Clinical trial NCT05865743: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Cancer
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Universitaire Ziekenhuizen KU Leuven
First posted: 2023-05-19
Enrollment: 854
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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).

Primary outcomes:
measure: the cumulative incidence of postoperative pneumonia within 30 days after surgery
timeFrame: Within 30 days after surgery
Secondary outcomes:
measure: the cumulative incidence of all postoperative infectious complications within 30 days after surgery
timeFrame: Within 30 days after surgery
measure: the cumulative incidence of anastomotic leakage within 30 days after esophagectomy for which endoscopic, radiologic, or surgical re-intervention is needed
timeFrame: Within 30 days after surgery
measure: the mortality rate within 90 days after surgery
timeFrame: Within 90 days after surgery
measure: the rate of re-operation within 30 days after surgery
timeFrame: Within 30 days after surgery
measure: the postoperative length of stay on the intensive care unit (ICU) within 6 months after surgery defined in days
timeFrame: Within 6 months after surgery
measure: the postoperative length of the total hospital stay within 6 months after surgery defined in days
timeFrame: Within 6 months after surgery
measure: Quality of life questionnaire (EORTC QLQ C30)
timeFrame: After 30 days, 3 months and 6 months after surgery
measure: Quality of life questionnaire (EORTC QLQ OG25)
timeFrame: After 30 days, 3 months and 6 months after surgery
measure: Quality of life questionnaire (EQ-5D-5L)
timeFrame: After 30 days, 3 months and 6 months after surgery
measure: Direct and indirect costs defined in Euros
timeFrame: Up to 6 months after surgery
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
affiliation: RadoudUMC
name: Camiel Rosman, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Group (ECCG). Ann Surg. 2015 Aug;262(2):286-94. doi: 10.1097/SLA.0000000000001098.
citation: 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, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.