The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy (INCyst Trial)

Phase 3

Recruiting

• Conditions: Bladder Cancer; Interstitial Cystitis; Painful Bladder Syndrome; Neurogenic Bladder; Hemorrhagic Cystitis; Endometriosis; Bladder Disease
• Interventions: Drug: Immunonutrition

• Registration Number: NCT05726786
• Lead Sponsor: Centre Hospitalier Universitaire Vaudois

Brief Summary

The goal of this clinical trial research study is to evaluate the impact of preoperative oral immunonutrition (IN) on post-operative complications in patients undergoing a cystectomy.

As a secondary focus, this study will aim to develop a signature that would identify patients that would benefit the most from IN.

This is a multicentric (Swiss: N=3), prospective, controlled, pragmatic, parallel-group comparative study with block randomization stratified by centers.

Detailed Description

Despite standardized surgical technique and the development of new perioperative care protocols, cystectomy morbidity remains a serious challenge for urologists. Most common postoperative complications, such as infections, often lead to longer length of stay and worse survival. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. Immunonutrition (IN), containing arginine, ribonucleic acid and omega-3 polyunsaturated fatty acids, aims to improve the nutritional status, immunological function and clinical outcome of surgical patients. Meta-analyses have demonstrated that preoperative IN reduces complications and length of hospital stay after major bowel surgery. Evidence-based data on preoperative oral IN support for cystectomy patients are lacking, which does not allow this treatment to be widely accepted, recommended, or reimbursed by health insurances in most European countries. Uncertainties also remain about the exact mechanism by which IN modulates the host immune response.

Complication rates after cystectomy range from 40-75%. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. To date, and in the last 20 years, no single intervention has allowed for a significant reduction in morbidity after cystectomy, which remains one of the highest in surgery. The present adequately powered multicenter RCT has the potential of changing current practice by recommending preoperative IN before cystectomy in case of positive results. If the present RCT demonstrates a benefit in administrating IN prior to cystectomy, urological guidelines will be modified accordingly to this new evidence. IN will then be recommended before cystectomy for the patient's benefit. The investigators truly believe that the proposed study is of high clinical importance with potential impact on perioperative urology guidelines.

Study Timeline

• Study First Submitted: 2023-01-16
• Study First Submitted QC: 2023-02-03
• Study First Posted: 2023-02-14
• Study Start: 2023-04-10
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-01
• Last Update Posted: 2023-09-05
• Primary Completion: 2026-08
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 232

Inclusion Criteria

• Patient undergoing open cystectomy (for all reasons)
• Age ≥18 years
• Ability and willingness to provide informed consent documented by signature

Read More

Exclusion Criteria

• Contraindications to IN, e.g. known hypersensitivity or allergy to lactose, fish oil or soy lecithin
• Severe diarrhoea requiring medical attention
• Current treatment with any immunosuppressive drug
• In standard practice, pregnant or lactating women are systematically rejected by the surgeon for this surgical procedure. Furthermore, during the pre-surgical anaesthesia consultation, the eligibility of each patient for anaesthesia will be assessed according to the usual criteria and recommendations of the anaesthesia service of the CHUV
• Other clinically significant concomitant disease affecting immunity (e.g., severe renal failure, HIV, SLE, transplant recipient, ...)
• Inability to follow the procedures of the study, e.g. due psychological disorders, dementia, etc.
• Participation in another study with investigational drug within the 30 days preceding and during the present study
• Previous enrolment into the current study
• Use of IN independently of the study
• Enrolment of the investigator, his/her family members, employees and other dependent persons
• Emergency procedure (less than 7 days between screening and surgery)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immunonutrition	Immunonutrition	Seven days of preoperative oral supplementation with an immune-enhanced oral nutrition

Primary Outcome Measures

Name	Time	Method
Infectious complication after cystectomy	30-days afetr surgery	Determination of infectious complications rate at 30 days after surgery (pneumonia, urinary tract infection, surgical site infection, sepsis, shock).

Secondary Outcome Measures

Name	Time	Method
Mortality rate	30 and 90 days after surgery	Determination of the mortality rate at 30 and 90 days after surgery
Comprehensive Complication Index (CCI)	30 and 90 days after surgery	Determination of the Comprehensive Complication Index (CCI) at 30 and 90 days after surgery. The range is between 0 (no complication) to 100 (death).
Complication-free survival rate	90-days after surgery	Determination of the post-operative complication-free survival
Treatment compliance rate	Between Day -30 and Day -10 and at preoperative admission after intake of the allocated nutrition (Day -1)	Serum arginine levels will be assessed at enrolment (between Day -30 and Day -10) and at preoperative admission after intake of the allocated nutrition (Day -1) in all patients treated at Lausanne, CHUV.

Trial Locations

Locations (3)

Hospital of Riviera-Chablais; 🇨🇭 Rennaz, Switzerland

Centre Hospitalier Universitaire Vaudois, CHUV; 🇨🇭 Lausanne, VD, Switzerland

University Hospital of Bern; 🇨🇭 Bern, Switzerland