PERi-operative Selective Decontamination of the digestive tract to prevent severe infectious complications after Esophageal Resection: study protocol of the PERSuaDER-trial, a multicenter randomized controlled trial in patients with primary resectable esophageal carcinoma

Abstract

Background: Esophagectomy is a highly complex surgical procedure, and it is associated with significant morbidity and mortality. The postoperative complication rate is high, with pneumonia being the most common. These are thought to arise from (micro-)aspiration of bacteria residing in the oropharyngeal and gastrointestinal (GI) tract. Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic strategy aimed at preventing these infections. SDD decolonizes the oropharyngeal and GI tract from pathogenic aerobic gram-negative rods, fungi and yeasts, while anaerobic, protective microbiota are preserved. The PERSuaDER trial aims to evaluate whether perioperative SDD can reduce postoperative pneumonia after esophagectomy. Methods: The PERSuaDER-trial is a randomized, controlled, open-label, superiority, multicenter, pragmatic, group-sequential trial aiming to include 854 patients with primary resectable esophageal carcinoma ((y)cT1-4a N0-3 M0) scheduled for transthoracic esophagectomy. The intervention group will receive SDD prophylaxis in addition to the standard care regimen. The SDD treatment comprises two oral liquids: an oral suspension containing amphotericin B and an oral solution containing both colistin sulfate and tobramycin. Participants are required to swallow the SDD suspension four times a day for 1 week, starting 3 days prior to the surgical procedure, with two doses on the day of surgery. All other aspects of care are identical to those provided to the control group (standard care without SDD). Participants will be asked to keep a diary and fill out quality of life, medical consumption, and productivity cost questionnaires. Interim analyses will take place after 30% and 60% of the participants have completed follow-up of 30 days after surgery, and after completion or termination of the trial. Discussion: It is hypothesized that the addition of SDD to the standard peri-operative care in esophageal cancer surgery will result in a reduction in the incidence of postoperative pneumonia. Furthermore, the trial will evaluate the impact of SDD on postoperative (infectious) complications and quality of life, and its cost-effectiveness. Trial registration: The PERSuaDER trial is registered in ClinicalTrials.gov (NCT05865743) and the European Clinical Trials Information System (CTIS) (EU Trial number: 2023-504144-33), Trial authorization date: 25.03.2024, protocol version 1.1, date: 03.03.2024.