Ignite Creation Date:
2024-05-06 @ 3:48 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04762381
Status:
COMPLETED
Last Update Posted:
2024-06-04
First Post:
2021-02-18
Brief Title:
Dexamethasone and Robotic-assisted Hysterectomy
Sponsor:
Herning Hospital
Organization:
Herning Hospital
Study Overview
Official Title:
Effect of 24 mg Dexamethasone Preoperatively on Surgical Stress Pain and Recovery in Robotic-assisted Laparoscopic Hysterectomy
Status:
COMPLETED
Status Verified Date:
2024-05
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:
Robotic-assisted hysterectomy is an alternative to laparoscopic surgery as part of a minimal invasive regimen Several treatment strategies are followed to improve the overall outcome and minimize surgical stress Glucocorticoids provide significant analgesic and antiemetic effects but its role in a fast-track multi-modal setting is not settled when discharge is planned within 24-36 hours
This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on women undergoing robotic-assisted hysterectomy with regard to surgical stress measured by c-reactive protein as primary outcome and further other stress markers like white blood cells The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use quality of recovery incontinence sexual and work life Furthermore in a sub-analysis transcriptional profiling will be applied to explore which parts of the innate and cellular immune system is activated to explore the mechanisms of surgical stress response
The hypothesis is that women undergoing robotic hysterectomy would benefit from peroperative glucocorticoid treatment on important life qualities like pain fatigue freedom of medications and resuming work and sexual activities Further future adjuvant peroperative regimens may be able to target the stress response in a more appropriate way
This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on women undergoing robotic-assisted hysterectomy with regard to surgical stress measured by c-reactive protein as primary outcome and further other stress markers like white blood cells The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use quality of recovery incontinence sexual and work life Furthermore in a sub-analysis transcriptional profiling will be applied to explore which parts of the innate and cellular immune system is activated to explore the mechanisms of surgical stress response
The hypothesis is that women undergoing robotic hysterectomy would benefit from peroperative glucocorticoid treatment on important life qualities like pain fatigue freedom of medications and resuming work and sexual activities Further future adjuvant peroperative regimens may be able to target the stress response in a more appropriate way
Detailed Description:
Background Robotic operations in gynecology is one of the fastest growing fields in applied robotic technology
In Denmark 4000 hysterectomies are performed each year on benign indications and minimal invasive techniques has risen from 35 to 80 These operations consist of vaginal laparoscopic assisted und the latest robotic assisted hysterectomy Hysterectomy and prostate operations are the most common robotic assisted operations as an alternative to conventional laparoscopy
Robotic surgery on benign indications in gynecology is still a discussion on the cost vs benefit due to increased cost and lack of evidence on superiority in surgical outcome compared to conventional laparoscopy For minimal invasive surgery is but a part of a complex series of treatment in a strategy the so-called multi-modal regimen 1-716 By this the day of discharge has dramatically decreased without compromising safety during surgery and postoperative recovery However not all single elements are proven for efficacy let alone the specific targets for effect 16
To further improve the overall outcome of surgery the surgical stress response are investigated which includes inflammatory components and are of importance of postoperative pain and recovery 8916 Here amongst others glucocorticoids have proven to relieve pain in a number of procedures applied in general surgery on colon gallbladder and breast in orthopedic surgery on knee and breast surgery and in gynecology too in laparoscopic hysterectomy 1-101516 The dose of steroid to provide significant analgesic effect is at least dexamethasone of 01-02 mgkg or 15 mg which is substantiated in some reduction in inflammatory response 71516 Glucocorticoids are known for analgesic opioid-sparing and antiemetic effects but procedure-specific outcome are lacking Similarly the specific anti-inflammatory and sites of surgical stress-related responses are not well elucidated
Aim The PhD study evaluate the effects of a single dose of steroid on acute postoperative stress response and pain after hysterectomy The evaluation is on clinical relevant outcome that directly benefit the patients We will measure surgical stress by c-reactive protein and other inflammatory markers based on transcriptional profiling register pain and medication needed during hospital stay and after discharge and when work and sexual function could be resumed
Outcome The primary endpoint is reduction of postoperative c-reactive protein crp after robotic hysterectomy as an objective measurement of the stress amelioration by the given steroid The rise postoperatively will be ascertained by two baseline measurements and every 4-6 hours after operation as long as the women is not discharged The crp is not expected to be dependent on each operation team eagerness to perform well or the postoperative care to reach certain standards
As secondary outcome we register pain scores from baseline to 24 h and later on the postoperative analgesics medication from baseline to discharge and later on quality of recovery QoR-15D in the latest 24 hours 12 Further after discharge incontinence ICIQ-UI start of sexual life PISQ-1231 inflammatory markers and resumption to recreational and work life will be ascertained in a diary The baseline and early acute postoperative pain scores visual analog scale VAS at rest and at movement 0-4 h postoperatively late acute postoperative pain scores VAS at rest and at movement 24 h postoperatively and cumulative opioid consumption up to 24 h will be registered Part of blood samples will be stored for analysis of the cellular inflammatory systems by NanoString to explore the innate system and cellular activation 1920 NanoString has the capacity to demonstrate activation of immune-related genes in the bloodstream during inflammatory induction and highlight an exciting role of immune competent cell in linking peripheral inflammation with immune activation and possibly anti-nociception NanoString methodology investigates gene expression and currently quantifies the expression of 770 genes by determining the amount of messenger RNA mRNA mRNA is the end-product of gene transcription and therefore allows the study of gene up-regulation
Monitoring cycles and levels of rest and activity will be done by an actigraph in a non-invasive method 1314
Hypothesis Women undergoing robotic hysterectomy would benefit from peroperative glucocorticoid treatment on important life qualities like pain fatigue freedom of medications and resuming work and sexual activities Biological substrates such as inflammatory markers will be explored as underlying mechanism behind surgical stress response in order to direct perioperative medical interventions 19
Perspectives and impact The randomized design will evaluate the effects of the single dose dexamethasone on the highest level of evidence The anti-emetic effects of steroid are already incorporated in several guidelines on perioperative care however this study could further enhance our knowledge on minimal invasive surgery and optimize the treatment for surgical stress The stress response in humans have evolved over millennia and is embedded in our genes but has no natural association with modern days surgery and may be ill placed and timely inadequate for recovery The exploratory study may help identify pathways and specific mechanism in surgical stress that can be targeted in future to enhance womens recovery after surgery The perspective is in further studies to target these specific sites in the immune activation
Methods
The PhD study in robotic hysterectomy will include a randomized trial with a single dose intravenously of 24 mg dexamethasone Dexavit corresponding to 128 mg methyl prednisolone Solumedrol
The randomization will be performed in Redcap and data stored the same place under each patient cpr-no but in a separate section A person not involved in the project in any other form will perform the randomization The patient will then receive the dose of either steroid or placebo saline intravenously blinded to the patient and operation team gynecology operation ward and anesthesiology The applicant PhD student will later enter the data in Redcap unknowing to the randomization results
All women in the department operated by with a robotic assisted hysterectomy will be monitored and fill out a diary with validated questionnaires names of quest to streamline the information gathering in a high flow work place and not to discriminate those outside of the project These data will be presented as the drop-out analysis to evaluate the external validity of the trial The flow of data collection is displayed below
Sample size was calculated to be 49 women included in each arm on the primary outcome of c-reactive protein rising to the level of 40 mgl with an expected reduction of 10 a with a standard deviation of 7 calculated by httpsclincalccomstatssamplesizeaspx 11718 This may seem a parsimonious reduction but in practical terms it translates to more than halving the need of opioids early and late postoperatively 2 On the assumption of incomplete data in less than 10 of cases 50 women in each group with complete data will be included Robotic hysterectomy is a standard procedure in our department with about 80-90 hysterectomies each year so we expect the study inclusion to last 1½-2 years
Statistics Analysis are performed on the intention-to-treat principle with women on current use of analgesics as a subgroup analysis The statistics will be unpaired and paired analysis 2-ways ANOVA including relevant co-variates Regression analysis will be performed with the primary outcome as dependent variable and the secondary outcomes and anthropometrics as dependent variable
In Denmark 4000 hysterectomies are performed each year on benign indications and minimal invasive techniques has risen from 35 to 80 These operations consist of vaginal laparoscopic assisted und the latest robotic assisted hysterectomy Hysterectomy and prostate operations are the most common robotic assisted operations as an alternative to conventional laparoscopy
Robotic surgery on benign indications in gynecology is still a discussion on the cost vs benefit due to increased cost and lack of evidence on superiority in surgical outcome compared to conventional laparoscopy For minimal invasive surgery is but a part of a complex series of treatment in a strategy the so-called multi-modal regimen 1-716 By this the day of discharge has dramatically decreased without compromising safety during surgery and postoperative recovery However not all single elements are proven for efficacy let alone the specific targets for effect 16
To further improve the overall outcome of surgery the surgical stress response are investigated which includes inflammatory components and are of importance of postoperative pain and recovery 8916 Here amongst others glucocorticoids have proven to relieve pain in a number of procedures applied in general surgery on colon gallbladder and breast in orthopedic surgery on knee and breast surgery and in gynecology too in laparoscopic hysterectomy 1-101516 The dose of steroid to provide significant analgesic effect is at least dexamethasone of 01-02 mgkg or 15 mg which is substantiated in some reduction in inflammatory response 71516 Glucocorticoids are known for analgesic opioid-sparing and antiemetic effects but procedure-specific outcome are lacking Similarly the specific anti-inflammatory and sites of surgical stress-related responses are not well elucidated
Aim The PhD study evaluate the effects of a single dose of steroid on acute postoperative stress response and pain after hysterectomy The evaluation is on clinical relevant outcome that directly benefit the patients We will measure surgical stress by c-reactive protein and other inflammatory markers based on transcriptional profiling register pain and medication needed during hospital stay and after discharge and when work and sexual function could be resumed
Outcome The primary endpoint is reduction of postoperative c-reactive protein crp after robotic hysterectomy as an objective measurement of the stress amelioration by the given steroid The rise postoperatively will be ascertained by two baseline measurements and every 4-6 hours after operation as long as the women is not discharged The crp is not expected to be dependent on each operation team eagerness to perform well or the postoperative care to reach certain standards
As secondary outcome we register pain scores from baseline to 24 h and later on the postoperative analgesics medication from baseline to discharge and later on quality of recovery QoR-15D in the latest 24 hours 12 Further after discharge incontinence ICIQ-UI start of sexual life PISQ-1231 inflammatory markers and resumption to recreational and work life will be ascertained in a diary The baseline and early acute postoperative pain scores visual analog scale VAS at rest and at movement 0-4 h postoperatively late acute postoperative pain scores VAS at rest and at movement 24 h postoperatively and cumulative opioid consumption up to 24 h will be registered Part of blood samples will be stored for analysis of the cellular inflammatory systems by NanoString to explore the innate system and cellular activation 1920 NanoString has the capacity to demonstrate activation of immune-related genes in the bloodstream during inflammatory induction and highlight an exciting role of immune competent cell in linking peripheral inflammation with immune activation and possibly anti-nociception NanoString methodology investigates gene expression and currently quantifies the expression of 770 genes by determining the amount of messenger RNA mRNA mRNA is the end-product of gene transcription and therefore allows the study of gene up-regulation
Monitoring cycles and levels of rest and activity will be done by an actigraph in a non-invasive method 1314
Hypothesis Women undergoing robotic hysterectomy would benefit from peroperative glucocorticoid treatment on important life qualities like pain fatigue freedom of medications and resuming work and sexual activities Biological substrates such as inflammatory markers will be explored as underlying mechanism behind surgical stress response in order to direct perioperative medical interventions 19
Perspectives and impact The randomized design will evaluate the effects of the single dose dexamethasone on the highest level of evidence The anti-emetic effects of steroid are already incorporated in several guidelines on perioperative care however this study could further enhance our knowledge on minimal invasive surgery and optimize the treatment for surgical stress The stress response in humans have evolved over millennia and is embedded in our genes but has no natural association with modern days surgery and may be ill placed and timely inadequate for recovery The exploratory study may help identify pathways and specific mechanism in surgical stress that can be targeted in future to enhance womens recovery after surgery The perspective is in further studies to target these specific sites in the immune activation
Methods
The PhD study in robotic hysterectomy will include a randomized trial with a single dose intravenously of 24 mg dexamethasone Dexavit corresponding to 128 mg methyl prednisolone Solumedrol
The randomization will be performed in Redcap and data stored the same place under each patient cpr-no but in a separate section A person not involved in the project in any other form will perform the randomization The patient will then receive the dose of either steroid or placebo saline intravenously blinded to the patient and operation team gynecology operation ward and anesthesiology The applicant PhD student will later enter the data in Redcap unknowing to the randomization results
All women in the department operated by with a robotic assisted hysterectomy will be monitored and fill out a diary with validated questionnaires names of quest to streamline the information gathering in a high flow work place and not to discriminate those outside of the project These data will be presented as the drop-out analysis to evaluate the external validity of the trial The flow of data collection is displayed below
Sample size was calculated to be 49 women included in each arm on the primary outcome of c-reactive protein rising to the level of 40 mgl with an expected reduction of 10 a with a standard deviation of 7 calculated by httpsclincalccomstatssamplesizeaspx 11718 This may seem a parsimonious reduction but in practical terms it translates to more than halving the need of opioids early and late postoperatively 2 On the assumption of incomplete data in less than 10 of cases 50 women in each group with complete data will be included Robotic hysterectomy is a standard procedure in our department with about 80-90 hysterectomies each year so we expect the study inclusion to last 1½-2 years
Statistics Analysis are performed on the intention-to-treat principle with women on current use of analgesics as a subgroup analysis The statistics will be unpaired and paired analysis 2-ways ANOVA including relevant co-variates Regression analysis will be performed with the primary outcome as dependent variable and the secondary outcomes and anthropometrics as dependent variable
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None