* Drug: Saline Solution
* Drug: Ceftazidime


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: single- versus multiple-dose antimicrobial prophylaxis
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotic prophylaxis, Infectious complications, Peroral endoscopic myotomy