Perioperative SDD to Prevent Infectious Complications After Esophagectomy

Phase 3RecruitingNCT05865743

Radboud University Medical Center854 enrolled

Overview

The primary aim of the PERSuaDER-trial is to evaluate the effect of SDD on infectious complications after esophagectomy, focussed on the prevention of pneumonia

Esophagectomy is a complex surgical procedure, associated with significant morbidity and mortality rates. Most postoperative complications are caused by infections (10-30%). These are thought to arise from (micro-)aspiration of bacteria residing in the oropharyngeal and gastrointestinal (GI) tract, leading to (respiratory) infections. Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic strategy that aims to prevent postoperative infections. Pathogenic aerobic gram-negative rods and yeasts tract are reduced, while anaerobic, protective microbiota are preserved. SDD has been shown to lower the risk for respiratory infections in an intensive care setting. Establishing SDD as effective addition to the standard care of esophagectomy patients is expected to increase their chance of survival.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

854

Conditions

Esophageal Cancer

Interventions

SDDDRUG

The intervention group receives SDD treatment additional to standard care, comprising two distinct liquids for oral administration: first the 5 ml amphotericin B suspension (100 mg/ml) and subsequently the 5 ml "SDD base for suspension", containing both colistin sulphate (20 mg/ml) and tobramycin sulphate (16 mg/ml). Patients take the 5 ml amphotericin B, followed by the 5 ml "SDD base for suspension", four times daily for one week, starting three days prior to the surgery. On the day of surgery, intake is limited to an early morning and a late evening dose.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of primary esophageal adenocarcinoma or squamous cell carcinoma (cT1b-4a,N0-3,M0) in the mid or distal esophagus or at the level of the gastro-esophageal junction scheduled for undergoing transthoracic esophagectomy with curative intent or for esophageal reconstruction with a gastric or jejunal interposition * Age ≥ 18 years, * Able to give written informed consent. Exclusion Criteria: * Patients planned for rescue surgery, * Patients planned for colonic interposition, * Known or suspected pregnancy, * Patients who have undergone upper GI surgery within 30 days before randomization, * Unable to understand the study information, study instructions and give informed consent. * Patients enrolled in a trial that would interact with the intervention * Patients with a known allergy, sensitivity, or interaction to investigational medicinal product. * Patients with known/documented colonization of Enterobacteriaceae and or Pseudomonas Aeruginosa that are resistant to both tobramycin/gentamicin and to carbapenem antibiotics * Patients undergoing CVVH. * Patients with documented chronic renal failure (GFR \< 15 mls/min) or who are on chronic intermittent hemo- or peritoneal dialysis, * Women of childbearing potential at risk of pregnancy, not using adequate contraception, * Patients with the inability to swallow the SDD * Patients with pre-existing degenerative neuromuscular diseases like, but not limited to, myasthenia gravis or Parkinson disease).

Locations (2)

UZ Leuven

Leuven, Belgium

RECRUITING

Radboudumc

Nijmegen, Netherlands

RECRUITING

Outcomes

Primary Outcomes

the cumulative incidence of postoperative pneumonia within 30 days after surgery

The primary outcome parameter is the cumulative incidence of postoperative pneumonia within 30 days after surgery. Pneumonia will be defined by the following criteria: * Positive sputum culture OR * Presence of a new progressive radiographic infiltrate plus at least 2 of the following clinical features: * Fever \> 38.5°C * Leukocytosis (\>11.0) or leukopenia (\<4.0) * Purulent secretions

Time frame: Within 30 days after surgery

Secondary Outcomes

the cumulative incidence of all postoperative infectious complications within 30 days after surgery

the cumulative incidence of all postoperative infectious complications as registered in DUCA (postoperative pneumonia, urinary tract infection, wound infection/abscess requiring wound opening or antibiotic treatment, central line infection requiring line removal or antibiotic treatment, intra-thoracic/intra-abdominal abscess, generalised sepsis as defined by Evans, Rhodes (2), infections with Highly-resistant Enterobacteriaceae (HRE) and Clostridium difficile, other infections requiring antibiotics. All these complications are then graded according to the Clavien-Dindo classification

Time frame: Within 30 days after surgery

the cumulative incidence of anastomotic leakage within 30 days after esophagectomy for which endoscopic, radiologic, or surgical re-intervention is needed

the cumulative incidence of anastomotic leakage within 30 days after esophagectomy for which endoscopic, radiologic, or surgical re-intervention is needed. This corresponds to the definition of the ECCG of anastomotic leakage type II and III Low, Alderson (3). Anastomotic leakage is defined by contrast leakage on CT-scan with intravenous and oral contrast (swallow CT-scan) upon clinical suspicion, by endoscopy or by drainage of ingested materials into the chest tube (thoracic anastomoses) or ingested materials or saliva into cervical wound (cervical anastomosis) or signs of anastomotic leakage during re-intervention or autopsy

Time frame: Within 30 days after surgery

Central Contacts

Justin Grootenhuis, MD

CONTACT

+31655740313 justin.grootenhuis@radboudumc.nl

Research Coordinator

CONTACT

+31655740313 persuader.heel@radboudumc.nl

Data from ClinicalTrials.gov

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