The Immunomodulatory Effect of Sugammadex After Total Hip Replacement Surgery Under Neuraxial Anaesthesia: a Pilot Study (MAGIC)

Monocenter randomized controlled proof of principle study to investigate the effect of sugammadex at the end of total hip replacement surgery on the postoperative innate immune function

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Hip; Innate Inflammatory Response
• Intervention / Treatment: Drug: Sugammadex 100 MG/ML [Bridion]; Other: Placebo

Detailed Description

Rationale: With infections being the number one complication after surgery, more research is aimed at therapeutic strategies that positively influence the postoperative immune dysregulation. In the search for reducing surgical stress by a deep neuromuscular block (NMB), our group recently found evidence that sugammadex, used to antagonize a deep NMB, may have an immunomodulatory effect. Ex vivo analysis showed that sugammadex counteracted the immunosuppressive effect of rocuronium, but even in absence of rocuronium it had a positive effect on cytokine production capacity.

Therefore, we now propose a clinical pilot study in patients planned for total hip surgery under neuraxial anaesthesia to further investigate whether sugammadex has beneficial immunomodulatory effects.

Primary objective: To investigate the effect of sugammadex on the postoperative innate immune function.

Study design: A blinded, randomized controlled pilot study

Study population: 20 adults scheduled for primary hip replacement surgery under neuraxial anaesthesia.

Intervention: Patients will be randomized between a group receiving sugammadex at the end of surgery and a group receiving placebo.

Primary endpoint: Postoperative innate immune function as reflected by ex vivo mononuclear cell cytokine production capacity upon whole blood lipopolysaccharide (LPS) stimulation.

Secondary endpoint: Postoperative innate immune function as reflected by DAMP release and circulating inflammatory cytokines, Quality of Recovery score (QoR-40) postoperative day 1, postoperative pain and analgesia consumption, 30-day postoperative (infectious) complications

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500HB
    • Radboudumc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age of 18 years or older
• Scheduled for total hip replacement surgery under neuraxial anesthesia
• Scheduled for primary hip replacement surgery
• Informed consent obtained

Exclusion Criteria:

• Insufficient control of the Dutch language to read the patient information and to fill out the questionnaires
• Mentally incapacitated patients
• Known or suspected hypersensitivity to sugammadex
• Deficiency of vitamin K dependent clotting factors or coagulopathy
• Severe renal disease (creatinine clearance <30 ml/min), including patients on dialysis)
• Severe liver disease (Child-Pugh Classification C)
• Women who are or may be pregnant or currently breastfeeding
• Women of childbearing potential who don't use adequate method of contraception
• Severe vertebral column disorder
• Chronic use of psychotropic drugs
• Known hypertrophic obstructive cardiomyopathy, severe aortic valve stenosis or severe mitral valve stenosis
• Chronic use of NSAID's, steroids or immunosuppressive drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sugammadex; Sugammadex administration at the end of surgery	Drug: Sugammadex 100 MG/ML [Bridion]; 8 mg/ml; Other Names: Bridion
Placebo Comparator: Placebo; Placebo administration at the end of surgery	Other: Placebo; Sodium 0.9% 5 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative innate immune function	Ex vivo cytokine production capacity (TNF-α, IL-6, IL-10, IL-1β) of mononuclear cells upon whole blood Lipopolysaccharide(LPS) stimulation	Postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative innate immune function	Ex vivo cytokine production capacity (TNF-α, IL-6, IL-10, IL-1β) of mononuclear cells upon whole blood Lipopolysaccharide(LPS) stimulation	2 timepoints: At the start of surgery (±30 minutes after administration neuraxial anesthesia) and at the end of surgery (15 minutes after administration intervention/placebo medication)
Postoperative innate immune function	Circulating inflammatory cytokines (TNF-α, IL-6, IL-10)	3 timepoints: Postoperative day 1, at the start of surgery (±30 minutes after administration neuraxial anesthesia) and at the end of surgery (±15 minutes after administration intervention/placebo medication)
Postoperative innate immune function	Danger associated molecular pattern (DAMP) release (Heat shock protein 70 (HSP 70), High mobility group box 1 (HMGB1))	3 timepoints: Postoperative day 1, at the start of surgery (±30 minutes after administration neuraxial anesthesia), and at the end of surgery (±15 minutes after administration intervention/placebo medication)
Pain and total analgesia consumption	Pain scores by numeric rating scale (NRS 0-10)	During hospital admission up to 3 days postoperative
Quality of Recovery	Quality of Recovery 40 (QoR-40) validated questionnaire score. 40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)	Postoperative day 1
Postoperative complications	postoperative complications scored by Clavien-Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)	Postoperative day 30
Postoperative infectious complications	Postoperative infectious complications scored the definitions of the StEP-COMPAC group initiative	Postoperative day 30

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Actual): November 23, 2023
• Study Completion (Actual): November 23, 2023

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 10, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Inflammation; Osteoarthritis, Hip
• Other Study ID Numbers: NL82808.091.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be analyzed for publication. After that it belongs to Radboud umc where other researchers of Radboud umc may or may not include this database to their study. But there will be no active sharing

Drug and device information, study documents

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