Evaluation of Post-operative Biochemical Recurrence in Patients Submitted to Radical Prostatectomy Under General Opioid-free Anesthesia Compared to Conventional General Anesthesia

The use of opioids facilitates angiogenesis and has a proven action in the immune system, mainly in the reduction of natural killer cell activity, favoring the migration of neoplastic cells and inhibiting humoral and cellular immunity. These factors may contribute to recurrence and tumor metastasis.

Therefore, could opioid-free anesthesia help reduce tumor recurrence? This is a prospective randomized controlled clinical trial in which patients undergoing radical prostatectomy will be evaluated by conventional means, which have moderate and high D'Amico criteria for tumor recurrence.

In the operating room, patients will be monitored, receive peripheral venoclysis and then randomized into two groups: in group I, the anesthetic induction will be done with pre oxygenation with 100% O2, propofol, cisatracurium, lidocaine and fentanyl; In group II the induction will be done with the same doses of propofol, cisatracurium, lidocaine and placebo.

In both groups maintenance of general anesthesia will be with propofol 1% target infusion controlled with model of Marsh target-controlled infusion plasma between 2.0 and 3.0 mcg / ml, ketamine, lidocaine and dexmedetomidine.

Both groups will receive blockade of the transverse plane of the ultrasound guided ultrasound, group I with placebo (saline 0.9% 20 ml on each side) and group II with ropivacaine 0.375% 20 ml on each side. And the postoperative analgesia will be based on anti-inflammatory and opioid analgesics (pca of morphine) according to the analgesic pain scale of the patients.

In the postoperative period, patients will be followed up for 2 years with serial doses of prostate specific antigen (PSA) to diagnose tumor recurrence (2 PSA measures> 0.2 ng / ml) and will be evaluated in relation to analgesia, need for analgesia of Rescue with morphine, satisfaction with the anesthetic technique, adverse effects (nausea and vomiting).

The primary objective is to evaluate tumor biochemical recurrence after radical prostatectomy in patients undergoing opioid anesthesia compared to patients anesthetized without opioids. The secondary objectives are to evaluate the quality of analgesia with the two techniques, patient satisfaction with perioperative period, quality of anesthetic recovery and adverse effects (nausea and vomiting, pruritus and drowsiness).

Thus, to answer the hypothesis raised, 146 patients will be needed (73 in each group).

Study Overview

• Status: Unknown
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: opioid-free group; Procedure: transversus abdominal plane block with ropivacaine; Drug: Opioid Group; Procedure: transversus abdominal plane block with placebo

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 01246-903
      • Instituto do Cancer do Estado de Sao Paulo - ICESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Prostate Cancer;
• Intermediate to high risk of recurrence by D'Amico criteria (Gleason scale > or = 7; PSA > or = 10)

Exclusion Criteria:

• Patient refuse;
• atrioventricular blockade;
• Coagulopathy;
• Other procedure at same time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opioid-free; The patients of this group will receive opioid-free anesthesia	Drug: opioid-free group; We'll study if the opioid-free anesthesia can reduce the biochemical recurrence of prostate cancer.; Procedure: transversus abdominal plane block with ropivacaine; The opioid-free group will receive transversus abdominal plane block with ropivacaine 0,375% 20 ml each side
Active Comparator: Non opioid-free; The patients in this group will receive the same induction and maintenance drugs of the experimental group but with fentanyl 3 - 5 mcg/kg on induction and during the procedure as needed.	Drug: Opioid Group; This group will receive fentanyl in the induction of anesthesia.; Procedure: transversus abdominal plane block with placebo; the non-opioid free group will receive transversus abdominal plane block with physiological solution 0,9% 20 ml each side

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical recurrence of prostate cancer	It's going to be measured the prostate specific antigen in 4 times after the date of the surgery( 6 months, 1 year, 1 and a half year and 2 years after the surgery) to compare elevations between the two groups.	Up to 2 years after the date of the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil-to-lymphocyte ratio	Compare the peutrophil-to-lymphocyte ratio preoperatively and with 24 hour postoperatively between the two groups to study about inflammation.	24 hour postoperatively
visual analogue pain score in the post-anaesthesia care unit	Compare the pain scale between the two groups in the delivery of post-anaesthesia care unit	Up to 2 hours postoperatively
Rescue Morphine	compare the total dosis needed for pain at delivery post-anaesthesia care unit	Up to 2 hours postoperatively
Satisfaction with anesthesia technique	compare the satisfaction (a scale from 01 to 10) with anesthesia technique between the two groups at delivery of post-anaesthesia care unit	Up to 2 hours postoperatively
adverse outcomes	compare the postoperative adverse outcomes (such as nausea, pruritus, somnolence) between the two groups at delivery of post-anaesthesia care unit	Up to 2 hours postoperatively

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo

Publications and helpful links

General Publications

• Rangel FP, Auler JOC Jr, Carmona MJC, Cordeiro MD, Nahas WC, Coelho RF, Simoes CM. Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial. Br J Anaesth. 2021 May;126(5):931-939. doi: 10.1016/j.bja.2021.01.031. Epub 2021 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2017
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: July 6, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: general anesthesia; cancer recurrence; neoplasm; opioids analgesics
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Narcotics; Anesthetics, Local; Ropivacaine; Analgesics, Opioid
• Other Study ID Numbers: NP 834/15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The following data will be available: which group the patient were randomized; BMI; PSA preoperatively, 6 months, 1 year, 1,5 year and 2 years; prostate volume; gleason scale; neutrophil-to-lymphocyte ratio preoperatively and postoperatively; bleeding; intraoperative hydration; amount of opioids in the intraoperative period; VAS pain scale in the PACU and morphine dosis in the PACU

Drug and device information, study documents

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