Clinical trial NCT04595604: Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery.
Official title: Long Term Effect of Trimodal Prehabilitation Compared to ERAS in Colorectal Cancer Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Cancer
Keywords: ERAS
prehabilitation
fecal microbata
Lead sponsor: St. Borbala Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Biological Research Centre, Szeged
First posted: 2020-10-20
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients planned for elective, curative operations for colorectal cancer will be randomized into two groups: experimental group will take part in a dedicated 4-week multimodal preparation program followed by ERAS preoperative management, while control group will just participate in the ERAS program without specific physical and mental preparation.

2:1 randomization will be performed for interventional and control arm
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Length of hospital stay
timeFrame: 45 days
measure: Number of days spent on ICU (Intensive care unit).
timeFrame: 45 days
measure: Morbidity (early) classified after Clavien-Dindo.
timeFrame: 7 days (until 8th postoperative day) postoperative
measure: Morbidity (long term) classified after Clavien-Dindo.
timeFrame: 30 days (until 31st postoperative day)
measure: 30-day mortality
timeFrame: 30 days (until 31st postoperative day)
measure: 90-day mortality
timeFrame: 90 days (until 91st postoperative day)
measure: Change in preoperative functional status - 6MWD by operation
timeFrame: Measured points: 4 weeks before surgery, on day of hospital admission
measure: Change in postoperative functional status - 6MWD by the end of rehabilitation
timeFrame: Measured points: 4 weeks before surgery, 8 weeks after operation
measure: Change in preoperative functional status - FVC by operation
timeFrame: Measured points: 4 weeks before surgery, on day of hospital admission
measure: Change in preoperative functional status - FVC by the end of rehabilitation
timeFrame: Measured points: 4 weeks before surgery, 8 weeks after operation
Secondary outcomes:
measure: Change of alpha- and beta-diversity of fecal microbata
timeFrame: Measured points: 4 weeks before surgery, on day of hospital admission and 8 weeks after surgery
Other outcomes:
Locations:
city: Tatabánya
country: Hungary
facility: Department of Surgery, St. Borbala Hospital
city: Tatabánya
country: Hungary
facility: St. Borbala Hospital
Study officials:
References:
citation: 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(5):CD013259. doi: 10.1002/14651858.CD013259.pub2.