Ignite Creation Date:
2024-05-06 @ 3:08 AM
Last Modification Date:
2024-10-26 @ 11:29 AM
Study NCT ID:
NCT02219438
Status:
COMPLETED
Last Update Posted:
2021-03-19
First Post:
2014-08-14
Brief Title:
Continuous Adductor Canal Nerve Blocks Relative Effects of a Basal Infusion v Hourly Bolus Doses
Sponsor:
University of California San Diego
Organization:
University of California San Diego
Study Overview
Official Title:
Continuous Adductor Canal Nerve Blocks Relative Effects of a Basal Infusion v Hourly Bolus Doses
Status:
COMPLETED
Status Verified Date:
2021-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients usually experience moderate-to-severe pain following the knee replacement that is often treated with a femoral nerve block injection of numbing medicine placed around the main nerve of the knee joint To make the nerve block last longer a tiny tube is often placed next to the nerve and numbing medicine is infused for multiple days However while the numbing medicine takes away pain it also decreases sensations muscle strength and proprioception knowing where the leg is in space without looking at it which greatly increases the risk of falling Since falling can be catastrophic following major surgery a femoral nerve blocks are being phased out by surgeons and anesthesiologists The most-promising replacement is called an adductor canal nerve block For this new type of block a perineural catheter is inserted into a small canal in the middle of the upper leg This canal contains the sensory nerve fibers leading to the knee and only a single nerve that serves a relatively small muscle Multiple studies have demonstrated a dramatic increase in muscle strength using the new adductor canal block compared with the traditional femoral block However practitioners perceptions of the new block is that it provides insufficient pain control following knee arthroplasty even though all of the sensory nerves affected with the femoral block are also-theoretically-affected with the adductor canal block One reason for this difference may be the small canal of the latter which is a relatively tight area in which the numbing medicine might not spread particularly well due to pressure from surrounding tissues One way to possibly counter this issue is by providing repeated boluses of the numbing medicine that will improve the medicines spread relative to a more-traditional slow continuous basal infusion This study seeks to compare these two techniques of medication administration through perineural adductor canal catheters
Our primary aim is to test the hypothesis that for continuous adductor canal blocks providing local anesthetic as repeated hourly bolus doses results in an increased sensory block compared with providing local anesthetic as a continuous basal infusion at an equivalent hourly dose
As a secondary aim we hypothesize that for continuous adductor canal blocks providing local anesthetic as repeated hourly bolus doses results in either equivalent or less motor block compared with providing local anesthetic as a continuous basal infusion at an equivalent hourly dose
Our primary aim is to test the hypothesis that for continuous adductor canal blocks providing local anesthetic as repeated hourly bolus doses results in an increased sensory block compared with providing local anesthetic as a continuous basal infusion at an equivalent hourly dose
As a secondary aim we hypothesize that for continuous adductor canal blocks providing local anesthetic as repeated hourly bolus doses results in either equivalent or less motor block compared with providing local anesthetic as a continuous basal infusion at an equivalent hourly dose
Detailed Description:
This investigation will be a randomized observer-masked controlled split-body human-subjects clinical trial Of note we will be using standard-of-care local anesthetics under their FDA approved purpose and do not plan to research a possible change of indication or use of these drugs as part of this research project
Enrollment Subjects will be volunteers of both sexes age 18 and older Volunteers will be solicited using newspaper advertisements fliers the CTRI Research Match and an existing database of volunteers IRB approved If a volunteer meets inclusionexclusion criteria and desires study participation written informed consent will be obtained Selection for inclusion will not be based on race or socioeconomic status The study population of interest includes men and women of all races and socioeconomic status A urine pregnancy test will be administered to all women of childbearing age following written informed consent but before any study interventions This urine test will be administered by CTRI nursing staff using standard FDA-approved urine pregnancy testing devices
Inclusion and Exclusion Criteria See section 10 below
Perineural catheter insertion Following written informed consent subjects will be admitted to the UCSD CTRI Center for Clinical Research Services CCR inpatient unit and have demographicmorphometric data recorded eg age weight height An intravenous line will be placed in an upper extremity followed by external monitors pulse oximeter blood pressure and EKG and oxygen by nasal cannula Sedation will be provided with intravenous fentanyl 50 μg andor midazolam 1 mg or oral valium 10 mg andor dilaudid 4 mg as necessary Subjects will then have bilateral adductor canal perineural catheters placed using standard UC San Diego techniques
Treatment Group Assignment Subjects will act as their own controls The dominant side left or right will be randomized to one of two treatment groups ropivacaine 02 administration as either a basal infusion 8 mLh or bolus doses 8 mL administered hourly The non-dominant contralateral side will receive the other possible treatment Randomization will be based on computer-generated codes Randomization will be in blocks of two and stratified by sex An infusion pump with study infusate will be attached to each of the perineural catheters and initiated at Hour 0 The basal rate and bolus volume will depend upon the treatment group note that the basal rate and bolus volume differ for each treatment group but the total dose of local anesthetic is the same for each
Treatment Group Basal Rate mLh Basal Dose mgh Bolus Volume mL Bolus Dose mg Total Dose mgh Basal Infusion 8 16 0 0 16 Bolus Doses 0 0 8 16 16
The tubing from the pumps to the subjects will be gently wound at least 5 rotations and covered with opaque tape masking which perineural catheter is receiving which treatment ropivacaine is clear so the flow through the clear tubing from the tape to the perineural catheters will not be visually distinguishable
Local Anesthetic Administration The infusion pump administering the basal infusion will be initiated at Hour 0 The infusion pump administering bolus doses will administer a 8 mL bolus dose each hour beginning at Hour 0 Perineural catheters will be removed after 8 hours
To check the perineural catheter placement accuracy the adductor canal nerve block will be evaluated 8 hours after local anesthetic initiation and considered successful when subjects experience a decreased sensation to cold of the skin in the saphenous nerve distribution as compared with their ipsilateral upper extremity Subjects will be deemed non-responders if both extremities failed to exhibit any increase in tolerance to cutaneous electrical current by Hour 8 For unsuccessful perineural catheter insertion non-responders or if a perineural catheter is inadvertently dislodged prior to the measurement of the primary endpoint the data will not be included in the analyses and the subject dropped from the study
Food and Drink Both food and accompanying beverageswater will be provided by the hospital and served by the nursing staff immediately following catheter insertion Meals will be provided without charge to the study subjects There is no restriction on oral intake following catheter insertion Subjects will remain within the CTRI-CCR until the following morning for the final measurement
Outcome Measurements We have selected measures that have established reliability and validity Staff blinded to treatment group assignment will perform all measures and assessments Measurements will be performed prior to local anesthetic administration initiation baseline Hour 0 as well as hourly following local anesthetic infusionbolus initiation through Hour 14 and one final measurement set prior to discharge the following morning at approximately Hour 22 see Table below For all measurements the dominant side will always be tested first followed by the contralateral side
Tolerance of transcutaneous electrical stimulation Evaluated in the seated position using transcutaneous electrical stimulation TES in the same manner as described throughout the anesthesia literature this is a gold standard for regional anesthesia studies EKG pads will be positioned over the proximal patella and quadriceps tendon 1 cm medial of midline and attached to a nerve stimulator The current will be increased from 0 mA until the subject reports slight discomfort or up to a maximum of 80 mA at which time the current is recorded as the TES value and the nerve stimulator turned off
Quadriceps femoris muscle strength Evaluated using a portable isometric force dynamometer to measure the maximum voluntary isometric contraction MVIC in a seated position The primary end point will be the quadriceps femoris maximum voluntary isometric contraction MVIC expressed as a percentage of the pre-ropivacaine baseline MVIC post pre x 100 with the two sides of each subject compared with each other at Hour 8
Statistical Analysis Plan We will assess the noninferiority of the bolus method hourly 8 mL ropivacaine 02 bolus doses compared to basal infusion ropivacaine 02 8 mLh continuous basal infusion on the primary endpoint of tolerance to cutaneous current at 8 hours using a 1-tailed t-test at the 0025 significance level with an a priori-specified noninferiority delta of 10 mA A value of 10 mA is determined a priori to be the smallest difference that would be clinically important between groups This value is considered the minimally clinically-relevant current since it approximates the tolerated electrical current range at baseline of the general population-in other words natural variability and therefore a relatively small amount of current to detect A positive test for noninferiority will be accompanied by the 95 confidence interval 0025 in the hypothesized direction for the difference in means not including the noninferiority delta
Secondary analysis will assess noninferiority of the bolus to the basal infusion method on mean tolerance to cutaneous current across all time points measured using a noninferiority delta of 10 mA as above In this repeated measures setting noninferiority will be assessed in the context of a linear mixed model adjusting for the within-subject correlation using an auto-regressive correlation structure If the time-by-group interaction is non-significant P020 we will assess noninferiority collapsing over time and constructing a 1-tailed t-test using noninferiority delta of 10 mA based on the model-based treatment effect for bolus versus basal infusion In presence of a group-time interaction noninferiority will be assessed separately at each time point and a Holm-Bonferroni correction made for multiple comparisons to maintain the hypothesis-wise type I error at 0025
We will also assess noninferiority of bolus to basal infusion on the secondary endpoint of quadriceps femoris MVIC 22 hours total using a mixed effects model as described above
The rejection region for a noninferiority test includes superiority by definition ie not worse implies either equivalent or better Therefore if bolus is found to not only be noninferior but also superior we will be able to claim superiority This will be evidenced by the 95 CI for the difference between means falling above zero
Although we hypothesize that the bolus method will be noninferior to basal infusion it is possible that basal infusion would be noninferior to bolus Therefore we will also conduct the above tests assessing noninferiority of basal infusion to bolus If noninferiority is found in both directions we will claim equivalence at 10mA SAS software 93 SAS Institute Cary NC USA and R software versions 2153 The R Foundation for Statistical Computing Vienna Austria will be used for all analyses
Sample Size Estimation Sample size calculations are based on the primary aim of determining the relationship between perineural ropivacaine delivery technique basal vs bolus and continuous adductor canal nerve block effects To this end we will perform a noninferiority trial with the primary endpoint designated as the maximum tolerance to transcutaneous electrical stimulation at Hour 8 With 24 subjects we will have approximately 90 power 88 at the 0025 significance level to detect noninferiority of bolus ropivacaine to basal infusion ropivacaine on mean tolerance to transcutaneous electrical stimulation at Hour 8 using an a priori noninferiority delta of 10 mA Based on previously-published data this conservatively assumes a standard deviation of tolerance difference between legs of 15 mA
We will apply the same analysis of percent change from baseline at Hour 0 to the secondary outcome measures We will also examine the time profiles of the responses over time with spaghetti and mean plots Further secondary analyses will include mixed-effects modeling of the repeated hourly measures to confirm the analysis of percent change at 8 hours These models will account for the hierarchical correlation of paired measures from each subject over time We will use these models to test the effects of subject characteristics including handedness sex height weight body mass index and age
Enrollment Subjects will be volunteers of both sexes age 18 and older Volunteers will be solicited using newspaper advertisements fliers the CTRI Research Match and an existing database of volunteers IRB approved If a volunteer meets inclusionexclusion criteria and desires study participation written informed consent will be obtained Selection for inclusion will not be based on race or socioeconomic status The study population of interest includes men and women of all races and socioeconomic status A urine pregnancy test will be administered to all women of childbearing age following written informed consent but before any study interventions This urine test will be administered by CTRI nursing staff using standard FDA-approved urine pregnancy testing devices
Inclusion and Exclusion Criteria See section 10 below
Perineural catheter insertion Following written informed consent subjects will be admitted to the UCSD CTRI Center for Clinical Research Services CCR inpatient unit and have demographicmorphometric data recorded eg age weight height An intravenous line will be placed in an upper extremity followed by external monitors pulse oximeter blood pressure and EKG and oxygen by nasal cannula Sedation will be provided with intravenous fentanyl 50 μg andor midazolam 1 mg or oral valium 10 mg andor dilaudid 4 mg as necessary Subjects will then have bilateral adductor canal perineural catheters placed using standard UC San Diego techniques
Treatment Group Assignment Subjects will act as their own controls The dominant side left or right will be randomized to one of two treatment groups ropivacaine 02 administration as either a basal infusion 8 mLh or bolus doses 8 mL administered hourly The non-dominant contralateral side will receive the other possible treatment Randomization will be based on computer-generated codes Randomization will be in blocks of two and stratified by sex An infusion pump with study infusate will be attached to each of the perineural catheters and initiated at Hour 0 The basal rate and bolus volume will depend upon the treatment group note that the basal rate and bolus volume differ for each treatment group but the total dose of local anesthetic is the same for each
Treatment Group Basal Rate mLh Basal Dose mgh Bolus Volume mL Bolus Dose mg Total Dose mgh Basal Infusion 8 16 0 0 16 Bolus Doses 0 0 8 16 16
The tubing from the pumps to the subjects will be gently wound at least 5 rotations and covered with opaque tape masking which perineural catheter is receiving which treatment ropivacaine is clear so the flow through the clear tubing from the tape to the perineural catheters will not be visually distinguishable
Local Anesthetic Administration The infusion pump administering the basal infusion will be initiated at Hour 0 The infusion pump administering bolus doses will administer a 8 mL bolus dose each hour beginning at Hour 0 Perineural catheters will be removed after 8 hours
To check the perineural catheter placement accuracy the adductor canal nerve block will be evaluated 8 hours after local anesthetic initiation and considered successful when subjects experience a decreased sensation to cold of the skin in the saphenous nerve distribution as compared with their ipsilateral upper extremity Subjects will be deemed non-responders if both extremities failed to exhibit any increase in tolerance to cutaneous electrical current by Hour 8 For unsuccessful perineural catheter insertion non-responders or if a perineural catheter is inadvertently dislodged prior to the measurement of the primary endpoint the data will not be included in the analyses and the subject dropped from the study
Food and Drink Both food and accompanying beverageswater will be provided by the hospital and served by the nursing staff immediately following catheter insertion Meals will be provided without charge to the study subjects There is no restriction on oral intake following catheter insertion Subjects will remain within the CTRI-CCR until the following morning for the final measurement
Outcome Measurements We have selected measures that have established reliability and validity Staff blinded to treatment group assignment will perform all measures and assessments Measurements will be performed prior to local anesthetic administration initiation baseline Hour 0 as well as hourly following local anesthetic infusionbolus initiation through Hour 14 and one final measurement set prior to discharge the following morning at approximately Hour 22 see Table below For all measurements the dominant side will always be tested first followed by the contralateral side
Tolerance of transcutaneous electrical stimulation Evaluated in the seated position using transcutaneous electrical stimulation TES in the same manner as described throughout the anesthesia literature this is a gold standard for regional anesthesia studies EKG pads will be positioned over the proximal patella and quadriceps tendon 1 cm medial of midline and attached to a nerve stimulator The current will be increased from 0 mA until the subject reports slight discomfort or up to a maximum of 80 mA at which time the current is recorded as the TES value and the nerve stimulator turned off
Quadriceps femoris muscle strength Evaluated using a portable isometric force dynamometer to measure the maximum voluntary isometric contraction MVIC in a seated position The primary end point will be the quadriceps femoris maximum voluntary isometric contraction MVIC expressed as a percentage of the pre-ropivacaine baseline MVIC post pre x 100 with the two sides of each subject compared with each other at Hour 8
Statistical Analysis Plan We will assess the noninferiority of the bolus method hourly 8 mL ropivacaine 02 bolus doses compared to basal infusion ropivacaine 02 8 mLh continuous basal infusion on the primary endpoint of tolerance to cutaneous current at 8 hours using a 1-tailed t-test at the 0025 significance level with an a priori-specified noninferiority delta of 10 mA A value of 10 mA is determined a priori to be the smallest difference that would be clinically important between groups This value is considered the minimally clinically-relevant current since it approximates the tolerated electrical current range at baseline of the general population-in other words natural variability and therefore a relatively small amount of current to detect A positive test for noninferiority will be accompanied by the 95 confidence interval 0025 in the hypothesized direction for the difference in means not including the noninferiority delta
Secondary analysis will assess noninferiority of the bolus to the basal infusion method on mean tolerance to cutaneous current across all time points measured using a noninferiority delta of 10 mA as above In this repeated measures setting noninferiority will be assessed in the context of a linear mixed model adjusting for the within-subject correlation using an auto-regressive correlation structure If the time-by-group interaction is non-significant P020 we will assess noninferiority collapsing over time and constructing a 1-tailed t-test using noninferiority delta of 10 mA based on the model-based treatment effect for bolus versus basal infusion In presence of a group-time interaction noninferiority will be assessed separately at each time point and a Holm-Bonferroni correction made for multiple comparisons to maintain the hypothesis-wise type I error at 0025
We will also assess noninferiority of bolus to basal infusion on the secondary endpoint of quadriceps femoris MVIC 22 hours total using a mixed effects model as described above
The rejection region for a noninferiority test includes superiority by definition ie not worse implies either equivalent or better Therefore if bolus is found to not only be noninferior but also superior we will be able to claim superiority This will be evidenced by the 95 CI for the difference between means falling above zero
Although we hypothesize that the bolus method will be noninferior to basal infusion it is possible that basal infusion would be noninferior to bolus Therefore we will also conduct the above tests assessing noninferiority of basal infusion to bolus If noninferiority is found in both directions we will claim equivalence at 10mA SAS software 93 SAS Institute Cary NC USA and R software versions 2153 The R Foundation for Statistical Computing Vienna Austria will be used for all analyses
Sample Size Estimation Sample size calculations are based on the primary aim of determining the relationship between perineural ropivacaine delivery technique basal vs bolus and continuous adductor canal nerve block effects To this end we will perform a noninferiority trial with the primary endpoint designated as the maximum tolerance to transcutaneous electrical stimulation at Hour 8 With 24 subjects we will have approximately 90 power 88 at the 0025 significance level to detect noninferiority of bolus ropivacaine to basal infusion ropivacaine on mean tolerance to transcutaneous electrical stimulation at Hour 8 using an a priori noninferiority delta of 10 mA Based on previously-published data this conservatively assumes a standard deviation of tolerance difference between legs of 15 mA
We will apply the same analysis of percent change from baseline at Hour 0 to the secondary outcome measures We will also examine the time profiles of the responses over time with spaghetti and mean plots Further secondary analyses will include mixed-effects modeling of the repeated hourly measures to confirm the analysis of percent change at 8 hours These models will account for the hierarchical correlation of paired measures from each subject over time We will use these models to test the effects of subject characteristics including handedness sex height weight body mass index and age
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None