Ignite Creation Date:
2024-05-06 @ 4:46 PM
Last Modification Date:
2024-10-26 @ 2:15 PM
Study NCT ID:
NCT05082155
Status:
WITHDRAWN
Last Update Posted:
2022-05-31
First Post:
2021-10-02
Brief Title:
Continuous Erector Spinae Plane Blocks to Treat Postoperative Pain After Open Gynecologic Procedures Via a Low Transverse Pfannenstiel Incision
Sponsor:
University of California San Diego
Organization:
University of California San Diego
Study Overview
Official Title:
Continuous Erector Spinae Plane Blocks to Treat Postoperative Pain After Open Gynecologic Procedures Via a Low Transverse Pfannenstiel Incision A Randomized Triple-masked Placebo-controlled Split-body Clinical Trial
Status:
WITHDRAWN
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
surgeons stopped doing procedures
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Open gynecologic surgery can be very painful With the goal of minimizing the use of opioids with undesired side effects and potential for abuse the investigators often administer a type of peripheral nerve block in which the investigators put local anesthetic-or numbing medicine-near the nerves that go to the surgical area which helps to numb the area and decrease pain following surgery These blocks with a single-injection of local anesthetic are called erector spinae plane ESP blocks and they are applied on each side of the body since each injection affects only that one side However the numbing medication typically lasts for only 16-20 hours For other peripheral nerve blocks this duration can be increased with the insertion of a catheter-a tiny tube smaller than a piece of spaghetti-followed by an infusion of additional local anesthetic However the effects of the various peripheral nerve blocks are determined by the anatomy and physiology of the specific peripheral nerve with an infusion resulting in dramatic benefits for one nerve yet having no effect for another The potential benefits and risks of adding a catheter and subsequent local anesthetic infusion to a single-injection ESP block remain unknown The investigatorstherefore propose a randomized triple-masked placebo-controlled split-body clinical trial to determine the potential benefits and risks of adding the infusion to single-injection ESP blocks
Detailed Description:
Open gynecologic surgery can be significantly painful With the goal of minimizing the use of opioids with undesired side effects and potential for abuse the investigators frequently administer bilateral single-injection erector spinae plane ESP blocks which help to numb the surgical area and decrease postoperative pain However the numbing medication typically lasts for only 8-18 hours For other peripheral nerve blocks this duration can be increased with the insertion of a percutaneous catheter-a tiny tube smaller than a piece of spaghetti-followed by an infusion of additional local anesthetic However the effects of the various peripheral nerve blocks are determined by the anatomy and physiology of the specific peripheral nerve with an infusion resulting in dramatic benefits for one nerve yet having no effect for another The potential benefits and risks of adding a catheter and subsequent local anesthetic infusion to a single-injection ESP block remain unknown
The investigators therefore propose a randomized triple-masked placebo-controlled split-body clinical trial to determine the potential benefits and risks of adding the infusion to single-injection ESP blocks Patients undergoing gynecologic surgery via a low transverse Pfannenstiel incision who already have bilateral ESP blocks as part of their analgesic plan will be offered enrollment Participants will have bilateral catheters inserted through the same block needles used for their single-injections followed by perineural administration of bupivacaine on one side and normal saline on the other determined randomly and in a triple-masked fashion
This will be a single-center randomized triple-masked placebo-controlled split-body human subjects clinical trial
Enrollment Participants will be consenting adults undergoing open gynecologic surgery via a low transverse incision Study inclusion will be proposed to eligible patients prior to surgery If a patient desires study participation written informed consent will be obtained using a current Institutional Review Board-approved informed consent form The study population of interest includes women of all races and socioeconomic status Inclusion and exclusion criteria are listed in section 10 below Of note the investigators will be using local anesthetic perineural catheters and infusion pumps as approvedcleared by the Food and Drug Administration and do not plan to research a possible change of indication or use of these medicationsdevices as part of this research project
Preoperative Procedures Following written informed consent the investigators will record baseline anthropometric information age sex height and weight that is already provided by all patients having surgery Participants will have a peripheral intravenous catheter inserted standard noninvasive monitors applied supplemental oxygen administered via a nasal cannula or face mask and positioned sitting Intravenous midazolam and fentanyl will be titrated for patient comfort while ensuring that patients remain responsive to verbal cues The area of insertion will be sterily prepared and a clear sterile fenestrated drape applied In the sitting position and with ultrasound guidance after subcutaneous local infiltration with lidocaine- a 17g Tuohy and 5-10 ml of saline with 1200000 epinephrine will be used to identify the correct plane as defined by a hyperechoic shadow of the 10th transverse process and erector spine muscle immediately superficial Once appropriate needle tip location is confirmed a perineural catheter will be inserted under ultrasound guidance This procedure will be repeated on the contralateral side
Following negative aspiration 20 mL of 025 bupivacaine with 1200000 of epinephrine will be injected via both catheters with sonographic confirmation of local anesthetic spread Blocks will be considered successful if within 30 minutes the participant experiences decreased sensation to cold temperature over the level of the ipsilateral 10th thoracic dermatome at the level of anterior axillary line Failed blockscatheters will be successfully replaced or the participant withdrawn from the study
Treatment Group Assignment The right-sided catheter will be randomized to one of two treatment groups bupivacaine 025 or normal saline study infusate The contralateral side will receive the other possible study infusate either bupivacaine 025 or normal saline Therefore each participant will receive both treatments-one on each side-and act as their own control
Randomization will be stratified for benign vs malignant surgical indication in block sizes of 4 The randomization list will be created by the University of California San Diego Investigational Drug Service Investigational pharmacists will prepare all study solutions as determined by the randomization list Bupivacaine and normal saline are indistinguishable in appearance and therefore investigators participants and all clinical staff will be masked to treatment group assignment for the duration of the enrollment and data collection period Unmasking will not occur until statistical analysis is complete termed triple masking
Study intervention Perineural study infusate administration will be initiated within the operating or recovery rooms Both infusion pumps will be programmed to deliver a basal infusion of 1 mLh and an automatic intermittent bolus of 20 mL every 4 hours This dose of bupivacaine is well-within the standard maximum dose at our institution for perineural local anesthetic administration for other truncal locations such as the paravertebral space No patient-controlled bolus dose will be included For any cases of inadvertent premature catheter dislodgement the subject may opt to have the catheter replaced
Perineural catheters will be removed by healthcare providers upon study infusate reservoir exhaustion approximately 50 hours or just prior to hospital discharge-whichever comes first
Postoperative analgesics In addition to the perineural study infusate subjects will receive standard-of-care oral and intravenous postoperative analgesics which can include acetaminophen ibuprofen gabapentin and opioids this is surgeon- and patient-dependent Therefore all patients of this study-regardless of the treatment arm they are randomized to-will continue to receive current usual and customary analgesia all will receive the same combination of acetaminophen ibuprofen gabapentin opioids and a single-injection erector spinae plane block as they would regardless of study participation
Outcome measurements end points The investigators have selected outcome measures that have established reliability and validity with minimal inter-rater discordance and are recommended for pain-related clinical trials by the World Health Organization and the Initiative on Methods Measurement and Pain Assessment in Clinical Trials IMMPACT consensus statement All data collection will be through standard UCSD nursingtherapy EPIC notes and patient interviews in-person during hospitalization or via a telephone call All pain scores will be recorded for each side of the body trunk at each time point measured using the Numeric Rating Scale
The overall objective of the proposed research is to determine the risks and benefits of adding a continuous erector spinae plane ESP block to a single-injection ESP in patients undergoing open gynecologic surgery via a low transverse incision
Specific Aim 1 To determine the risks and benefits of adding a continuous ESP block to a single-injection ESP the day following open gynecologic surgery
Hypothesis 11 Analgesia will be improved the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale average pain included in the Brief Pain Inventory pain domain primary end point
Hypothesis 12 Breakthrough pain will be decreased the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale worst pain included in the Brief Pain Inventory pain domain
Hypothesis 13 Pain during coughing will be decreased the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale
Specific Aim 2 To determine the risks and benefits on postoperative day 2 of adding a continuous ESP block to a single-injection ESP following open gynecologic surgery
Hypothesis 21 Analgesia will be improved on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale average pain included in the Brief Pain Inventory pain domain
Hypothesis 22 Breakthrough pain will be decreased on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale worst pain included in the Brief Pain Inventory pain domain
Hypothesis 23 Pain during coughing will be decreased on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale
Analysis Approach Baseline characteristics by randomized side bupivacaine to the left vs bupivacaine to the right will be summarized with means standard deviations and quartiles Balance between groups will be assessed Specifically standardized differences will be calculated using Cohens d whereby the difference in means or proportions is divided by the pooled standard deviation estimates Any key variables age sex height weight and BMI with an absolute standardized difference 078 with 1962125078 with a sample size of 25 the investigators expect about 125 randomized to left vs right will be noted and included in a linear regression model to obtain an estimate of the treatment effect adjusted for the imbalanced covariates If residuals from the linear regression indicate violations of key assumptions ie homoscedasticity or Gaussian distribution data transformations andor alternative generalized linear models will be applied as appropriate If no imbalance is detected the primary analysis will proceed by a one-sample Wilcoxon test applied to the difference between paired observations bupivacaine minus saline Secondary outcomes will also be analyzed by one-sample Wilcoxon test or linear models or generalized linear models as appropriate to adjust for any imbalanced covariates
The primary analysis will exclude patients from the analysis if their low transverse incision is unexpectedly converted to a vertical incision following randomization The investigators will compare the characteristics of these excluded participants compared to the primary analysis population and also report results for the full intention-to-treat population all randomized participants
Gatekeeping strategy Hypotheses will be tested with strong control of the familywise error rate at 5
Testing begins with a single primary hypotheses H11 If this test is significant at the 005 level that alpha is passed on to other hypotheses For example if the p-value for H12 is less than 0025 but the p-value for H13 is not then H13 can be tested at the 0025 00252 00375 level If both H12 and H13 are rejected no alpha is spent and the investigators go on to similarly test H21 H22 and H23 If a given test does not reach local significance alpha is spent and cannot be passed along to hypotheses
Simulated Power for NRS Power is estimated by simulations assuming a minimum clinically meaningful effect NRS difference scores bupivacaine minus saline with negative scores favoring bupivacaine are distributed with a median of -1 and interquartile range IQR -3 to 0 This IQR for a bilateral difference is consistent with unilateral IQRs 6 to 6 and 7 to 7 reported in Boules et al 2020 A sample size of n25 individuals would provide 84 power to detect such an effect with two-sided α005
Along with cancelled surgeries and drop-out cases the investigators anticipate requiring the consenting of 35 subjects to produce a data set consisting of a minimum of 25 subjects to be included in the final analysis
The investigators therefore propose a randomized triple-masked placebo-controlled split-body clinical trial to determine the potential benefits and risks of adding the infusion to single-injection ESP blocks Patients undergoing gynecologic surgery via a low transverse Pfannenstiel incision who already have bilateral ESP blocks as part of their analgesic plan will be offered enrollment Participants will have bilateral catheters inserted through the same block needles used for their single-injections followed by perineural administration of bupivacaine on one side and normal saline on the other determined randomly and in a triple-masked fashion
This will be a single-center randomized triple-masked placebo-controlled split-body human subjects clinical trial
Enrollment Participants will be consenting adults undergoing open gynecologic surgery via a low transverse incision Study inclusion will be proposed to eligible patients prior to surgery If a patient desires study participation written informed consent will be obtained using a current Institutional Review Board-approved informed consent form The study population of interest includes women of all races and socioeconomic status Inclusion and exclusion criteria are listed in section 10 below Of note the investigators will be using local anesthetic perineural catheters and infusion pumps as approvedcleared by the Food and Drug Administration and do not plan to research a possible change of indication or use of these medicationsdevices as part of this research project
Preoperative Procedures Following written informed consent the investigators will record baseline anthropometric information age sex height and weight that is already provided by all patients having surgery Participants will have a peripheral intravenous catheter inserted standard noninvasive monitors applied supplemental oxygen administered via a nasal cannula or face mask and positioned sitting Intravenous midazolam and fentanyl will be titrated for patient comfort while ensuring that patients remain responsive to verbal cues The area of insertion will be sterily prepared and a clear sterile fenestrated drape applied In the sitting position and with ultrasound guidance after subcutaneous local infiltration with lidocaine- a 17g Tuohy and 5-10 ml of saline with 1200000 epinephrine will be used to identify the correct plane as defined by a hyperechoic shadow of the 10th transverse process and erector spine muscle immediately superficial Once appropriate needle tip location is confirmed a perineural catheter will be inserted under ultrasound guidance This procedure will be repeated on the contralateral side
Following negative aspiration 20 mL of 025 bupivacaine with 1200000 of epinephrine will be injected via both catheters with sonographic confirmation of local anesthetic spread Blocks will be considered successful if within 30 minutes the participant experiences decreased sensation to cold temperature over the level of the ipsilateral 10th thoracic dermatome at the level of anterior axillary line Failed blockscatheters will be successfully replaced or the participant withdrawn from the study
Treatment Group Assignment The right-sided catheter will be randomized to one of two treatment groups bupivacaine 025 or normal saline study infusate The contralateral side will receive the other possible study infusate either bupivacaine 025 or normal saline Therefore each participant will receive both treatments-one on each side-and act as their own control
Randomization will be stratified for benign vs malignant surgical indication in block sizes of 4 The randomization list will be created by the University of California San Diego Investigational Drug Service Investigational pharmacists will prepare all study solutions as determined by the randomization list Bupivacaine and normal saline are indistinguishable in appearance and therefore investigators participants and all clinical staff will be masked to treatment group assignment for the duration of the enrollment and data collection period Unmasking will not occur until statistical analysis is complete termed triple masking
Study intervention Perineural study infusate administration will be initiated within the operating or recovery rooms Both infusion pumps will be programmed to deliver a basal infusion of 1 mLh and an automatic intermittent bolus of 20 mL every 4 hours This dose of bupivacaine is well-within the standard maximum dose at our institution for perineural local anesthetic administration for other truncal locations such as the paravertebral space No patient-controlled bolus dose will be included For any cases of inadvertent premature catheter dislodgement the subject may opt to have the catheter replaced
Perineural catheters will be removed by healthcare providers upon study infusate reservoir exhaustion approximately 50 hours or just prior to hospital discharge-whichever comes first
Postoperative analgesics In addition to the perineural study infusate subjects will receive standard-of-care oral and intravenous postoperative analgesics which can include acetaminophen ibuprofen gabapentin and opioids this is surgeon- and patient-dependent Therefore all patients of this study-regardless of the treatment arm they are randomized to-will continue to receive current usual and customary analgesia all will receive the same combination of acetaminophen ibuprofen gabapentin opioids and a single-injection erector spinae plane block as they would regardless of study participation
Outcome measurements end points The investigators have selected outcome measures that have established reliability and validity with minimal inter-rater discordance and are recommended for pain-related clinical trials by the World Health Organization and the Initiative on Methods Measurement and Pain Assessment in Clinical Trials IMMPACT consensus statement All data collection will be through standard UCSD nursingtherapy EPIC notes and patient interviews in-person during hospitalization or via a telephone call All pain scores will be recorded for each side of the body trunk at each time point measured using the Numeric Rating Scale
The overall objective of the proposed research is to determine the risks and benefits of adding a continuous erector spinae plane ESP block to a single-injection ESP in patients undergoing open gynecologic surgery via a low transverse incision
Specific Aim 1 To determine the risks and benefits of adding a continuous ESP block to a single-injection ESP the day following open gynecologic surgery
Hypothesis 11 Analgesia will be improved the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale average pain included in the Brief Pain Inventory pain domain primary end point
Hypothesis 12 Breakthrough pain will be decreased the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale worst pain included in the Brief Pain Inventory pain domain
Hypothesis 13 Pain during coughing will be decreased the day following surgery with the addition of a continuous ESP block as measured with the Numeric Rating Scale
Specific Aim 2 To determine the risks and benefits on postoperative day 2 of adding a continuous ESP block to a single-injection ESP following open gynecologic surgery
Hypothesis 21 Analgesia will be improved on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale average pain included in the Brief Pain Inventory pain domain
Hypothesis 22 Breakthrough pain will be decreased on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale worst pain included in the Brief Pain Inventory pain domain
Hypothesis 23 Pain during coughing will be decreased on postoperative day 2 with the addition of a continuous ESP block as measured with the Numeric Rating Scale
Analysis Approach Baseline characteristics by randomized side bupivacaine to the left vs bupivacaine to the right will be summarized with means standard deviations and quartiles Balance between groups will be assessed Specifically standardized differences will be calculated using Cohens d whereby the difference in means or proportions is divided by the pooled standard deviation estimates Any key variables age sex height weight and BMI with an absolute standardized difference 078 with 1962125078 with a sample size of 25 the investigators expect about 125 randomized to left vs right will be noted and included in a linear regression model to obtain an estimate of the treatment effect adjusted for the imbalanced covariates If residuals from the linear regression indicate violations of key assumptions ie homoscedasticity or Gaussian distribution data transformations andor alternative generalized linear models will be applied as appropriate If no imbalance is detected the primary analysis will proceed by a one-sample Wilcoxon test applied to the difference between paired observations bupivacaine minus saline Secondary outcomes will also be analyzed by one-sample Wilcoxon test or linear models or generalized linear models as appropriate to adjust for any imbalanced covariates
The primary analysis will exclude patients from the analysis if their low transverse incision is unexpectedly converted to a vertical incision following randomization The investigators will compare the characteristics of these excluded participants compared to the primary analysis population and also report results for the full intention-to-treat population all randomized participants
Gatekeeping strategy Hypotheses will be tested with strong control of the familywise error rate at 5
Testing begins with a single primary hypotheses H11 If this test is significant at the 005 level that alpha is passed on to other hypotheses For example if the p-value for H12 is less than 0025 but the p-value for H13 is not then H13 can be tested at the 0025 00252 00375 level If both H12 and H13 are rejected no alpha is spent and the investigators go on to similarly test H21 H22 and H23 If a given test does not reach local significance alpha is spent and cannot be passed along to hypotheses
Simulated Power for NRS Power is estimated by simulations assuming a minimum clinically meaningful effect NRS difference scores bupivacaine minus saline with negative scores favoring bupivacaine are distributed with a median of -1 and interquartile range IQR -3 to 0 This IQR for a bilateral difference is consistent with unilateral IQRs 6 to 6 and 7 to 7 reported in Boules et al 2020 A sample size of n25 individuals would provide 84 power to detect such an effect with two-sided α005
Along with cancelled surgeries and drop-out cases the investigators anticipate requiring the consenting of 35 subjects to produce a data set consisting of a minimum of 25 subjects to be included in the final analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None