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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain; Endometriosis; Pain, Acute; Pain, Acute Postoperative
• Intervention / Treatment: Drug: Clonidine; Drug: Isotonic saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Stine Birkebaek, MD; Phone Number: 0045 53655024; Email: stibir@rm.dk
• Study Contact Backup: Name: Lone Nikolajsen, MD, DMSc; Phone Number: 7846 4317; Email: Lone.nikolajsen@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Stine Birkebaek, MD; Phone Number: 0045 53655024; Email: stibir@rm.dk
    • Principal Investigator: Stine Birkebaek, MD
    • Contact: Lone Nikolajsen, PhD, DMSc; Phone Number: 7846 4317; Email: Lone.nikolajsen@clin.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 108 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clonidine; 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; A single dose of intraoperatively administered intravenous clonidine 150 μg will be infused over 5-10 min., immediately after intubation
Placebo Comparator: Isotonic saline; 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; A single dose of administered intravenous isotonic saline will be infused over 5-10 min., immediately after intubation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Chair: Lone Nikolajsen, MD, DMSc, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Pain, Postoperative; Endometriosis; Acute Pain; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: 2022064017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data will be shared upon reasonable request by other researchers

Drug and device information, study documents

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