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

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy - A Multicenter Randomized Controlled Trial (INCyst Trial)

Conditions
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Bladder Cancer, Interstitial Cystitis, Painful Bladder Syndrome, Neurogenic Bladder, Hemorrhagic Cystitis, Endometriosis, Bladder Disease

Intervention / Treatment
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* Drug: Immunonutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient undergoing open cystectomy (for all reasons) Age ≥18 years Ability and willingness to provide informed consent documented by signature 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, prospective, controlled, pragmatic, parallel-group comparative study with block randomization stratified by centers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunonutrition<br>Seven days of preoperative oral supplementation with an immune-enhanced oral nutrition | Drug: Immunonutrition<br>* Immunonutrition: Oral Impact®, Nestlé Health Science, Switzerland. IN will be administered as per manufacturer suggestion, i.e. three times a day during 7 days preoperatively. Oral Impact® is a powdered oral feed that provides 309 kcal/bag<br>|
| No Intervention: No immunonutrition (control)<br>Standard of care | |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comprehensive Complication Index (CCI) | Determination of the Comprehensive Complication Index (CCI) at 30 and 90 days after surgery. The range is between 0 (no complication) to 100 (death). | 30 and 90 days after surgery | 
| Mortality rate | Determination of the mortality rate at 30 and 90 days after surgery | 30 and 90 days after surgery | 
| Complication-free survival rate | Determination of the post-operative complication-free survival | 90-days after surgery | 
| Treatment compliance rate | 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. | Between Day -30 and Day -10 and at preoperative admission after intake of the allocated nutrition (Day -1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystectomy, Immunonutrition, Complication, Malnutrition