Bladder Cancer, Bladder Disease, Endometriosis, Hemorrhagic Cystitis, Interstitial Cystitis, Neurogenic Bladder, Painful Bladder Syndrome
Conditions
Keywords
Cystectomy, Immunonutrition, Complication, Malnutrition
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.
Interventions
DRUGImmunonutrition
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
Sponsors
Insel Gruppe AG, University Hospital Bern
Hôpital Riviera-Chablais, Vaud-Valais
University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Multicenter, prospective, controlled, pragmatic, parallel-group comparative study with block randomization stratified by centers
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Identification of biomarkers predictive of postoperative complications | Before and after immunonutrition treatement | 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 |
| Quality of life assessment | 30 and 90 days after surgery | Assessment of the quality of life after surgery through a questionnaire (EORTC QLQ-C30) |
| Cancer-specific survival rate | Postoperative time | Long term overall and cancer-specific survival for bladder cancer patients |
Countries
Switzerland
Contacts
Primary ContactIlaria Lucca, MD
Outcome results
None listed