Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06453447
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-11
First Post:
2024-06-05
Brief Title:
Prednisone for CRPS in Distal Radius Fracture
Sponsor:
University of British Columbia
Organization:
University of British Columbia
Study Overview
Official Title:
Prednisone for the Early Treatment of Complex Regional Pain Syndrome After Distal Radius Fracture - a Pilot Randomized Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
Wrist fractures are the most prevalent adult fracture Complex regional pain syndrome CRPS is a common complication that can occur leading to permanent disability and is costly to the patient and healthcare system In addition amidst the opioid epidemic the risk of increased opioid use in patients with CRPS prompts the need to find viable treatment strategies This study aims to evaluate an anti-inflammatory medication prednisone in the early treatment of CRPS Patients with wrist fractures who undergo surgical treatment will be randomized to receiving placebo vs prednisone for 2 weeks Clinical assessments in the follow up period will be compared
Detailed Description:
Purpose
Distal radius fractures are the most prevalent adult fracture accounting for 175 of all fractures Complex regional pain syndrome CRPS is a common complication that can occur in this population with a reported incidence of up to 32 CRPS can lead to permanent disability and is costly to the patient and to the healthcare system with an estimated cumulative outpatient and pain prescription cost of 42026 over 8 years after diagnosis In addition amidst the opioid epidemic the risk of increased opioid use in patients with CRPS prompts the need to find viable treatment strategies
While there have been various proposed treatment modalities evidence from randomized studies is lacking Several small studies retrospective and prospective case series have shown potential efficacy of glucocorticoids for the treatment of CRPS To our knowledge there are no randomized controlled trials that evaluate treatment of CRPS in distal radius fractures with glucocorticoids
The purpose of this pilot study is to evaluate a short course of oral prednisone as potential treatment for patients identified as developing early signs of CRPS after sustaining a distal radius fracture that was treated operatively We will examine feasibility metrics including patient recruitment rate adherence to allocation and protocol withdrawal from study and follow-through in order to inform design of a definitive clinical trial We will also assess the resolution of CRPS post-operative opioid use and any adverse events in patients who sustain a distal radius fracture after receiving prednisone vs placebo for 2 weeks post-operatively with 6 months follow up post injury
Hypothesis
We hypothesize that the proposed pilot trial will demonstrate feasibility of a future definitive trial
In addition we hypothesize that there will be higher rates of CRPS resolution lower amounts of opioid consumption and no increased adverse effects and better clinical outcomes in patients who receive prednisone treatment compared to those who received placebo However formal hypothesis testing will not be performed for this pilot trial
Justification
Developing CRPS after sustaining a distal radius fracture can lead to devastating outcomes including permanent disability opioid dependency and the inability to return to work In addition diagnosing CRPS can be a prolonged process due to the range of vague symptoms on presentation which can lead to delay in treatment and worsening of outcomes Patients with CRPS may require more follow-up and referrals which further burdens the healthcare system
The pathogenesis of CRPS is complex and not fully known evidence suggests nervous system sensitisation autonomic dysfunction and inflammatory changes There are numerous treatment options for CRPS though little high-quality evidence supports their efficacy These include but are not limited to oral anti-depressants parenteral lidocaine and corticosteroids surgical treatment with compressed nerve release counselling and occupational and physical therapy Vitamin C has been proposed as effective prophylaxis for CRPS in distal radius fractures but data have been conflicting with the most recent randomized controlled trial RCT in 2014 by Ekrol et al showing no difference in functional outcomes or rate of CRPS in patients with distal radius fractures given Vitamin C versus placebo
Given the prevalence of distal radius fractures in adults a relatively high CRPS incidence in this population and no established efficacious treatment options more research is needed to determine evidence-based and effective treatment options for this destructive condition Studies have identified that using glucocorticoids can potentially be effective and safe for treating patients with CRPS possibly due to the anti-inflammatory properties of glucocorticoids One retrospective study of patients undergoing surgery for terrible triad elbow complex elbow fracture dislocation injuries demonstrated improved elbow range of motion for patients receiving intraoperative dexamethasone and 6-day oral course of methylprednisolone compared to patients who did not with no increased postoperative infection Furthermore the anti-inflammatory nature of glucocorticoids deserves investigation for its potential to decrease opioid consumption after distal radius surgery
A variety of doses and duration of glucocorticoids have been used in studies to manage CRPS with a recent review article by Kwak et al showing starting doses between 30 mg to 100 mg of prednisolone Although glucocorticoids are known to be associated with adverse effects most are only seen with long term therapy In addition studies have shown that a short-course of glucocorticoids less than 3 to 4 weeks irrespective of dose do not require a tapering regimen and is not associated with increased risk of adrenal insufficiency While osteoporosis and fracture non-union are known adverse events of long-term glucocorticoid use this has not been demonstrated in literature for short-term use Moreover given the risk of non-union in distal radius fractures is exceedingly rare 02 this calls for less concern for using glucocorticoids in this population
Therefore evaluating prednisone a relatively cheap accessible and safe oral medication when used for a short duration as an anti-inflammatory and potential early treatment agent for CRPS in distal radius fractures in this pilot study may have implications for the complication profile and functional outcome for this common fracture
Research Design
This will be a pilot double-blind randomized control trial in patients who sustain a distal radius fracture treated operatively with a volar locked plate and identified as at risk of developing CRPS Follow up will be 6 months involving 4 study visits that correspond to standard post-operative clinic visits
Statistical Analysis
A power analysis assuming incidence of 20 CRPS and absolute risk reduction ARR of 10 with prophylaxis yielded a sample size of 199 patients per arm with 80 power and significance level α of 005 performed using online sample size calculator at clincalccomstatssamplesizeaspx Incidence and ARR were estimated based on previous RCTs assessing Vitamin C as prophylaxis for CRPS in distal radius fractures We aim to recruit 10 for this pilot study with 20 per arm placebo vs prednisone for a total of 40 patients
The CONSORT guidelines for reporting of randomized pilot and feasibility trial will be followed for the analysis and reporting of results An intention-to-treat analysis will be utilized
Primary Outcomes Descriptive statistics reported as count and percentage will be used to summarize the feasibility outcomes 95 CI Table 2 presents the traffic lights criteria for each outcome of the pilot study Green indicates feasible red indicates not feasible and yellow indicates likely feasible but will require adjustments to the protocol please see attached protocol
Secondary and Tertiary Outcomes Chi-square or Fishers Exact test will be used to compare the proportion of CRPS between groups Either Mann-Whitney U test or two-sample t test will be used for the other quantitative outcomes depending on the variable distribution Multivariable regression analysis will be conducted to test for associations between the intervention and each outcome controlling for differences in patient characteristics All P values will be 2-sided and statistical significance will be set at P 005 For this pilot trial formal hypothesis testing will not be performed as it is underpowered
Distal radius fractures are the most prevalent adult fracture accounting for 175 of all fractures Complex regional pain syndrome CRPS is a common complication that can occur in this population with a reported incidence of up to 32 CRPS can lead to permanent disability and is costly to the patient and to the healthcare system with an estimated cumulative outpatient and pain prescription cost of 42026 over 8 years after diagnosis In addition amidst the opioid epidemic the risk of increased opioid use in patients with CRPS prompts the need to find viable treatment strategies
While there have been various proposed treatment modalities evidence from randomized studies is lacking Several small studies retrospective and prospective case series have shown potential efficacy of glucocorticoids for the treatment of CRPS To our knowledge there are no randomized controlled trials that evaluate treatment of CRPS in distal radius fractures with glucocorticoids
The purpose of this pilot study is to evaluate a short course of oral prednisone as potential treatment for patients identified as developing early signs of CRPS after sustaining a distal radius fracture that was treated operatively We will examine feasibility metrics including patient recruitment rate adherence to allocation and protocol withdrawal from study and follow-through in order to inform design of a definitive clinical trial We will also assess the resolution of CRPS post-operative opioid use and any adverse events in patients who sustain a distal radius fracture after receiving prednisone vs placebo for 2 weeks post-operatively with 6 months follow up post injury
Hypothesis
We hypothesize that the proposed pilot trial will demonstrate feasibility of a future definitive trial
In addition we hypothesize that there will be higher rates of CRPS resolution lower amounts of opioid consumption and no increased adverse effects and better clinical outcomes in patients who receive prednisone treatment compared to those who received placebo However formal hypothesis testing will not be performed for this pilot trial
Justification
Developing CRPS after sustaining a distal radius fracture can lead to devastating outcomes including permanent disability opioid dependency and the inability to return to work In addition diagnosing CRPS can be a prolonged process due to the range of vague symptoms on presentation which can lead to delay in treatment and worsening of outcomes Patients with CRPS may require more follow-up and referrals which further burdens the healthcare system
The pathogenesis of CRPS is complex and not fully known evidence suggests nervous system sensitisation autonomic dysfunction and inflammatory changes There are numerous treatment options for CRPS though little high-quality evidence supports their efficacy These include but are not limited to oral anti-depressants parenteral lidocaine and corticosteroids surgical treatment with compressed nerve release counselling and occupational and physical therapy Vitamin C has been proposed as effective prophylaxis for CRPS in distal radius fractures but data have been conflicting with the most recent randomized controlled trial RCT in 2014 by Ekrol et al showing no difference in functional outcomes or rate of CRPS in patients with distal radius fractures given Vitamin C versus placebo
Given the prevalence of distal radius fractures in adults a relatively high CRPS incidence in this population and no established efficacious treatment options more research is needed to determine evidence-based and effective treatment options for this destructive condition Studies have identified that using glucocorticoids can potentially be effective and safe for treating patients with CRPS possibly due to the anti-inflammatory properties of glucocorticoids One retrospective study of patients undergoing surgery for terrible triad elbow complex elbow fracture dislocation injuries demonstrated improved elbow range of motion for patients receiving intraoperative dexamethasone and 6-day oral course of methylprednisolone compared to patients who did not with no increased postoperative infection Furthermore the anti-inflammatory nature of glucocorticoids deserves investigation for its potential to decrease opioid consumption after distal radius surgery
A variety of doses and duration of glucocorticoids have been used in studies to manage CRPS with a recent review article by Kwak et al showing starting doses between 30 mg to 100 mg of prednisolone Although glucocorticoids are known to be associated with adverse effects most are only seen with long term therapy In addition studies have shown that a short-course of glucocorticoids less than 3 to 4 weeks irrespective of dose do not require a tapering regimen and is not associated with increased risk of adrenal insufficiency While osteoporosis and fracture non-union are known adverse events of long-term glucocorticoid use this has not been demonstrated in literature for short-term use Moreover given the risk of non-union in distal radius fractures is exceedingly rare 02 this calls for less concern for using glucocorticoids in this population
Therefore evaluating prednisone a relatively cheap accessible and safe oral medication when used for a short duration as an anti-inflammatory and potential early treatment agent for CRPS in distal radius fractures in this pilot study may have implications for the complication profile and functional outcome for this common fracture
Research Design
This will be a pilot double-blind randomized control trial in patients who sustain a distal radius fracture treated operatively with a volar locked plate and identified as at risk of developing CRPS Follow up will be 6 months involving 4 study visits that correspond to standard post-operative clinic visits
Statistical Analysis
A power analysis assuming incidence of 20 CRPS and absolute risk reduction ARR of 10 with prophylaxis yielded a sample size of 199 patients per arm with 80 power and significance level α of 005 performed using online sample size calculator at clincalccomstatssamplesizeaspx Incidence and ARR were estimated based on previous RCTs assessing Vitamin C as prophylaxis for CRPS in distal radius fractures We aim to recruit 10 for this pilot study with 20 per arm placebo vs prednisone for a total of 40 patients
The CONSORT guidelines for reporting of randomized pilot and feasibility trial will be followed for the analysis and reporting of results An intention-to-treat analysis will be utilized
Primary Outcomes Descriptive statistics reported as count and percentage will be used to summarize the feasibility outcomes 95 CI Table 2 presents the traffic lights criteria for each outcome of the pilot study Green indicates feasible red indicates not feasible and yellow indicates likely feasible but will require adjustments to the protocol please see attached protocol
Secondary and Tertiary Outcomes Chi-square or Fishers Exact test will be used to compare the proportion of CRPS between groups Either Mann-Whitney U test or two-sample t test will be used for the other quantitative outcomes depending on the variable distribution Multivariable regression analysis will be conducted to test for associations between the intervention and each outcome controlling for differences in patient characteristics All P values will be 2-sided and statistical significance will be set at P 005 For this pilot trial formal hypothesis testing will not be performed as it is underpowered
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