Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06603662
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-17
Brief Title:
Systemic Oral Glucocorticoids for the Treatment of Acute Osteoarthritis Pain in the Emergency Department
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Systemic Oral Glucocorticoids for the Treatment of Acute Osteoarthritis Pain in the Emergency Department
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this clinical trial is to compare the analgesic effects relief of pain of glucocorticoids steroids and pain medication versus pain medication alone in adult patients presenting to the emergency department with joint pain due to osteoarthritis Steroids are drugs that can reduce inflammation and are used commonly for many different medical conditions
In brief the central aims of the study are to
1 Assess the efficacy of adding oral glucocorticoid medications to the standard pain medications used to treat the pain of osteoarthritis
2 Assess the safety and tolerability of oral glucocorticoid medication for the short-term treatment of osteoarthritis pain
We hypothesize that 1 The addition of glucocorticoids to standard pain medications will improve reported pain scores at 3 days following the initiation of treatment compared to standard pain medications alone and 2 The use of glucocorticoids will be well tolerated
Participants in the study will be randomized like flipping a coin into one of three groups
1 Study Group 1 Control receiving placebo pills no active ingredient once a day for 5 days plus ibuprofen pain medication for 5 days
2 Study Group 2 Intervention A who will receive prednisone steroid once a day for 5 days plus ibuprofen pain medication for 5 days
3 Study Group 3 Intervention B who will receive one dose of dexamethasone steroid followed by placebo pills no active ingredient once a day for 4 days plus ibuprofen pain medication for 5 days
In all groups acetaminophen a different pain medication can be taken as needed for pain that is not controlled with ibuprofen
Participants will
Receive follow up phone calls at 1 3 7 and 14 days
Report pain scores related to joint pain
Report the number of pills taken of the various medications used in the study
Report any adverse events incurred during the follow up period
In brief the central aims of the study are to
1 Assess the efficacy of adding oral glucocorticoid medications to the standard pain medications used to treat the pain of osteoarthritis
2 Assess the safety and tolerability of oral glucocorticoid medication for the short-term treatment of osteoarthritis pain
We hypothesize that 1 The addition of glucocorticoids to standard pain medications will improve reported pain scores at 3 days following the initiation of treatment compared to standard pain medications alone and 2 The use of glucocorticoids will be well tolerated
Participants in the study will be randomized like flipping a coin into one of three groups
1 Study Group 1 Control receiving placebo pills no active ingredient once a day for 5 days plus ibuprofen pain medication for 5 days
2 Study Group 2 Intervention A who will receive prednisone steroid once a day for 5 days plus ibuprofen pain medication for 5 days
3 Study Group 3 Intervention B who will receive one dose of dexamethasone steroid followed by placebo pills no active ingredient once a day for 4 days plus ibuprofen pain medication for 5 days
In all groups acetaminophen a different pain medication can be taken as needed for pain that is not controlled with ibuprofen
Participants will
Receive follow up phone calls at 1 3 7 and 14 days
Report pain scores related to joint pain
Report the number of pills taken of the various medications used in the study
Report any adverse events incurred during the follow up period
Detailed Description:
BACKGROUND
Osteoarthritis OA constitutes a significant disease burden both within the United States US and globally Recent data shows that upwards of 527 million people worldwide were affected by OA in 2019 Data from 2001-2005 suggests that over 77 million ambulatory visits in the US were attributed to arthritic and rheumatological disorders of which OA was the predominant etiology Patients often present to the emergency department ED with complaints of acute pain related to OA
Current guidelines recommend both lifestyle interventions and pharmacological interventions for the treatment of OA-related pain Oral non-steroidal anti-inflammatory drugs NSAIDs such as ibuprofen ketorolac and diclofenac remain first-line agents for the treatment of OA-related pain with strong recommendations for this intervention from the American College of Rheumatology Arthritis Foundation In contrast the evidence for topical NSAID use for the treatment of OA pain is inconsistent regarding their benefit
Glucocorticosteroids or glucocorticoids are commonly used for their anti-inflammatory effects Intraarticular glucocorticoid injections are a recommended adjunct treatment for OA-related pain refractory to NSAIDs The majority of clinical practice guidelines support their use in OA with recent data showing significant improvement in pain scores following intraarticular glucocorticoid injections Although commonly used in the outpatient setting intraarticular injections for OA are used less frequently in the ED This is due to the time required to perform the procedure the need for subsequent follow-up and technical considerations
Compared to oral administration intraarticular glucocorticoid injections have less systemic absorption and the potential for decreased adverse effects however oral glucocorticoid regimens have been shown to be well tolerated when given in short courses for acute pain A Cochrane review examining short-term oral glucocorticoid use for the treatment of radicular low back pain found no association with significant adverse effects including hyperglycemia
The use of glucocorticoid injections in OA has been studied robustly but there has been very little research examining the utility of oral systemic glucocorticoids in the treatment of acute OA-related pain The current literature is largely limited to OA specifically affecting the hand and does not include ED patients Dossing et al found that oral corticosteroids were effective in improving pain functional status and quality of life in patients with hand OA when compared to placebo Similarly a systematic review noted that oral glucocorticoid use for the treatment of hand OA reduced pain and improved functional status at 4-6 weeks Dorleijn et al did not study oral glucocorticoids specifically but noted that intramuscular injections of glucocorticoids were more effective when compared to placebo for the reduction of negative symptoms in hip OA at 2 weeks and beyond Surprisingly no such positive results were observed with intraarticular glucocorticoid injections
We aim to examine the effectiveness and safety of adding short-term oral systemic glucocorticoids to a standardized NSAID regimen in adult ED patients presenting with acute pain due to OA
OBJECTIVES
1 Assess the efficacy of adding oral glucocorticoids prednisone or dexamethasone to the standard treatment of acute OA pain with NSAIDs
2 Assess the safety and tolerability of systemic oral glucocorticoids for the short-term treatment of acute OA pain in ED patients
We hypothesize the combination of oral glucocorticoids and NSAIDs will result in improved pain control for acute OA pain compared to NSAIDs alone and will be well tolerated
STUDY DESIGN
This will be a randomized controlled single-blinded superiority trial consisting of adult patients presenting to the WellSpan York Hospital ED with acute large joint monoarticular pain related to underlying OA Informed consent will be obtained by a member of the study team prior to data collection or study procedures
Patients enrolled in the study will be randomized into one of three groups in a 111 ratio Group 1 control will receive ibuprofen 600 mg every 8 hours plus a placebo no active ingredient pill daily x 5 days Group 2 intervention A will receive ibuprofen 600 mg every 8 hours plus prednisone 50 mg daily x 5 days Group 3 intervention B will receive ibuprofen 600 mg every 8 hours x 5 days plus a single dose of oral dexamethasone 10 mg during the index ED visit then a placebo no active ingredient pill daily x 4 days Subjects in all three arms will have the option to take oral acetaminophen 975 mg every 8 hours as needed for uncontrolled pain
Subjects will be followed up by phone at 1 day 3 days 7 days and 14 days and assessed for pain adverse events and other outcomes Chart review will be performed at 14 and 28 days to assess for other adverse events All research data will be documented on standardized data collection forms
DATA ANALYSIS
Descriptive statistics will be reported as meansmedians with standard deviationinterquartile range for continuous variables and proportions with percentages for categorical variables Differences in continuous outcome variables between the three study groups will be compared via one way ANOVA Subsequent pairwise comparisons will utilize the Student T-test for parametric data and the Mann-Whitney U test for non-parametric data with associated 95 confidence intervals Differences in dichotomous variables between groups will be compared via chi-squared or Fishers exact tests as appropriate Primary analysis will be conducted on an intention-to-treat basis however per protocol sensitivity analysis is also planned Interrater reliability for follow-up data collection from the medical record will be assessed via Cohens kappa p lt 005 will be considered statistically significant
POWER CALCULATIONS AND PLANNED SAMPLE SIZE
Power calculations are based on prior published literature on patients presenting with pain related to hip OA Assuming an approximate baseline pain VAS mean5SD22 and an expected mean change in numerical pain score at 72-hours change of 05 in the control group and 15 in the steroid groups we need to enroll 59 subjects per arm to achieve 80 power at alpha005 These assumptions also align with the clinically significant margin of difference in pain score 10 established in prior studies Allowing for 5 attrition and need for a total enrollment equally divisible into 3 arms we plan to enroll a total of 192 subjects 64 per arm randomized 111
RISKS TO SUBJECTS
While NSAIDs and glucocorticoids are very frequently administered medications there are risks associated with their use NSAIDs have been associated with gastricpeptic irritationulcers renal adverse effects kidney injury electrolytefluid disorders renal papillary necrosis and interstitial nephritis and cardiovascular adverse effects myocardial infarction thromboembolic events and atrial fibrillation as well as hepatic or hematologic effects however significant adverse effects from ibuprofen are rare particularly when taken in a short course in the absence of contraindications Ibuprofen is available over the counter without a prescription and is generally very well tolerated
Glucocorticoids have been associated with adverse effects affecting the musculoskeletal system osteoporosis myopathy osteonecrosis endocrine system elevated blood glucose cushingoid features weight gain hirsutismalopecia cardiovascular system hypertension fluid retention arrhythmias and gastrointestinal system ulcers GIB They are also associated with increased rates of infection and neuropsychiatric effects such as anxiety depression psychosis and sleep disturbances However the incidence and severity of these effects are linked to the glucocorticoid dose and duration short courses are very commonly used in clinical practice and generally well tolerated
There is a slight risk of the participants privacy or confidentiality being breached Standard precautions will be taken to ensure privacy and confidentiality are maintained during the study There are no additional required study visits
COSTS AND COMPENSATION
No compensation will be given to participants There will be no research-related costs to the patient Study medications will be provided to participants at no cost
POTENTIAL BENEFITS TO SUBJECTS
Subjects may receive clinical benefit from the additional anti-inflammatory effect provided by glucocorticoids however determining the effectiveness of glucocorticoids in this clinical application is the purpose of the study Subjects may not directly benefit from participation but may help to improve the care of patients suffering from acute OA-related pain in the future
Osteoarthritis OA constitutes a significant disease burden both within the United States US and globally Recent data shows that upwards of 527 million people worldwide were affected by OA in 2019 Data from 2001-2005 suggests that over 77 million ambulatory visits in the US were attributed to arthritic and rheumatological disorders of which OA was the predominant etiology Patients often present to the emergency department ED with complaints of acute pain related to OA
Current guidelines recommend both lifestyle interventions and pharmacological interventions for the treatment of OA-related pain Oral non-steroidal anti-inflammatory drugs NSAIDs such as ibuprofen ketorolac and diclofenac remain first-line agents for the treatment of OA-related pain with strong recommendations for this intervention from the American College of Rheumatology Arthritis Foundation In contrast the evidence for topical NSAID use for the treatment of OA pain is inconsistent regarding their benefit
Glucocorticosteroids or glucocorticoids are commonly used for their anti-inflammatory effects Intraarticular glucocorticoid injections are a recommended adjunct treatment for OA-related pain refractory to NSAIDs The majority of clinical practice guidelines support their use in OA with recent data showing significant improvement in pain scores following intraarticular glucocorticoid injections Although commonly used in the outpatient setting intraarticular injections for OA are used less frequently in the ED This is due to the time required to perform the procedure the need for subsequent follow-up and technical considerations
Compared to oral administration intraarticular glucocorticoid injections have less systemic absorption and the potential for decreased adverse effects however oral glucocorticoid regimens have been shown to be well tolerated when given in short courses for acute pain A Cochrane review examining short-term oral glucocorticoid use for the treatment of radicular low back pain found no association with significant adverse effects including hyperglycemia
The use of glucocorticoid injections in OA has been studied robustly but there has been very little research examining the utility of oral systemic glucocorticoids in the treatment of acute OA-related pain The current literature is largely limited to OA specifically affecting the hand and does not include ED patients Dossing et al found that oral corticosteroids were effective in improving pain functional status and quality of life in patients with hand OA when compared to placebo Similarly a systematic review noted that oral glucocorticoid use for the treatment of hand OA reduced pain and improved functional status at 4-6 weeks Dorleijn et al did not study oral glucocorticoids specifically but noted that intramuscular injections of glucocorticoids were more effective when compared to placebo for the reduction of negative symptoms in hip OA at 2 weeks and beyond Surprisingly no such positive results were observed with intraarticular glucocorticoid injections
We aim to examine the effectiveness and safety of adding short-term oral systemic glucocorticoids to a standardized NSAID regimen in adult ED patients presenting with acute pain due to OA
OBJECTIVES
1 Assess the efficacy of adding oral glucocorticoids prednisone or dexamethasone to the standard treatment of acute OA pain with NSAIDs
2 Assess the safety and tolerability of systemic oral glucocorticoids for the short-term treatment of acute OA pain in ED patients
We hypothesize the combination of oral glucocorticoids and NSAIDs will result in improved pain control for acute OA pain compared to NSAIDs alone and will be well tolerated
STUDY DESIGN
This will be a randomized controlled single-blinded superiority trial consisting of adult patients presenting to the WellSpan York Hospital ED with acute large joint monoarticular pain related to underlying OA Informed consent will be obtained by a member of the study team prior to data collection or study procedures
Patients enrolled in the study will be randomized into one of three groups in a 111 ratio Group 1 control will receive ibuprofen 600 mg every 8 hours plus a placebo no active ingredient pill daily x 5 days Group 2 intervention A will receive ibuprofen 600 mg every 8 hours plus prednisone 50 mg daily x 5 days Group 3 intervention B will receive ibuprofen 600 mg every 8 hours x 5 days plus a single dose of oral dexamethasone 10 mg during the index ED visit then a placebo no active ingredient pill daily x 4 days Subjects in all three arms will have the option to take oral acetaminophen 975 mg every 8 hours as needed for uncontrolled pain
Subjects will be followed up by phone at 1 day 3 days 7 days and 14 days and assessed for pain adverse events and other outcomes Chart review will be performed at 14 and 28 days to assess for other adverse events All research data will be documented on standardized data collection forms
DATA ANALYSIS
Descriptive statistics will be reported as meansmedians with standard deviationinterquartile range for continuous variables and proportions with percentages for categorical variables Differences in continuous outcome variables between the three study groups will be compared via one way ANOVA Subsequent pairwise comparisons will utilize the Student T-test for parametric data and the Mann-Whitney U test for non-parametric data with associated 95 confidence intervals Differences in dichotomous variables between groups will be compared via chi-squared or Fishers exact tests as appropriate Primary analysis will be conducted on an intention-to-treat basis however per protocol sensitivity analysis is also planned Interrater reliability for follow-up data collection from the medical record will be assessed via Cohens kappa p lt 005 will be considered statistically significant
POWER CALCULATIONS AND PLANNED SAMPLE SIZE
Power calculations are based on prior published literature on patients presenting with pain related to hip OA Assuming an approximate baseline pain VAS mean5SD22 and an expected mean change in numerical pain score at 72-hours change of 05 in the control group and 15 in the steroid groups we need to enroll 59 subjects per arm to achieve 80 power at alpha005 These assumptions also align with the clinically significant margin of difference in pain score 10 established in prior studies Allowing for 5 attrition and need for a total enrollment equally divisible into 3 arms we plan to enroll a total of 192 subjects 64 per arm randomized 111
RISKS TO SUBJECTS
While NSAIDs and glucocorticoids are very frequently administered medications there are risks associated with their use NSAIDs have been associated with gastricpeptic irritationulcers renal adverse effects kidney injury electrolytefluid disorders renal papillary necrosis and interstitial nephritis and cardiovascular adverse effects myocardial infarction thromboembolic events and atrial fibrillation as well as hepatic or hematologic effects however significant adverse effects from ibuprofen are rare particularly when taken in a short course in the absence of contraindications Ibuprofen is available over the counter without a prescription and is generally very well tolerated
Glucocorticoids have been associated with adverse effects affecting the musculoskeletal system osteoporosis myopathy osteonecrosis endocrine system elevated blood glucose cushingoid features weight gain hirsutismalopecia cardiovascular system hypertension fluid retention arrhythmias and gastrointestinal system ulcers GIB They are also associated with increased rates of infection and neuropsychiatric effects such as anxiety depression psychosis and sleep disturbances However the incidence and severity of these effects are linked to the glucocorticoid dose and duration short courses are very commonly used in clinical practice and generally well tolerated
There is a slight risk of the participants privacy or confidentiality being breached Standard precautions will be taken to ensure privacy and confidentiality are maintained during the study There are no additional required study visits
COSTS AND COMPENSATION
No compensation will be given to participants There will be no research-related costs to the patient Study medications will be provided to participants at no cost
POTENTIAL BENEFITS TO SUBJECTS
Subjects may receive clinical benefit from the additional anti-inflammatory effect provided by glucocorticoids however determining the effectiveness of glucocorticoids in this clinical application is the purpose of the study Subjects may not directly benefit from participation but may help to improve the care of patients suffering from acute OA-related pain in the future
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