Pre-operative Immuno-Nutrition in Radical Cystectomy

Official title

Pre-operative Immuno-nutrition in Patients Undergoing Radical Cystectomy for Bladder Cancer: a Multicentre, Randomised, Open-label, Parallel Group Study

Overview

This study will evaluate the effect of preoperative oral immunonutrition on postoperative complications in patients undergoing radical cystectomy for bladder cancer. Patients receiving preoperative immunonutrition will be compared to controls receiving a standard high-calorie, high-protein oral nutritional supplement.

Detailed description

Radical cystectomy with pelvic lymph node dissection and urinary reconstruction is a major surgical procedure performed for bladder cancer. The literature reports an incidence of 50-88% and 30-42% for any grade complications (Clavier-Dindo grade I-IV) and severe complications (Clavier-Dindo grade ≥III), respectively. Nutritional status prior to radical cystectomy has been shown to be a strong predictor of 90-day mortality. The term "immunonutrition" refers to the oral or enteral administration of specific substrates such as omega-3 fatty acids, arginine, and nucleotides. These substrates have been shown to upregulate the host immune response, modulate inflammatory responses and improve protein synthesis after surgery, with a favorable impact on postoperative infection rates and length of hospital stay in major abdominal surgery. Data on patients undergoing radical cystectomy are scarce, mainly due to the small sample size of the studies. However, the available evidence suggests a potential beneficial effect of this nutritional intervention in patients undergoing radical cystectomy. Several aspects remain largely unclear, including the dosage and timing of immunonutrition and the impact of preoperative malnutrition risk on the efficacy of immunonutrition. This study will evaluate the effect of 7 days of preoperative immunonutrition on postoperative complications compared to patients receiving standard high-calorie, high-protein oral nutritional supplements.

Interventions

• Dietary supplement Immunonutrition
  This formula is enriched in arginine, nucleotides (RNA) and omega-3 fatty acids and provides, with the proposed therapeutic volume (2 units per day), 36 grams of protein and 682 kcal/day.
• Dietary supplement Standard Oral Nutritional Supplement
  This formula provides 38 grams of protein and 500 kcal/day with the proposed therapeutic volume.

Primary outcome measures

• 30-day complications [Time frame: 30 days after surgery]

Secondary outcome measures (12)

• 30-day severe complications [Time frame: 30 days after surgery]
• 90-day severe complications [Time frame: 90 days after surgery]
• 30-day and 90-day infectious complications [Time frame: 30 and 90 days after surgery]
• 30-day and 90-day occurrence of other medical conditions [Time frame: 30 and 90 days after surgery]
• Time to recovery of bowel function [Time frame: Immediately after surgery]
• Time to postoperative mobilization [Time frame: Immediately after surgery]
• Muscular strength modifications [Time frame: Up hospital discharge, assessed up to 90 days]
• Weight modifications [Time frame: From preadmission visit to 90-day follow-up visit]
• Biochemical nutritional indexes modifications [Time frame: Up to hospital discharge, assessed up to 90 days]
• Need of blood transfusions [Time frame: Immediately after surgery]
• Length of stay [Time frame: Immediately after surgery]
• Readmission rate [Time frame: 30 and 90 days after surgery]

Eligibility criteria

Inclusion criteria

• Surgical indication to radical cystectomy with diagnosis of muscle invasive bladder cancer (any N, any M), BCG (Bacillus Calmette-Guerin)-unresponsive non-muscle invasive bladder cancer or extensive non-muscle invasive bladder cancer that cannot be treated with endoscopic surgery alone;
• Willingness to participate by signing written informed consent.

Exclusion criteria

• Age < 18 years;
• Pregnant or lactating women;
• Participation in another study with nutritional supplements within the 30 days preceding and during the present study
• Known hypersensitivity or allergy to components of immunonutrition or standard high-calorie high-protein oral nutritional supplement;
• Need for artificial nutrition support due to totally compromised spontaneous food intake;
• Diarrhoea with suspected malabsorption syndrome;
• Inability to consume oral supplements as a consequence of pre-existing disease (e.g. dysphagia) or other factors (e.g. language barrier, psychological disorders, absence of a home caregiver in dependent or elderly patients);
• Kidney failure with need for renal replacement therapy;
• Type 1 diabetes mellitus;
• Type 2 diabetes mellitus requiring insulin therapy and/or inadequate glycaemic control (glycosylated haemoglobin ≥7% and/or fasting plasma glucose ≥150 mg/dL);
• Inability to give an informed consent.

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

Single blind

Primary purpose

Treatment

Study locations

Italy · 2 centers

• IRCCS Ospedale San Raffaele — Milan
• Fondazione IRCCS Policlinico San Matteo — Pavia

Publications

• Casirati A, Da Prat V, Bettiga A, Aretano L, Trevisani F, Cereda E, Briganti A, Colombo E, Preziati G, De Simeis F, Salonia A, Montorsi F, Caccialanza R, Naspro R. Immunonutrition in Radical Cystectomy: State of the Art and Perspectives. Cancers (Basel). 2023 Jul 24;15(14):3747. doi: 10.3390/cancers15143747. PMID 37509408

Identifiers

NCT: NCT06355518 · INu-RC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗