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

Study Overview
=================
Brief Summary
-----------------
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

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

Official Title
-----------------
The Immunomodulatory Effect of Sugammadex After Total Hip Replacement Surgery Under Neuraxial Anaesthesia: a Pilot Study

Conditions
-----------------
Innate Inflammatory Response, Osteoarthritis, Hip

Intervention / Treatment
-----------------
* Drug: Sugammadex 100 MG/ML [Bridion]
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 |