Perioperative SDD to Prevent Infectious Complications After Esophagectomy

Official title

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)

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

Detailed description

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.

Interventions

• Drug SDD
  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 surger

Primary outcome measures

• the cumulative incidence of postoperative pneumonia within 30 days after surgery [Time frame: Within 30 days after surgery]

Secondary outcome measures (10)

• the cumulative incidence of all postoperative infectious complications within 30 days after surgery [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 [Time frame: Within 30 days after surgery]
• the mortality rate within 90 days after surgery [Time frame: Within 90 days after surgery]
• the rate of re-operation within 30 days after surgery [Time frame: Within 30 days after surgery]
• the postoperative length of stay on the intensive care unit (ICU) within 6 months after surgery defined in days [Time frame: Within 6 months after surgery]
• the postoperative length of the total hospital stay within 6 months after surgery defined in days [Time frame: Within 6 months after surgery]
• Quality of life questionnaire (EORTC QLQ C30) [Time frame: After 30 days, 3 months and 6 months after surgery]
• Quality of life questionnaire (EORTC QLQ OG25) [Time frame: After 30 days, 3 months and 6 months after surgery]
• Quality of life questionnaire (EQ-5D-5L) [Time frame: After 30 days, 3 months and 6 months after surgery]
• Direct and indirect costs defined in Euros [Time frame: Up to 6 months after surgery]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Belgium · 1 center

• UZ Leuven — Leuven

Netherlands · 1 center

• Radboudumc — Nijmegen

Publications

• Low DE, Alderson D, Cecconello I, Chang AC, Darling GE, D'Journo XB, Griffin SM, Holscher AH, Hofstetter WL, Jobe BA, Kitagawa Y, Kucharczuk JC, Law SY, Lerut TE, Maynard N, Pera M, Peters JH, Pramesh CS, Reynolds JV, Smithers BM, van Lanschot JJ. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Gro PMID 25607756
• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, PMID 34599691
• Grootenhuis JGA, Seurs W, Garms LM, de Vries M, Ubels S, van Werkhoven HC, Rosman C, Schouten JA, Klarenbeek BR, Van Veer H. 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. T PMID 41345690

Identifiers

NCT: NCT05865743 · 2023-504144-33-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗