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

Bladder Cancer Clinical Trial

— INCyst  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05726786
• Other study ID #: INCyst
• Status: Recruiting
• Phase: Phase 3
• Start date: April 10, 2023
• Est. completion date: October 2026

Study information

• Verified date: September 2023
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: Ilaria Lucca, MD
• Phone: +41213142981
• Email: ilaria.lucca[@]chuv.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 232
• Est. completion date: October 2026
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bladder Cancer
• Bladder Disease
• Cystitis
• Cystitis, Interstitial
• Endometriosis
• Hemorrhagic Cystitis
• Interstitial Cystitis
• Neurogenic Bladder
• Painful Bladder Syndrome
• Urinary Bladder Diseases
• Urinary Bladder, Neurogenic

Intervention

Drug:
• Immunonutrition
Immunonutrition: Oral Impact®, Nestle´ 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

Locations

Country	Name	City	State
Switzerland	University Hospital of Bern	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois, CHUV	Lausanne	VD
Switzerland	Hospital of Riviera-Chablais	Rennaz

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois	Hôpital Riviera-Chablais, Vaud-Valais, Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cancer-specific survival rate	Long term overall and cancer-specific survival for bladder cancer patients	Postoperative time
Other	Quality of life assessment	Assessment of the quality of life after surgery through a questionnaire (EORTC QLQ-C30)	30 and 90 days after surgery
Other	Identification of biomarkers predictive of postoperative complications	Identification of biomarkers predictive of postoperative complications studying the patient's immune and microbiome signature: analysis of immune cells in the blood, analysis of the polyfunctionality of blood T cells, analysis of immune-related proteins in the urine and serum, microbiota analysis, expression of Argininosuccinate synthetase 1	Before and after immunonutrition treatement
Primary	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	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
Secondary	Mortality rate	Determination of the mortality rate at 30 and 90 days after surgery	30 and 90 days after surgery
Secondary	Complication-free survival rate	Determination of the post-operative complication-free survival	90-days after surgery
Secondary	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)