Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery. (Prehab_2)

Elective surgery is the most effective treatment option for colorectal cancer, however it has been recognized to be associated with high morbidity and mortality risks.

ERAS (Enhanced Recovery After Surgery) is a preoperative multimodality treatment package, which has been well investigated and proved to be effective in reducing early postoperative morbidity, mortality, length of hospital stay and hospital costs, as well. Still, a good proportion of patients are not suitable for ERAS program, mainly based on lack of compliance and the impaired physical function before surgery.

Trimodal Prehabilitation Program is a recently introduced preoperative preparation (training) program, which addresses improvement of physical, mental and nutritional status of the high risk elective surgery patients.

This study aims to investigate the benefit of all efforts of a 4-6-week preoperative preparation program (Prehabilitation) being added to an established ERAS protocol.

Additionally the effect of trimodal prehabilitation on gut microbiom diversity and its relation to clinical outcome will be analyzed.

Study Overview

• Status: Suspended
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Trimodal rehabilitation + ERAS; Procedure: ERAS + nutritional prehabilitation

Detailed Description

Aim:

Colorectal cancer patients with a planned resection are tested if a complex, trimodal rehabilitation program can hold functional and morbidity benefit for them.

In the prospective, randomized (2:1) study control patient group will be the well established and tested ERAS (enhanced recovery after surgery) Program.

Study protocol in details:

First visit: Outpatient Department of Surgery

On both arms:

• History taking (including family history and oncologic history);
• Physical examination

Operation indication, type of procedure and date of procedure agreed; Organizing further investigations, anesthesia; Operative risk assessment ("ACS - surgical risk calculator"); Study patient identifier Nr generated; Nurse-led ERAS/Prehab clinic: randomization

On both arms:

• Randomization (Prehabilitation Program / ERAS Program). 2:1
• Nurse led clinic assessment ("study nurse"):

.i. CaseReportForm (CRF) filled in.

.ii. Patient data (personal data, demographics, history) .iii. Anthropometrics (BMI, MUST, Body fat % measurement). .iv. Mental hygienic status assessment (smoking, alcohol consumption, anxiety, depression, sleeping disorders).

.v. Cardiovascular status (resting HR, RR). .vi. Operative risk assessment (CR-Possum score). .vii. Preoperative counseling (operation type, preparation, pain management, discharge plan).

.viii. Preoperative nutritional planning (education, nutrient prescription). .ix. Alcohol intake and smoking cessation - information given. .x. Stoma education started. . xi. Consent signed, patient workbook handed over. .xii. Respiratory test referral. xiii. Fecal sample collected and stored at -86 C.

Physiotherapy, first visit

Both on control and interventional arms:

• Respiratory function test recorded.
• Physical status tested (6MWD) on a treadmill.

Just on Prehabilitation arm:

• Respiratory training education.
• Respiratory trainer device usage educated.
• Daily activity (walking) planned.

Physiotherapy - second/third/fourth visit (weekly)

Just on Prehabilitation arm:

Previous week activity reviewed as to workbook. Physical assessment: 6MWD, FVC. Next week activity planned. Psychic preparation

Just on Prehabilitation arm:

• Once a week half an hour group relaxation training - regardless of the stage of prehabilitation program.

Admission to the Surgical Ward a day before surgery

Both on control and interventional arm:

• Preoperative assessment:

.i. Anthropometrics (BMI, body fat%). .ii. Cardiovascular stage (resting HR and RR), ECG. .iii. Respiratory function tests. .iv. Physical status (6MWD) .v. Mental status (Hospital Anxiety and Depression Scale (HADS)) assessment. vi. Fecal sample collected and stored at -86 C.

• Preoperative preparation (as to ERAS protocol).
• Postoperative care (ITU, pain management, mobilization, oral nutrition built up, drains early removal, complications recorded (Clavien-Dindo-classification)).
• Stoma education.

Dietary education. On discharge: Quality of Life (QoL) SF36 - (36-Item Short Form Survey from the RAND Medical Outcomes Study).

Postoperative follow up:

Both on control and interventional arms:

• Assessment (8th week post op.):

.i. Anthropometrics (BMI, Body fat %) .ii. Cardiovascular status (resting HR and RR). .iii. Respiratory function tests. .iv. Physical status (6MWD). .v. Fecal sample collected and stored at -86 C.

- Long-term follow-up: 12, 24, 36, 48 and 60 months post operative assessment: Behavioral changes (alcohol abstinence, smoking cessation) Daily physical activity routine assessment. SF36 quality of life assessment Oncological outcome: local recurrence rate, distant recurrence rate, disease free survival, overall survival.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Balazs Banky, Dr; Phone Number: +36208231642; Email: bankybalazs@gmail.com
• Study Contact Backup: Name: Andras Fulop, Dr; Phone Number: +36208258989; Email: fuli4321@gmail.com

Study Locations

• Hungary
  • Tatabánya, Hungary, 2800
    • Department of Surgery, St. Borbala Hospital
  • Tatabánya, Hungary, 2800
    • St. Borbala Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patient with histologically proven primary colorectal adenocarcinoma
• any stage of colorectal cancer
• elective operation
• curative intention
• informed consent signed by patient

Exclusion Criteria:

• emergency operation
• palliative operation
• non-colorectal, second malignancy
• pregnancy
• patient not giving consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trimodal prehabilitation + ERAS; Patients receiving a formal preoperative preparation on: Physical status (walking, respiratory training) Nutrition (nutritional supplements) Mental status (weekly groups led by clinical psychologist on anxiety and depression management). Each patient will be treated in an ERAS program preoperatively.	Procedure: Trimodal rehabilitation + ERAS; Prehabilitation will cover a range preoperative education and exercises (weekly) on diet, physical activity (daily walking), respiratory training (forced deep inspiration with spirometer device), as well as anxiolytic group psychotherapy.; Other Names: Prehabilitation
Active Comparator: ERAS + nutritional prehabilitation; Each patient will be treated in an ERAS program preoperatively. No specific preoperative training will be involved apart from nutritional status assessment and nutritional supplements.	Procedure: ERAS + nutritional prehabilitation; Enhanced Recovery Program, including preoperative 4 weeks nutritional supplementation.; Other Names: Enhanced Recovery After Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity (early) classified after Clavien-Dindo.	7-day morbidity will be detailed assessed. Grade 3 or above morbidity rate will be assessed.	7 days (until 8th postoperative day) postoperative
Morbidity (long term) classified after Clavien-Dindo.	30-day morbidity will be detailed assessed. Grade 3 or above morbidity rate will be assessed.	30 days (until 31st postoperative day)
Change in preoperative functional status - 6MWD by operation	6MWD (6-minute walking distance test)	Measured points: 4 weeks before surgery, on day of hospital admission
Change in postoperative functional status - 6MWD by the end of rehabilitation	6MWD (6-minute walking distance test)	Measured points: 4 weeks before surgery, 8 weeks after operation
Length of hospital stay	Postoperative length of hospital stay in days.	45 days
Number of days spent on ICU (Intensive care unit).	Number of days observed on ICU right after operation.	45 days
30-day mortality	30-day mortality of each patient will be recorded.	30 days (until 31st postoperative day)
90-day mortality	90-day mortality of each patient will be recorded.	90 days (until 91st postoperative day)
Change in preoperative functional status - FVC by operation	Measured points: 4 weeks before surgery, on day of hospital admission	Measured points: 4 weeks before surgery, on day of hospital admission
Change in preoperative functional status - FVC by the end of rehabilitation	Measured points: 4 weeks before surgery, 8 weeks after operation	Measured points: 4 weeks before surgery, 8 weeks after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of alpha- and beta-diversity of fecal microbata	Fecal microbara diversity will be measured at diagnosis, at the time of operation and 8 weeks after operation. We will assess diversity changes related to the intervention.	Measured points: 4 weeks before surgery, on day of hospital admission and 8 weeks after surgery

Collaborators and Investigators

• Sponsor: St. Borbala Hospital
• Collaborators: Biological Research Centre, Szeged

Publications and helpful links

General Publications

• Molenaar CJ, van Rooijen SJ, Fokkenrood HJ, Roumen RM, Janssen L, Slooter GD. Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery. Cochrane Database Syst Rev. 2022 May 19;5:CD013259. doi: 10.1002/14651858.CD013259.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): August 7, 2022
• Study Completion (Estimated): June 7, 2024

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: prehabilitation; ERAS; fecal microbata
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: ERASvsPrehab_2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 10 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

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