Perioperative SDD to Prevent Infectious Complications After Esophagectomy

Esophageal Cancer Clinical Trial

— PERSuaDER  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05865743
• Other study ID #: 2023-504144-33-00
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Radboud University Medical Center
• Contact: Justin Grootenhuis, MD
• Phone: +31655740313
• Email: justin.grootenhuis[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 854
• Est. completion date: December 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Esophageal Cancer

Intervention

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 surgery, intake is limited to an early morning and a late evening dose.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University Medical Center	Universitaire Ziekenhuizen KU Leuven, ZonMw: The Netherlands Organisation for Health Research and Development

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	the cumulative incidence of all postoperative infectious complications within 30 days after surgery	the cumulative incidence of all postoperative infectious complications as registered in DUCA (postoperative pneumonia, 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), infections with Highly-resistant Enterobacteriaceae (HRE) and Clostridium difficile, other infections requiring antibiotics. All these complications are then graded according to the Clavien-Dindo classification	Within 30 days after surgery
Secondary	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
Secondary	the mortality rate within 90 days after surgery	All-cause mortality	Within 90 days after surgery
Secondary	the rate of re-operation within 30 days after surgery	Rate of re-operation	Within 30 days after surgery
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   DUCA Data