PERSuaDER: Perioperative SDD to Prevent Infectious Complications After Esophagectomy
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SDD treatment 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
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
Other Names:
|
| No Intervention: Standard of care Standard of care |
Outcome Measures
Primary Outcome Measures
- the cumulative incidence of postoperative pneumonia within 30 days after surgery [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 according to the definition of the Esophagectomy Complications Consensus Group (ECCG)(1) 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
Secondary Outcome Measures
- the cumulative incidence of all postoperative infectious complications as registered in DUCA within 30 days after surgery [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
- the cumulative incidence of anastomotic leakage within 30 days after esophagectomy for which endoscopic, radiologic, or surgical re-intervention is needed [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. 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
- the mortality rate within 90 days after surgery [Within 90 days after surgery]
All-cause mortality
- the rate of re-operation within 30 days after surgery [Within 30 days after surgery]
Rate of re-operation
- the postoperative length of stay on the intensive care unit (ICU) within 6 months after surgery defined in days [Within 6 months after surgery]
the postoperative length of stay on the intensive care unit (ICU), including re-admissions
- the postoperative length of the total hospital stay within 6 months after surgery defined in days [Within 6 months after surgery]
the postoperative length of the total hospital stay, including re-admissions for any reasons within 6 months after surgery
- Quality of life questionnaire (EORTC QLQ C30) [After 30 days, 3 months and 6 months after surgery]
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.
- Quality of life questionnaire (EORTC QLQ OG25) [After 30 days, 3 months and 6 months after surgery]
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.
- Quality of life questionnaire (EQ-5D-5L) [After 30 days, 3 months and 6 months after surgery]
•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.
- Direct and indirect costs defined in Euros [Up to 6 months after surgery]
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.
Eligibility Criteria
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 undergoing CVVH.
-
Patients with the inability to swallow the SDD
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Radboud University Medical Center
- ZonMw: The Netherlands Organisation for Health Research and Development
- Universitaire Ziekenhuizen KU Leuven
Investigators
- Principal Investigator: Camiel Rosman, Prof, RadoudUMC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- 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.
- 2023-504144-33-00