Perioperative SDD to Prevent Infectious Complications After Esophagectomy

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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PERi-operative Selective Decontamination of the Digestive Tract to Prevent Severe Infectious Complications After Esophagectomy: a Randomized Multicenter Clinical Trial in Patients With Primary Resectable Esophageal Carcinoma (cT1-4, N0-3, M0)

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: SDD


Participation Criteria
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Eligibility Criteria
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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 undergoing CVVH. Patients with the inability to swallow the SDD

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SDD treatment<br>Standard of care + SDD (an antibiotic drink of 10ml suspension containing amphotericin B (50 mg/ml), colistin sulphate (10 mg/ml), and tobramycin (8 mg/ml) | Drug: SDD<br>* a 10ml suspension containing amphotericin B (50 mg/ml), colistin sulphate (10 mg/ml), and tobramycin (8 mg/ml). Patients take the oral 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<br>* Other names: Standard of care;|
| No Intervention: Standard of care<br>Standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Within 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the cumulative incidence of all postoperative infectious complications as registered in DUCA within 30 days after surgery | the cumulative incidence of all postoperative infectious complications as registered in DUCA (postoperative pneumonia, Clostridium difficile infection, 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), other infections requiring antibiotics. All these complications are then graded according to the Clavien-Dindo classification | 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 | Within 30 days after surgery | 
| the mortality rate within 90 days after surgery | All-cause mortality | Within 90 days after surgery | 
| the rate of re-operation within 30 days after surgery | Rate of re-operation | Within 30 days after surgery | 
| the postoperative length of stay on the intensive care unit (ICU) within 6 months after surgery defined in days | the postoperative length of stay on the intensive care unit (ICU), including re-admissions | Within 6 months after surgery | 
| the postoperative length of the total hospital stay within 6 months after surgery defined in days | the postoperative length of the total hospital stay, including re-admissions for any reasons within 6 months after surgery | Within 6 months after surgery | 
| Quality of life questionnaire (EORTC QLQ C30) | This study aims to determine the differences in the quality of life after 30 days, 3 months and 6 months after surgery using the following questionnaire European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ C30): All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Using paper or electronical forms, whatever a participant prefers paper forms or a printed version will be provided. | After 30 days, 3 months and 6 months after surgery | 
| Quality of life questionnaire (EORTC QLQ OG25) | This study aims to determine the differences in the quality of life after 30 days, 3 months and 6 months after surgery using the following questionnaire European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Oesophago Gastric module 25 (EORTC QLQ OG25): All of the scales and single-item measures range in score from 0 to 100. A high score for all the scales and single-items represents a high level of symptomatology or problems. Using paper or electronical forms, whatever a participant prefers paper forms or a printed version will be provided. | After 30 days, 3 months and 6 months after surgery | 
| Quality of life questionnaire (EQ-5D-5L) | •This study aims to determine the differences in the quality of life after 30 days, 3 months and 6 months after surgery using the following questionnaire The 5-level EuroQol-5D-5L (EQ-5D-5L). This descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. It is scaled from 0 to 100%. A higher score indicates a higher quality of life. Using paper or electronical forms, whatever a participant prefers paper forms or a printed version will be provided. | After 30 days, 3 months and 6 months after surgery | 
| Direct and indirect costs defined in Euros | The in-hospital and societal costs up to 6 months after surgery will be estimated with the help of the medical consumption questionnaire and the productivity cost questionnaire, developed by the iMTA. For Belgium a database cross linkage with the RIZIV/INAMI expenses is foreseen based on data pseudonymized by a Trusted Third Party and handled by KCE. The Belgian national patient identifier number will be used for data linkage with the expenses database of the health insurance provider, but will be withdrawn from the dataset by KCE before the analysis is performed. | Up to 6 months after surgery |