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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT03838874
• Collaborator: (none)
• Enrollment: 154
• Location: 1
• Arms: 2
• Actual Duration (Months): 8.1
• Patients Per Site Per Month: 19.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis; Hip Osteoarthritis	Drug: Low-Dose Bupivacaine; Drug: Mepivacaine	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 25, 2019
• Actual Primary Completion Date: Oct 29, 2019
• Actual Study Completion Date: Oct 29, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time to Return of Lower Extremity Motor Function [Post surgery, approximately 1 day]

   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.

Secondary Outcome Measures

1. Post-Anesthesia Care Unit (PACU) Length of Stay [Time of discharge, approximately 1-2 days]

   Number of minutes subjects were admitted to PACU following the surgical procedure

2. Hospital Length of Stay [Time of discharge, approximately 1-2 days]

   Number days subjects were admitted to the hospital following the surgical procedure

3. Maximum Pain Score [24 hours following the surgical procedure]

   Measured on a scale from 1 to 10 in the first 24 hours following the surgical procedure, 1=mild pain; 10=worst pain.

4. Median Pain Score [24 hours following the surgical procedure]

   Measured on a scale from 1 to 10 in the first 24 hours following the surgical procedure, 1=mild pain; 10=worst pain.

5. Discharge Pain Score [Time of discharge, approximately 1-2 days]

   Measured on a scale from 1 to 10 at time of hospital discharge, 1=mild pain; 10=worst pain.

6. Orthostatic Hypotension [Time of discharge, approximately 1-2 days]

   Number of participants to experience orthostatic hypotension following the surgical procedure.

7. Urinary Retention [Time of discharge, approximately 1-2 days]

   Number of participants to experience urinary retention follow the surgical procedure.

8. Transient Neurologic Symptoms [One week post-operative]

   Number of participants to report transient neurologic symptoms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Days and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 3, 2018

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Matthew P. Abdel, M.D., Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03838874
• Other Study ID Numbers: 18-008635
• First Posted: Feb 12, 2019
• Last Update Posted: Aug 12, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; Bupivacaine; Mepivacaine

Study Results

Participant Flow

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Period Title: Overall Study
STARTED	80	74
COMPLETED	80	74
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine	Total
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic	Total of all reporting groups
Overall Participants	80	74	154
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.9 (11.8)	67.9 (9.2)	67.9 (10)
Sex: Female, Male (Count of Participants)
Female	46 57.5%	42 56.8%	88 57.1%
Male	34 42.5%	32 43.2%	66 42.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	80 100%	74 100%	154 100%

Outcome Measures

1. Primary Outcome

Title	Time to Return of Lower Extremity Motor Function
Description	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.
Time Frame	Post surgery, approximately 1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Mean (Standard Deviation) [minutes]	210.3 (79.54)	184.7 (47.8)

2. Secondary Outcome

Title	Post-Anesthesia Care Unit (PACU) Length of Stay
Description	Number of minutes subjects were admitted to PACU following the surgical procedure
Time Frame	Time of discharge, approximately 1-2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Mean (Standard Deviation) [minutes]	65.2 (33.6)	75.0 (39.3)

3. Secondary Outcome

Title	Hospital Length of Stay
Description	Number days subjects were admitted to the hospital following the surgical procedure
Time Frame	Time of discharge, approximately 1-2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Mean (Standard Deviation) [days]	1.5 (0.9)	1.4 (0.8)

4. Secondary Outcome

Title	Maximum Pain Score
Description	Measured on a scale from 1 to 10 in the first 24 hours following the surgical procedure, 1=mild pain; 10=worst pain.
Time Frame	24 hours following the surgical procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Mean (Standard Deviation) [score on a scale]	6.0 (2.5)	6.5 (2.1)

5. Secondary Outcome

Title	Median Pain Score
Description	Measured on a scale from 1 to 10 in the first 24 hours following the surgical procedure, 1=mild pain; 10=worst pain.
Time Frame	24 hours following the surgical procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Mean (Standard Deviation) [score on a scale]	3.4 (1.9)	3.4 (1.6)

6. Secondary Outcome

Title	Discharge Pain Score
Description	Measured on a scale from 1 to 10 at time of hospital discharge, 1=mild pain; 10=worst pain.
Time Frame	Time of discharge, approximately 1-2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Mean (Standard Deviation) [score on a scale]	3.5 (2.1)	3.5 (2.1)

7. Secondary Outcome

Title	Orthostatic Hypotension
Description	Number of participants to experience orthostatic hypotension following the surgical procedure.
Time Frame	Time of discharge, approximately 1-2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Count of Participants [Participants]	4 5%	6 8.1%

8. Secondary Outcome

Title	Urinary Retention
Description	Number of participants to experience urinary retention follow the surgical procedure.
Time Frame	Time of discharge, approximately 1-2 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Count of Participants [Participants]	10 12.5%	10 13.5%

9. Secondary Outcome

Title	Transient Neurologic Symptoms
Description	Number of participants to report transient neurologic symptoms
Time Frame	One week post-operative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low-Dose Bupivacaine	Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic	Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
Measure Participants	80	74
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were collected from baseline to end of study for a total of approximately 6-9 days on all participants.
Arm/Group Title	Low-Dose Bupivacaine		Mepivacaine
Arm/Group Description	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. Low-Dose Bupivacaine: 10 mg (2 mL of 0.5%) administered as an isobaric spinal anesthetic		Subjects in this group will be given 70mg of Mepivacaine, which is within standard of care for spinal anesthesia during TKA or THA. Mepivacaine: 70 mg (3.5 mL of 2%) administered as an isobaric spinal anesthetic
All Cause Mortality
	Low-Dose Bupivacaine		Mepivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/74 (0%)
Serious Adverse Events
	Low-Dose Bupivacaine		Mepivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Low-Dose Bupivacaine		Mepivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/74 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.