Mepivacaine Versus Low-Dose Bupivacaine For Primary Total Hip and Knee Arthroplasty

Double Blind Randomized Clinical Trial Comparing Time To Return of Lower Extremity Motor Function Following Spinal Anesthetic With Mepivacaine Versus Low-Dose Bupivacaine For Primary Total Hip and Knee Arthroplasty

This research is being done to see if there is a difference between two different spinal anesthetics (Mepivacaine vs. Bupivacaine) as it relates to reducing post-operative complications and the time it takes for subjects to regain mobility after surgery.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Hip Osteoarthritis
• Intervention / Treatment: Drug: Low-Dose Bupivacaine; Drug: Mepivacaine

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physiological status I-III (patient must meet criteria of a status I-III in the ASA Physical Status Classification System: I=Normal Healthy Patient, II=Mild Systemic Disease, and III=Severe Systemic Disease)
• Unilateral primary TKA or THA
• 18+ years of age
• Able to provide informed consent

Exclusion Criteria:

• Chronic pain syndromes such as fibromyalgia or complex regional pain syndrome
• Chronic opioid use (>1 mos) with OME >5 mg/day OR acute opioid use (< 1 mos) with OME > 30 mg/day.
• Body mass index (BMI) > 45 kg/m2
• Severe drug allergy* to medications used in this study, including non-steroidal anti-inflammatory drugs (i.e. celecoxib and ketorolac), and local anesthetics (defined as an immune reaction resulting in shortness of breath, hives, anaphylaxis, wheezing, and fever)

• Major systemic medical comorbidities such as:

  • Pre-existing severe renal disorder defined as glomerular filtration rate (GFR) <50 units/m2 (if labs are available), currently on dialysis, or highly suspected based on history.
  • Severe hepatic disorder defined as current or past diagnosis of acute/subacute necrosis of liver, acute hepatic failure, chronic liver disease, cirrhosis (primary biliary cirrhosis), chronic hepatitis/toxic hepatitis, liver abscess, hepatic coma, hepatorenal syndrome, other disorders of liver
• Contraindication to spinal anesthesia technique (e.g., known spinal stenosis, coagulopathy, sepsis, infection at site of injection, uncooperative, refusal, anticoagulation medications not held within appropriate time frame*). *Per ASRA guidelines, Clopidogrel (Plavix) held for at least 7 days, Dabigatran (Pradexa) held for at least 5 days, Rivaroxaban (Xarelto)held for at least 3 days, Warfarin (Coumadin)held for at least 5 days or recent INR of less than 1.4, Enoxaparin (Lovenox) with doses > 1 mg/kg held for close to 24 hours.
• Known to be currently pregnant or actively breastfeeding. Patients that have a previous history of menopause, hysterectomy, or tubal ligation will not be required to perform a pregnancy test. Female patients that do not meet this criterion will be asked to submit a urine sample, and will require a negative urine sample in order to proceed with study protocol. Urine sample be collected pre-procedurally.
• Impaired cognition

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
Active Comparator: Low-Dose Bupivacaine; Subjects in this group will be given 10mg of Low-Dose Bupivacaine, which is within standard of care for spinal anesthesia during TKA or THA.	Drug: Low-Dose Bupivacaine; 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic
Active Comparator: Mepivacaine; Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA.	Drug: Mepivacaine; 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Return of Lower Extremity Motor Function	Assessed by measuring time from spinal anesthetic administration to postoperative achievement of Bromage 0 function (return of spontaneous ankle, knee, and hip movement) in the non-operative extremity at 15-minute intervals.	Post surgery, approximately 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Anesthesia Care Unit (PACU) Length of Stay	Number of minutes subjects were admitted to PACU following the surgical procedure	Time of discharge, approximately 1-2 days
Hospital Length of Stay	Number days subjects were admitted to the hospital following the surgical procedure	Time of discharge, approximately 1-2 days
Maximum Pain Score	Measured on a scale from 1 to 10 in the first 24 hours following the surgical procedure, 1=mild pain; 10=worst pain.	24 hours following the surgical procedure
Median Pain Score	Measured on a scale from 1 to 10 in the first 24 hours following the surgical procedure, 1=mild pain; 10=worst pain.	24 hours following the surgical procedure
Discharge Pain Score	Measured on a scale from 1 to 10 at time of hospital discharge, 1=mild pain; 10=worst pain.	Time of discharge, approximately 1-2 days
Orthostatic Hypotension	Number of participants to experience orthostatic hypotension following the surgical procedure.	Time of discharge, approximately 1-2 days
Urinary Retention	Number of participants to experience urinary retention follow the surgical procedure.	Time of discharge, approximately 1-2 days
Transient Neurologic Symptoms	Number of participants to report transient neurologic symptoms	One week post-operative

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Matthew P Abdel, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): October 29, 2019
• Study Completion (Actual): October 29, 2019

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 12, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine; Mepivacaine
• Other Study ID Numbers: 18-008635

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