Clinical trial NCT05631834: ESP Versus TEA for Oeasophagus Cancer Surgery
Official title: Bilateral Asymmetrical Erector Spinae Catheters Analgesia Versus Thoracic Epidural Catheter Analgesia in Minimally Invasive Oesophageal Cancer Surgery: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Peri Operative Analgesia
Lead sponsor: Vinmec Healthcare System
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single centered, open label, randomized controlled trial
Primary purpose: TREATMENT

Brief summary: For esophagectomy, peri-operative continuous thoracic epidural analgesia (TEA) is the standard of care for perioperative pain management. Although effective, TEA is associated with moderate to serious adverse events such as hypotension and neurologic complications. Peri-operative continuous Erector spinae analgesia (ESP) may be a safe alternative. The Investigators hypothesize that TEA and ESP are similar in efficacy for pain treatment in thoracolaparoscopic esophagectomy with less side effects.

Methods. This Randomized prospective randomized study will compare TEA (Which is a wellknown technique of regional anaesthesia with numerous publications) with ESP ( Which is a technique of regional anaesthesia described in 2016 and with already 1000 publication) in a consecutive series of 50 thoracolaparoscopic esophagectomies randomized in 2 groups study groups ESP and controled group TEA.

In this study,

* The TEA will consist of continuous epidural ropivacaine and sufen- tanil infusion with an induction dose for the surgery and a programmed intermittent bolus (PIB) started at the end of the surgery and ended 72h after the end of the surgery.
* The ESP; the Bilateral catheters will be inserted under ultrasound guidance after the anaesthesia induction with an induction dose and a PIB started at the end of the surgery and ended 72h after the end of the surgery.

The primary outcome will be the median highest recorded Visual Analogic Scale (VAS) during the 3 days after surgery.

The secondary outcomes will be vaso-pressor consumption, fluid administration, and length of hospital stay.

Detailed description: For this single-center Prospective randomized controlled study, with the Approval of Ethical committee of VinMec Healthcare and after Patient's information waived the need for informed consent. The performance and reporting of this study will be in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Investigators are hypothesizing that intra-operative and post operative Thoracic Epidural analgesia (TEA) or Erector Spinae Plane analgesia (ESP) are similary effective with regard to quality of analgesia in Thoraco Laparoscopic Akiyama oesophagectomy for cancer.

Patients, listed for this type of surgery,after information and signed consent will be randomized via a random number generator into one of two treatment groups by the person who obtained consent which is prescribed in the nurse preparation file".

• Group 1 = Control group will have peri-operative analgesia by standard Continuous TEA. The TEA performance and epidural insertion will be performed just before the anesthesia induction as per guidelines in regional anesthesia. the tip of the epidural cathter should be at the level of the thoracic vertebra (T) 7. Puncture point at level T9

Volume of ropivacaine 0.5% Patient height:

140 - 149 cm = 8 mL 150 - 159 cm = 10 mL 160 - 169 cm = 12 mL 170 - 180 cm = 14 mL \>180 cm = 16 mL without exceeding 3 mg/kg

• Group 2 = Treatment group with have perioperative analgesia by continuous Bilateral ESP catheters. As it is interfascia block the guidelines of regional anesthesia allows to perform under general anesthesia (GA) The ESP performance will be just after inducation of GA on a stable patient. The ESP Performance performance will be under Ultrasound guidance. The tip of catheter will be on the left side at T6 and right side at T7.

Volume of ropivacaine 0.5% Patient height without exceeding 3 mg/kg 140 - 149 cm = 8 mL / left side - 6 mL / right side 150 - 159 cm = 10 mL / left side - 8 mL / right side 160 - 169 cm = 120 mL / left side - 10 mL / right side 170 - 179 cm= 14 mL / left side - 12 mL / right side \> 180 cm = 16 mL / side - 14 mL / right side

After the surgery the patient will be extubated as soon as possible in the operating room and transferred to the intensive care unit for closed monitoring the post operative analgesia will Combined:

1. Paracetamol 15 mg/kg/dose every 8 h
2. Regional analgesia Ropivacaine 0,2% without exceeding 8mg/kg-24h. Group 1 TEA PIB every 4 hours 140 - 149 cm = 8 mL 150 - 159 cm = 10 mL 160 - 169 cm = 12 mL 170 - 180 cm = 14 mL \>180 cm = 16 mL Group 2 ESP 140 - 149 cm = 8 mL / left side - 6 mL / right side 150 - 159 cm = 10 mL / left side - 8 mL / right side 160 - 169 cm = 120 mL / left side - 10 mL / right side 170 - 179 cm= 14 mL / left side - 12 mL / right side \> 180 cm = 16 mL / side - 14 mL / right side
3. PCA morphine connected to the patient

   * Concentration Morphine : 50 mg/49 ml + Ketamine 50 mg
   * Loading dose: 1mg
   * PCA dose demand: 1 mL/dose
   * Lockout: 10 min
   * Continuous rate (basal): 0
   * Dose limit (hr): 6mg/hour Regional analgesia will be interrupted 72h after the induction of general anesthesia Analgesia will be

     * Paracetamol 500 mg x 3/day (Maximum 15mg/kg x 3 /day)
     * Arcoxia 60 mg BD
     * If pain = Ultracet maximum 3 per day

Control of plasmatic dosage ropivacaine 24h 48h 72h after induction ESP and 40 minutes after last PIB

Data collection will start just after induction of regional anaesthesia for both group up to 72h after the induction of the general anaesthesia

Statistical analysis The study is a non-inferiority trial. Two groups of patients scheduled for thoracoscopic oesophagectomy and receiving a TEA or ESP regional analgesia regimen were randomized and compared. As a non-inferiority trial, a per protocol analysis is mandatory. We consider that a patient non receiving a regional analgesia technique during the entire 72h postoperative period or non receiving the PCA morphine as a rescue analgesia technique will be dropped out from the study for the primary outcome. The primary outcome is the total consumption of morphine during the first three post-operative days. Secondary end points are daily consumption of morphine, pain values at rest and during movement measured with visual analogue scales, QOL 15 analysis at day 3 and at the end of the hospital stay, and specifically the adverse events related to both regional analgesia techniques.

Sample size Considering the study of Kigma and colleagues (ref), the patients receiving a TEA for scopic oesophagectomy reported a MME consumption at 24h 14 mg for the whole 72h postoperative period. We hypothesize no difference (0 mg) between groups (i.e, standard (TEA) group and experimental (ESP) group). The hypothesis is that the amount of morphine needed in the ESP group is not higher but instead similar or less than that in the TEA group. If there is truly no difference between the standard (TEA) and experimental (ESP) treatment, then 25 patients are required with a 80% power (ß risk) for a lower limit of a one-sided 97.5% confidence interval (or equivalently a 95% two-sided confidence interval) to be below the non-inferiority limit of +10 (see table of sample size calculations). Assuming loss of follow-up is approximately 10%, a total of 28 patients are needed for both groups The primary end point will be the total consumption of morphine as rescue analgesia at the end of the first 72 postoperative hours. The T-test will be used to test the non-inferiority comparing the difference (µ2- µ1) to a non-zero quantity M. The assumptions of the t-test are: 1. The data are continuous (not discrete). 2. The differences follow a normal probability distribution. 3. The study sample is a simple random sample from its population. Each individual in the population has an equal probability of being selected in the sample. A Man Whitney test will be used if the data are nonparametric.

For the secondary end points, linear mixed effect models will be used taking into account repeated measures in the same patient (group, time and patient effect), such as for plasma concentration of ropivacaine, the daily amount of Ropivacaine, . Fisher test will be used for the comparison of categorical variables such as adverse events) . Mann Whitney test will be used for the endpoints mentionned above.

Switching to superiority hypothesis If the confidence interval for the difference between both groups (µ2- µ1) lies entirely below 0, then it is acceptable to calculate the P-value associated with a test of superiority and to evaluate whether this is sufficiently small to reject convincingly the hypothesis of no difference. There is no multiplicity argument that affects this interpretation because, in statistical terms, it corresponds to a simple closed test procedure. Usually this demonstration of a benefit is sufficient on its own, provided the safety profiles of the new intervention and the comparator are similar.

All statistical tests are 2 sided with significant level of 0.05. All analysis will be done with latest version of R statistical software. For the first 3 postoperative days, data will be recorded during routine patient rounds done by the anesthesia team in the ICU and surgical ward. Another set of data will be recorded after one month, during routine patient follow-up.

The study will be performed in accordance with the ethical principles that originated from the Declaration of Helsinki, ICH GCP, and all applicable regulations.

Participant Information and Consent A written informed consent shall be obtained from each participant before entering the study or performing any unusual or nonroutine procedure that involves risk to the participant.

Before recruitment and enrollment, each prospective participant or his or her legal guardian will be given a full explanation of the study, allowed to read the approved Information consent form (ICF), and allowed to have any questions answered. Once the investigator is assured that the participant/legal guardian understands the implications of participating in the study, the participant/legal guardian will be asked to give consent to participate in the study by signing the ICF. The authorized person obtaining the informed consent will also sign the ICF.

Eligibility criteria: Inclusion Criteria:

* Patients who are diagnosed with esophageal cancer and scheduled to for TLE using Akiyama technique,
* Informed and signed the consent

Exclusion Criteria:

* patient refusal,
* allergy to local anesthetic (LA),
* complex congenital malformation,
* mental deficit,
* substance abuse (alcohol, opioids, etc.)
* renal insufficiency

Primary outcomes:
measure: Morphine consumption
timeFrame: 72 hours
Secondary outcomes:
measure: Extension of sensory blockade
timeFrame: 72hours
measure: Side effects
timeFrame: 72hours
measure: quality of recovery
timeFrame: 1 week
Other outcomes:
Locations:
Study officials:
affiliation: Vinmec Healthcare System
name: Philippe Macaire, MD
role: PRINCIPAL_INVESTIGATOR
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