Pre-operative Immuno-Nutrition in Radical Cystectomy (INu-RC)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Dietary supplement: Immunonutrition; Dietary supplement: Standard 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.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Riccardo Caccialanza, MD; Phone Number: +390382501615; Email: r.caccialanza@smatteo.pv.it
• Study Contact Backup: Name: Valentina Da Prat, MD; Phone Number: +390382501615; Email: v.daprat@smatteo.pv.it

Study Locations

• Italy
  • Milan, Italy, 20132
    • Irccs Ospedale San Raffaele
    • Contact: Bettiga Arianna; Email: bettiga.arianna@hsr.it
    • Principal Investigator: Marco Moschini, MD
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Ferrari Alessandra, PharmD; Phone Number: +390382503689; Email: alessandra.ferrari@smatteo.pv.it
    • Principal Investigator: Valentina Da Prat, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative Immunonutrition; Preoperative administration of a high-calorie, high-protein liquid oral nutritional supplement containing immunonutrients [Impact® Oral (237 mL per serving); Nestlé Health Science - Creully Sur Seulles - France]. Two units of Impact® Oral per day will be administered for 7 days before surgery.	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.; Other Names: Impact® Oral
Active Comparator: Preoperative Standard Oral Nutritional Supplement; Preoperative administration of a standard high-calorie-high-protein liquid oral nutritional supplement [Meritene® Protein Drink (200 mL per serving); Nestlé Health Science - Creully Sur Seulles - France]. Two units of Meritene® Protein Drink per day will be administered for 7 days before surgery.	Dietary supplement: Standard Oral Nutritional Supplement; This formula provides 38 grams of protein and 500 kcal/day with the proposed therapeutic volume.; Other Names: Meritene® Drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day complications	Percentage of patients developing at least one post-operative complication (as detailed in the study protocol: infectious, urinary, gastrointestinal, and wound-related complications)	30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day severe complications	Percentage of patients developing at least one Clavien-Dindo grade ≥III post-operative complication (as detailed in the study protocol: infectious, urinary, gastrointestinal, and wound-related complications)	30 days after surgery
90-day severe complications	Percentage of patients developing at least one Clavien-Dindo grade ≥III post-operative complication (as detailed in the study protocol: infectious, urinary, gastrointestinal, and wound-related complications)	90 days after surgery
30-day and 90-day infectious complications	Percentage of patients developing at least one infectious complication (as detailed in the study protocol)	30 and 90 days after surgery
30-day and 90-day occurrence of other medical conditions	Percentage of patients developing at least one other medical conditions (as detailed in the study protocol)	30 and 90 days after surgery
Time to recovery of bowel function	Time from surgery to first flatus counting the day of surgery as day 0	Immediately after surgery
Time to postoperative mobilization	Time from surgery to first walk counting the day of surgery as day 0	Immediately after surgery
Muscular strength modifications	Difference in hand-grip strength (mean of three consecutive measurements from dominant hand) and in the sit-and-stand test	Up hospital discharge, assessed up to 90 days
Weight modifications	Difference in body weight	From preadmission visit to 90-day follow-up visit
Biochemical nutritional indexes modifications	Biochemical nutritional indexes	Up to hospital discharge, assessed up to 90 days
Need of blood transfusions	Percentage of patients undergoing blood transfusions (red blood cells, plasma, and/or platelets)	Immediately after surgery
Length of stay	Time from hospital admission to discharge at home or to another facility	Immediately after surgery
Readmission rate	Incidence of unplanned re-hospitalization due to all causes	30 and 90 days after surgery
30-day and 90-day mortality	Death rate due to all causes	30 and 90 days after surgery
Compliance	Percentage of patients consuming ≥80% of the prescribed supplement	7 days before surgery
Tolerability (gastrointestinal symptoms related to nutritional supplement)	Percentage of patients experiencing at least one moderate-severe adverse gastrointestinal effects	7 days before surgery

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
• Collaborators: IRCCS Ospedale San Raffaele

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 4, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: INu-RC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No