Clinical trial NCT05723406: The Immunomodulatory Effect of Sugammadex After Total Hip Replacement Surgery Under Neuraxial Anaesthesia: a Pilot Study
Official title: The Immunomodulatory Effect of Sugammadex After Total Hip Replacement Surgery Under Neuraxial Anaesthesia: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Innate Inflammatory Response
Osteoarthritis, Hip
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2023-02-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Postoperative innate immune function
timeFrame: Postoperative day 1
Secondary outcomes:
measure: Postoperative innate immune function
timeFrame: 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)
measure: Postoperative innate immune function
timeFrame: 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)
measure: Postoperative innate immune function
timeFrame: 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)
measure: Pain and total analgesia consumption
timeFrame: During hospital admission up to 3 days postoperative
measure: Quality of Recovery
timeFrame: Postoperative day 1
measure: Postoperative complications
timeFrame: Postoperative day 30
measure: Postoperative infectious complications
timeFrame: Postoperative day 30
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
References: