Clinical trial NCT06783244: Low Versus Standard Intraabdominal Pressure in Robot-assisted Colorectal Cancer Surgery
Official title: Low Versus Standard Intraabdominal Pressure in Robot-assisted Colorectal Cancer Surgery: A Double Blinded Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Keywords: Colorectal cancer
robot-assisted surgery
intraabdominal pressure
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2025-01-20
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to investigate the influence of low intraabdominal pressure (compared to standard intraabdominal pressure) during robot-assisted colorectal cancer surgery on patients wellbeing after surgery. Patients included are diagnosed with colon- or rectal cancer, and scheduled for curatively intended surgery. The main question the trial aims to answer is:

Does low intraabdominal pressure during robot-assisted colorectal cancer surgery increase the patients wellbeing after surgery?

Researchers will compare low intraabdominal pressure (8 mmHg) to standard intraabdominal pressure (12 mmHg) to see if there is a difference in quality of recovery scores, pain scores and analgetic consumption.

Participants will be asked to fill out the Quality of Recovery 15 (QoR15) questionnaire 8 hours, 24 hours and 48 hours after surgery. Furthermore, patients will be asked to evaluate abdominal pain and shoulder tip pain using the visual analog scale (VAS).

Detailed description: 1. Introduction

   Colorectal cancer is the third most frequent malignancy worldwide with an increasing incidence. Surgical resection is considered the gold standard for the cure of colorectal cancer. It is well recognized that an uneventful postoperative course is pivotal for a favorable prognosis. The length of stay (LOS) after colorectal cancer surgery has traditionally been between 1 and 2 weeks after surgery. This period has rightfully received considerable attention, and in the 2000s, Enhanced Recovery after Surgery (ERAS) protocols emerged as evidence-based perioperative practice guidelines designed to optimize the postoperative outcome and thereby shorten LOS. The ERAS principle is based on multimodal strategies, which collectively accelerates recovery and helps patients return to their baseline physical function more rapidly. ERAS has significantly reduced LOS without compromising patient safety or satisfaction. Minimally invasive surgery (MIS), including laparoscopic and robot-assisted techniques, is now an integral part of modern ERAS and a cornerstone of colorectal cancer surgery.

   In general, MIS has been proven to reduce morbidity, postoperative pain and analgesic consumption, duration of hospital stay and patient satisfaction after colectomy. To ensure proper visceral exposure during minimal invasive surgery CO2 needs to be insufflated into the abdominal cavity. However, the insufflation and the inevitable increased intraabdominal pressure has been associated with postoperative shoulder pain and deep abdominal pain. The standard level of intraabdominal pressure is set around 12 mmHg in most situations and lowering the pressure could possibly decrease the morbidity associated with insufflation.

   The first studies investigating the benefits and disadvantages of low-pressure laparoscopic surgery were performed in patients undergoing cholecystectomy and three major meta-analyses have suggested advantages in low-pressure surgery including reduced postoperative pain, analgesic use, and a slight reduction in length of stay.

   There are only few studies on low pressure colorectal surgery and even fewer using the robotic platform, where the increased dexterity improves the surgical conditions in smaller confined spaces, which may be the result of lowering the pressure. Previously, Diaz-Cambronero et al. demonstrated that 78% of these procedures could safely be completed at 8 mmHg.

   In 2021, S. Celarier and colleagues published The PAROS trial, which was the first prospective randomized trial on low (7 mmHg) versus standard (12 mmHg) intraabdominal pressure in laparoscopic colorectal surgery. The length of stay was significantly decreased in the low-pressure group along with postoperative pain and analgesic consumption. They argued that low pressure should become standard of care in laparoscopic colectomy. Furthermore, low intraabdominal pressure did not compromise peri- or postoperative outcomes, operating time, or oncological safety. A year later, the RECOVER study, a randomized controlled trial, re-ported a clear advantage of low (8 mmHg) intraabdominal pressure in combination with deep neuromuscular blockage during laparoscopic colorectal surgery. This combination proved to be safe and improve the postoperative patient-reported quality of recovery.

   A recent systematic review and meta-analysis found no superiority of low- compared with standard/high pressure during laparoscopic colorectal cancer surgery on LOS, however, postoperative pain and analgesic consumption were not investigated.

   Current recommendation is to use the lowest possible intraabdominal pressure allowing suffi-cient exposure of the operative field, rather than using a routine pressure. This recommendation was published more than 20 years ago, however, in the 2018 ERAS Society guideline for Perioperative Care in Elective Colorectal Surgery it was stated that evidence for reducing intraabdominal pressure is low.

   The used standard pressure of 12 mmHg may be higher than necessary, leaving a potential to reduce pressure and thereby facilitate faster recovery with decreased postoperative pain and increased physical well-being at the time of discharge.
2. Objective and perspective

   The objective of the present study is to investigate the role of low intraabdominal pressure during robot-assisted colorectal cancer surgery on immediate postoperative recovery.

   By challenging the practice of using a standard pressure of 12 mmHg, this trial has the potential to optimize postoperative care and patient satisfaction in robot-assisted colorectal cancer surgery, paving the way for advancements beyond ERAS, potentially enabling same day surgery for selected patients with colorectal cancer.
3. Early patient involvement

   Before initiating the trial, a group of surviving patients previously treated for colorectal cancer at our institution, will be invited to take part in a group interview, with the purpose of giving their important view on the selection of the study endpoints including the rationale for the primary endpoint and possible missed endpoints important for the patients.

   This group of patients will be identified in our local cancer database. An equal gender balance will be ensured, younger and elder patients will be represented, and it will furthermore be ensured that both right and left/rectum resection is represented.

   After the study data have been concluded and the data have been analyzed according to the agreed plan, the same group of patients will be invited to participate in a group presentation of the study results and with the opportunity to give their view on how the results should be interpreted.
4. Experimental plan

4.1. Study design

Investigators aim to conduct a multicenter, double blinded, prospective, randomized trial including patients undergoing robotic colorectal cancer resection, involving collaborating departments from Sweden, Norway and Denmark.

Patients scheduled for elective robot assisted colon or rectal cancer resection will be assessed for eligibility and if inclusion criteria are met patients are included after informed consent. Participants will by randomization be included in a low-pressure group (8 mmHg) or a standard pressure group (12 mmHg) and participant will be stratified according to location of the tumor, right or left/rectal.

It is important to underline, that participants included will receive same standardized surgical treatment as if not included. The operational strategy and procedure will be performed due to national guidelines by a certified colorectal cancer surgeon.

4.5 Data collection and storage

A dedicated REDCap database will be created for online registration using an electronic case report form (eCRF). The case report form will obtain data in regard to in- and exclusion criteria, primary and secondary endpoints and general health, i.e. co-morbidities and data regard-ing the specific case peri and post operation.

Only after informed and written consent, data will be collected directly to the database by clinicians involved in the surgical procedure, who thereby have access to the journal. Beyond this, only the applicant, Victoria Rosberg (VR), and supervisor Peter-Martin Krarup (PMK) are authorized to directly access the patient's journal (including electronical journal) for the purpose of retrieving data necessary for the project. VR and PMK are the only individuals with access to any records registered (i.e. CPR numbers) in the database and will therefore be the sole persons authorized to access patient journals after end procedure or discharge in order to retrieve any missing data. Investigators expect to access 200 medical journals in total (see under power calculation).

4.6 Requirements of participating departments

In this study, investigators aim to standardize the perioperative course therefore, participating surgeons should be experts in robotic colorectal surgery and study operations should not be used for training. For insufflation, the AirSeal system (Conmed) should be used to ensure a staple and uniform intraabdominal pressure and minimize differences between centers.

Participating centers should adhere to the latest ERAS protocol including urinary catheter re-moval immediately after surgery, early mobilization, and nutrition (day 0).

4.7 Patient consent, randomization and blinding

The staff and research personnel receive the protocol to identify patients eligible for inclusion. Inclusion of participants is initiated during the pre-operation appointment. The surgeon informs eligible participants regarding the intervention, the purpose of the study and the foreseeable risks and hypothesized benefits. Participants will have the opportunity to get any question an-swered and are free to be accompanied by relatives if wished.

If a patient consent to participation, a signed informed consent will be obtained and kept in an area inaccessible to third parties. Participants will be given a copy of the informed consent and may at all times withdraw their consent. Participants who decide to withdraw their con-sent will still receive the surgical treatment they were planned to undergo, however, without intervention and data will not be collected to the database.

On the day of surgery, the operating nurse will register the patient in the RED Cap database prior to the procedure, and the database will subsequently assign the patient to a randomiza-tion group. Randomization will thereby be performed using a computer-generated randomiza-tion within the Red Cap database, accessible from the operating room. The operating nurse oversees the randomization. After first insufflation and port placement at 12 mmHg, CO2 is exsufflated and randomization is commenced. The view to the pressure monitor blocked for the surgeons by the operating nurse. The nurse changes the pressure according to randomi-zation, standard (12 mmHg) or low (8 mmHg). The operating nurse will, at all times, be able to view the current intraabdominal pressure.

During the operation, the surgeon is at all times allowed to raise the pressure to 12 mmHg if exposure is poor and operational safety is compromised. For participants in the standard pressure group, the nurse will simulate a change in pressure. Blinding is kept. The surgeon can at all time unblind the patient if necessary.

4.8 Power calculation

To detect a clinically significant between-group difference of 10% in the primary endpoint, QoR15, the required sample size was calculated on the following parameters; a mean value in QoR15 of 97, measured six hours postoperatively in a previous study, a standard deviation in outcome of 23 between baseline- and eight hours postoperatively, a power of 80%, and a type I error of 5%. Based on above parameters, 84 participants in each arm (low- versus standard pressure) is required. To account for dropouts, the number of participants is in-creased to 200 (100 in each arm). No interim analysis is planned.

5 Ethical considerations

The study will not commence before approval from the Committee of Health Research Ethics. All participants will need to sign informed consent and can at any time withdraw their consent. All patient data will be processed and stored in accordance with the General Data Protection Regulation (GDPR). Any patient data handled outside of either the encrypted remote-access registry data server or the RED Cap study database will be fully anonymized and han-dled according to appropriate regulations.

5.1 Patient risk assessment

The intervention has previously demonstrated safety in laparoscopic procedures (see introduction). Therefore, it is considered to pose minimal risk to the patient. Furthermore, the intervention is easily reversible, and the surgeon retains the ability to adjust the pressure at any time during the surgery, should it be deemed necessary to ensure safety and maintain operational quality.

Eligibility criteria: Inclusion Criteria:

* age \>18 years
* a diagnosis of colorectal cancer
* scheduled for curative intended robot-assisted resection

Exclusion Criteria:

* BMI above 35
* inability to fulfill QoR15 questionnaire
* construction of a stoma either proactive or permanent
* metastatic cancer disease
* recieving neoadjuvant treatment
* previous multiple abdominal operations defined as 3 or more

Primary outcomes:
measure: Quality of recovery 15 (QoR15) questionnaire 8 hours after surgery
timeFrame: From end of surgery until 8 hours later
Secondary outcomes:
measure: QoR15 questionnaire 24 og 48 hours after surgery
timeFrame: From end of surgery until 24 and 48 hours later
measure: Postoperative pain score
timeFrame: From end of surgery until at 8 hours, 24 hours and 48 hours after surgery
measure: Postoperative opioid consumption
timeFrame: End of surgery until 3 days after surgery. Assessed up to 6 months after surgery.
measure: Change in intraabdominal pressure during surgery
timeFrame: From operation start until end of surgery. Assessed up to 6 months after surgery.
measure: Operation time
timeFrame: From operation start until end of surgery. Assessed up to 6 months after surgery.
measure: Surgeons experience
timeFrame: Assessed immediately after surgery
measure: Postoperative complications
timeFrame: End of surgery until discharge. Assessed up to 6 months after surgery.
measure: Intensive care unit stays
timeFrame: Until 30 days after surgery. Assessed up to 6 months after surgery.
measure: 30-day mortality rate
timeFrame: Until 30 days after surgery. Assessed up to 6 months after surgery.
measure: Length of stay (LOS)
timeFrame: From admission until discharge. Assessed up to 6 months after surgery.
measure: EQ-5D-5L questionnaire
timeFrame: Upon discharge from hospital. Assessed up to 6 months after surgey.
measure: 30-day readmission rates
timeFrame: Until 30 days after surgery. Assessed up to 6 months after surgery.
measure: Patient satisfaction assessment
timeFrame: From end of surgery until participant is discharged. Assessed up to 6 months after surgery.
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Digestive Disease Center, Copenhagen University Hospital, Bispebjerg
Study officials:
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