HIPPO: Impact of Deep Neuromuscular Blockade During Total Hip Replacement Surgery on Postoperative Recovery and Immune Function

Sponsor
Radboud University Medical Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT05562999
Collaborator
Merck Sharp & Dohme LLC (Industry)
100
1
2
17.4
5.7

Study Details

Study Description

Brief Summary

Monocenter randomized controlled trial to compare the effect of deep neuromuscular blockade (NMB) versus moderate NMB during total hip replacement surgery on postoperative quality of recovery and innate immune function.

Condition or Disease Intervention/Treatment Phase
  • Drug: Rocuronium Bromide
  • Drug: Rocuronium Bromide
Phase 4

Detailed Description

Rationale: Neuromuscular blockade agents (NMB) may enable surgeons to optimize exposure during hip surgery. With an increasing depth of NMB, manipulation of muscles and adjunctive tissues may be easier, therefore reducing damage to muscles and adjunct tissues. Accumulating evidence exists that the use of deep NMB in laparoscopic surgery is associated with a better quality of recovery and lower pain scores. However, whether this accounts for open surgery is still unknown.

In addition, surgery is associated with postoperative immune suppression. Surgical stress and damage cause the release of Danger Associated Molecular Patterns (DAMPs). After trauma and sepsis, the release of DAMPs is associated with immune paralysis and a higher susceptibility to infectious complications. Previous research indicates that DAMPS are the origin of postoperative immune suppression. The use of deep NMB in hip surgery may reduce surgical damage and thereby lead to a better quality of recovery and secondarily a better preservation of immune cell function.

Primary objective: To establish the relationship between the use of deep neuromuscular blockade (NMB) versus moderate NMB and the quality of recovery after total hip replacement surgery (THR) Secondary objective: To establish the relationship between the use of deep NMB versus moderate NMB and innate immune function after THR surgery

Study design: A monocenter, blinded, randomized controlled clinical trial

Study population: adults who are scheduled for primary or secondary hip replacement surgery under general anaesthesia.

Intervention: Patients will be randomized between a deep NMB (post tetanic count (PTC) 1-2) and moderate NMB (Train-of-four (TOF) 1-2)

Primary endpoint: Quality of Recovery score (QoR-40) at postoperative day 1.

Secondary endpoints: postoperative innate immune function, QoR-40 at postoperative day 30, 30-day postoperative (infectious) complications, postoperative pain scores and opioid consumption

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
Deep Versus Moderate Neuromuscular Blockade During Total HIP Replacement Surgery to Improve POstoperative Quality of Recovery and Immune Function: a Randomized Controlled Study
Actual Study Start Date :
Nov 18, 2022
Anticipated Primary Completion Date :
May 1, 2024
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Deep neuromuscular blockade

Participant will receive deep neuromuscular blockade (PTC 1-2)

Drug: Rocuronium Bromide
Deep NMB (PTC 1-2)
Other Names:
  • Bridion
  • Active Comparator: Moderate neuromuscular blockade

    Participant will receive moderate neuromuscular blockade (TOF 1-2)

    Drug: Rocuronium Bromide
    Moderate NMB (TOF 1-2)
    Other Names:
  • Bridion
  • Outcome Measures

    Primary Outcome Measures

    1. Quality of Recovery 40 (QoR-40) questionnaire score [Postoperative day 1]

      40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)

    Secondary Outcome Measures

    1. Quality of Recovery 40 (QoR-40) questionnaire score [Postoperative day 30]

      40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)

    2. Immune function represented by serum cytokine [Postoperative day 1]

      Serum cytokine IL-6 level

    3. Immune function represented by IL-10 [Postoperative day 1]

      Serum cytokine IL-10 level

    4. Immune function represented by TNF-a [Postoperative day 1]

      Serum cytokine TNF-a level

    5. Immune function represented by ex-vivo IL-6 production capacity [Postoperative day 1]

      Ex-vivo IL-6 production capacity upon whole blood Lipopolysaccharide(LPS) stimulation

    6. Immune function represented by ex-vivo IL-10 production capacity [Postoperative day 1]

      Ex-vivo IL-10 production capacity upon whole blood LPS stimulation

    7. Pain score by numeric pain rating (NRS) scale [During hospital admission up to 3 days postoperative]

      pain scores with NRS 0 (no pain) to 10 (severe pain)

    8. Postoperative complications [30 postoperative days]

      postoperative complications scored by Clavien-Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)

    9. Infectious postoperative complications [30 postoperative days]

      Postoperative infectious complications scored the definitions of the StEP-COMPAC group initiative

    10. Analgesia consumption [During hospital admission up to 3 days postoperative]

      non-cumulative and cumulative opioid use per day in morphine equivalent

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age of 18 years or older

    • Scheduled for total hip replacement surgery under general anaesthesia

    • Informed consent obtained

    Exclusion Criteria:
    • Insufficient control of the Dutch language to read the patient information and to fill out de questionnaires

    • Known or suspected hypersensitivity to rocuronium or 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)

    • Known or suspected neuromuscular disorders impairing neuromuscular function

    • Women who are or may be pregnant or currently breastfeeding

    • Chronic use of psychotropic drugs

    • Use of immunomodulatory medication

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Radboudumc Nijmegen Netherlands 6500HB

    Sponsors and Collaborators

    • Radboud University Medical Center
    • Merck Sharp & Dohme LLC

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Radboud University Medical Center
    ClinicalTrials.gov Identifier:
    NCT05562999
    Other Study ID Numbers:
    • NL81931.091.22
    First Posted:
    Oct 3, 2022
    Last Update Posted:
    Jan 10, 2023
    Last Verified:
    Sep 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 10, 2023