Intraoperative Clonidine for Postoperative Pain Management in Patients Undergoing Surgical Treatment for Endometriosis

Study Overview
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Brief Summary
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The role of a single dose of intraoperative clonidine on postoperative opioid requirements, pain intensity and opioid-related side effects in patients undergoing surgical treatment for endometriosis remains scarcely explored. A prospective double-blind, randomised controlled trial investigating the effect of a single-dose of intraoperative clonidine in patients undergoing surgical treatment for endometriosis is therefore conducted.

Detailed Description
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Background with aim: Acute postoperative pain is a major and common concern for the large number of patients who undergo surgery each year. Despite advances in pain management strategies, many patients continue to suffer from moderate-to-severe pain during the early postoperative period. This is concerning as unrelieved pain can result in decreased patient satisfaction, increased morbidity, prolonged hospital length-of-stay and increased risk of persistent pain. Effective treatment of acute postoperative pain should therefore be prioritized. Opioid analgesics remain the mainstay treatment for postoperative pain. The potential benefits of opioid therapy for acute pain are short-term pain control. However, there are several potential harms associated with opioid use which may outweigh the benefits including sedation, nausea, vomiting, constipation and risk of long-term use. In this respect, a single dose of clonidine could provide stable analgesia and potentially reduce the need for shorter-acting opioids. Therefore, the investigators decided to carry out the present study with the aim to examine the analgesic efficacy and safety of intraoperatively administered intravenous clonidine in patients undergoing surgical treatment for endometriosis on postoperative opioid consumption, pain intensity and opioid-related side effects. Method: 120 patients undergoing surgical treatment for endometriosis will be included in this prospective, randomized, double-blind, controlled trial with two arms: an intervention arm (clonidine 150 microgram) and a control arm (isotonic saline). The study will be GCP-monitored, and is approved by the Danish Medicines Agency (2022064017) and the National Committee on Health Research Ethics (2209269). Hypothesis: The investigators hypothesize that a single dose of intraoperatively administered intravenous clonidine will be effective in reducing postoperative opioid requirements, pain intensity and opioid-related side effects.

Official Title
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Intraoperative Clonidine for Postoperative Pain Management in Patients Undergoing Surgical Treatment for Endometriosis: a Prospective, Double-blind, Randomized Controlled Trial

Conditions
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Endometriosis, Postoperative Pain, Pain, Acute, Pain, Acute Postoperative

Intervention / Treatment
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* Drug: Clonidine
* Drug: Isotonic saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patients scheduled for surgical laparoscopic treatment of endometriosis at Aarhus University Hospital Exclusion Criteria: Age < 18 years American Society of Anesthesiologists (ASA) physical status IV or V Allergy to clonidine Inability to provide informed consent Known severe renal insufficiency Known severe bradyarrhythmia Pregnancy, lactation: Daily opioid consumption the last 7 days before surgery Pain intensity >5 on more than half of the days during the last month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 120 patients undergoing surgical treatment for endometriosis will be included in this prospective, randomized, double-blind, controlled trial with two arms: Intervention arm (clonidine 150 microgram). Control arm (isotonic saline).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clonidine<br>A 100 ml isotonic saline will be mixed with 1 ml clonidine (150 μg). The blinded 100 ml bag including isotonic saline and clonidine 150 μg will be infused over 5-10 min., immediately after intubation. | Drug: Clonidine<br>* A single dose of intraoperatively administered intravenous clonidine 150 μg will be infused over 5-10 min., immediately after intubation<br>|
| Placebo Comparator: Isotonic saline<br>A 100 ml isotonic saline will be mixed with 1 ml isotonic saline. The blinded 100 ml bag including isotonic saline will be infused over 5-10 min., immediately after intubation. | Drug: Isotonic saline<br>* A single dose of administered intravenous isotonic saline will be infused over 5-10 min., immediately after intubation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative opioid consumption 0-3 hours | Opioid consumption within the first 3 hours after arrival at the PACU | 3 hours after arrival at the PACU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative opioid consumption 0-6 hours | Opioid consumption within the first 6 hours after arrival at the PACU | 6 hours after arrival at the PACU | 
| Pain intensity at rest | Pain intensity at rest (NRS; 0-10) at 0, 30, 60, 90 and 120 minutes after arrival at the PACU | 0, 30, 60, 90 and 120 minutes after arrival at the PACU | 
| Pain intensity during coughing | Pain intensity during coughing at 0, 30, 60, 90 and 120 minutes after arrival at the PACU | 0, 30, 60, 90 and 120 minutes after arrival at the PACU | 
| Shivering | Shivering at 0, 60 and 120 minutes after arrival at the PACU | 0, 60 and 120 minutes after arrival at the PACU | 
| Sedation (Ramsey Sedation Score 1-6) | Sedation at 0, 60 and 120 minutes after arrival at the PACU | 0, 60 and 120 minutes after arrival at the PACU | 
| PONV | Nausea and/or vomiting at 0, 60 and 120 minutes after arrival at the PACU | 0, 60 and 120 minutes after arrival at the PACU | 
| Discharge from the PACU | Time for discharge from the PACU (hours and minutes) | 24 hours |