The Effect of Perioperative Dexamethasone Administration on Postoperative Pain in Patients Undergoing Periacetabular Osteotomy. (PAODEX)

The Effect of Perioperative Dexamethasone Administration on Postoperative Pain in Patients Undergoing Periacetabular Osteotomy: A Randomised Double-blind, Placebo-controlled Trial

This is an investigator-initiated, Danish mono-center, randomized, placebo-controlled, parallel group, double-blind, superiority trial of dexamethasone on postoperative pain management on patients undergoing operation for hip dysplasia with the periacetabular osteotomy procedure (PAO). 90 adults undergoing PAO will be enrolled.

The primary outcome is to compare the effect of dexamethasone relative to placebo on cumulated postoperative morphine consumption at 48 hours.

Key secondary outcomes include comparing the effect of repeated doses of dexamethasone relative to a single dose on cumulated postoperative morphine consumption at 48 hours, and to determine if dexamethasone is superior to placebo for: Perception of pain intensity, prevalence and degree of postoperative nausea and vomiting, and patient-reported outcome measures.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Hip Dysplasia; Postoperative Nausea and Vomiting; Dexamethasone
• Intervention / Treatment: Drug: Dexamethasone 24mg Solution for Injection; Drug: Saline Solution for Injection

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Viktoria Lindberg-Larsen, MD, PhD; Phone Number: +45 28791991; Email: viktoria.lindberg-larsen@rsyd.dk
• Study Contact Backup: Name: Stine Hebsgaard, MD; Phone Number: +45 26814697; Email: stine.hebsgaard3@rsyd.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing PAO due to symptomatic hip dysplasia (CE<25grader) or retroverted acetabulum (crossover and posterior wall sign)
• ≥ 18 years
• Females if fertile: Verified negative human chorionic gonadotropin (HCG), usage of safe contraceptives or surgical sterilisation.
• Patients who give their written informed consent to participating in the trial, after having fully understood the content of the protocol and restrictions.

Exclusion Criteria:

• Patients who cannot speak or understand Danish
• Allergy or contraindications to trial medication
• Spinal anaesthesia
• Second intervention carried out simultaneously (e.g. femur osteotomy)
• Patients with daily opioid consumption prior to surgery (tramadol and codeine accepted)
• Drug, medical abuse or weekly alcohol consumption beyond ≥7 (female) and ≥14 (men) units, respectively.
• Mental disability, anxiety disorder (active psychiatric disorder or consumption of tricyclic antidepressants)
• Diabetes diagnosed prior to inclusion
• Immune suppression therapy (e.g. systemic glucocorticoids)
• Kidney impairment (eGFR < 50ml/min) or liver disease (≥Child Pugh B)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Dexamethasone twice; 24mg intravenous Dexamethasone (Dexavital®, Vital Pharma) 4mg/ml just before the operation and repeated after 24 hours.	Drug: Dexamethasone 24mg Solution for Injection; Administrated i.v.; Other Names: Dexa
Experimental: B; Dexamethasone once; 24mg intravenous Dexamethasone just before the operation and placebo which is 6ml of isotonic sodium chloride (9mg/ml, 'normal' saline) after 24 hours	Drug: Dexamethasone 24mg Solution for Injection; Administrated i.v.; Other Names: Dexa; Drug: Saline Solution for Injection; administrated i.v.; Other Names: Saline
Placebo Comparator: C; Placebo twice; placebo intravenous just before the operation and repeated after 24 hours	Drug: Saline Solution for Injection; administrated i.v.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulated postoperative morphine consumption in milligrams after 48 hours.	Morphine administered both as patient-controlled analgesia (PCA) i.v. morphine and any other supplemental morphine administered postoperatively. Consumption in mg.	0-48 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain intensity after 48 hours.	Pain is evaluated at rest and under the timed-up-and-go (TUG) procedure. Pain intensity is assessed using the visual analogue scale (VAS) (0-100mm).	24, 48 hours postoperatively
Cumulated postoperative morphine consumption from 48 hours until day 14 post operation	Morphine consumption in milligrams after the operation.	48 hours - day 14 postoperatively
Postoperative nausea and vomiting	Nausea and vomiting are evaluated using a 4 point scale: none, mild, moderate, severe	24 and 48 hours postoperatively
Antiemetic consumption	Evaluation of cumulated antiemetic consumption in mg and drug will be assessed.	0-48 hours postoperatively
Sleep	Sleep quality will be assessed using the VAS scale (0-100)	0-7 days postoperatively
Timed up and go test	Is assessed from; the time that the participant takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down.	24, 48 hours postoperatively
Serious adverse events (SAE)	SAE's including wound infection treated with antibiotics or revision. Patients will be asked for SAE during the intervention period, at a follow-up visit 8 weeks the operation. This will be supplemented with a look up for prescriptions.	0-8 weeks after operation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulated postoperative morphine consumption in milligrams after 24hours.	Morphine administered both as patient-controlled analgesia (PCA) i.v. morphine and any other supplemental morphine administered postoperatively. Consumption in mg.	0-24 hours postoperatively
Cumulated antiemetic consumption	antiemetic consumption in mg and drug will be assessed after 24hrs.	0-24 hours postoperatively
Fasting blood glucose	assessment of fasting blood glucose in mg/mL	0 hours, 6 hours, 24 hours, 48 hours (72 hours)
C-reactive protein (CRP)	blood sample to evaluate the influence of dexamethasone on the postoperative inflammation development.	0, 6, 24, 48 hours (72 hours) postoperatively
Leucocytes	blood sample to evaluate the influence of dexamethasone on the postoperative inflammation development.	0, 6, 24, 48 hours (72 hours) postoperatively
Cytokines	evaluate the decrease of cytokines concentration (Interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF) and pentraxin 3 (PTX3) as markers of response during treatment with Dexamethasone	0, 6, 24, 48 hours (72 hours) postoperatively
Patient reported outcome measure, quality of life	Based on the questionnaire: EuroQol - 5 Dimensions (EQ-5D) after 3 and 6 months and 1 year follow up.	3, 6, 12 months postoperatively
Patient reported outcome measures, health	Patient evaluated health based on the questionnaire: University of California, Los Angeles (UCLA) after 3 and 6 months and 1 year follow up.	3, 6, 12 months postoperatively
Patient reported outcome measures, the Oxford Hip questionnaire	Patient evaluated activity and pain, based on the questionnaire: Oxford Hip after 3 and 6 months and 1 year follow up.	3, 6, 12 months postoperatively

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Odense Patient Data Explorative Network
• Investigators: Study Chair: Viktoria Lindberg-Larsen, MD, PhD, Dept. of Anesthesiology and Intensive Care Medicine, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 31, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: dexamethasone; postoperative pain; pain management
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Wounds and Injuries; Congenital Abnormalities; Signs and Symptoms, Digestive; Joint Diseases; Musculoskeletal Diseases; Hip Injuries; Musculoskeletal Abnormalities; Joint Dislocations; Nausea; Pain, Postoperative; Vomiting; Hip Dislocation; Developmental Dysplasia of the Hip; Hip Dislocation, Congenital; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Pharmaceutical Solutions
• Other Study ID Numbers: SO_SH_01_2019; 2019_000402_30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No