Low Back Pain
Conditions
Keywords
benzodiazepine
Brief summary
Given the poor pain and functional outcomes that persist beyond an Emergency Department (ED) visit for musculoskeletal low back pain (LBP), we propose a clinical trial to evaluate whether combining a benzodiazepine with an NSAID is more effective than nonsteroidal antiinflammatory drug (NSAID) monotherapy for the treatment of acute, non-traumatic, non-radicular low back pain.
Detailed description
Low back pain (LBP) causes 2.4% of visits to US emergency departments (ED) resulting in 2.7 million visits annually. In general, outcomes for these patients are poor. One week after ED discharge, 70% of patients report persistent back-pain related functional impairment and 69% report analgesic use within the previous 24 hours. Three months after the ED visit, 48% of these patients report functional impairment, 42% report moderate or severe pain, and 46% report persistent analgesic use. It is not clear how acute LBP should be treated. Non-steroidal anti-inflammatory drugs (NSAID) are guideline-supported, first line therapy for acute LBP. NSAIDs are more efficacious than placebo with regard to pain relief, global improvement, and requirement of analgesic medication but are not sufficient therapy for as many as ½ of ED patients, who continue to suffer despite therapy with NSAIDs. Treatment of LBP with multiple concurrent medications is common in the ED--emergency physicians often prescribe benzodiazepines, skeletal muscle relaxants, or opioids in combination with NSAIDs. However, work recently completed here at Montefiore has revealed that combining skeletal muscle relaxants or opioids with NSAIDs does not improve outcomes. It remains uncertain if adding benzodiazepines to NSAIDs improves LBP outcomes. Although benzodiazepines are used in 300,000 US ED visits for LBP annually, scant evidence exists to determine the appropriateness of this approach. Efficacy of benzodiazepines may be related to direct or centrally-mediated action on skeletal muscle or may instead work by mitigating anxiety about the condition or numbing a patient to the pain. Given the poor pain and functional outcomes that persist beyond an ED visit for musculoskeletal LBP, we propose a clinical trial to evaluate whether combining a benzodiazepine with an NSAID is more effective than NSAID monotherapy for the treatment of acute, non-traumatic, non-radicular low back pain. Specifically, we will evaluate the following hypothesis: A daily regimen of naproxen + diazepam will provide greater relief of LBP than naproxen + placebo one week after an ED visit, as measured by the Roland Morris Disability Questionnaire.
Interventions
DRUGNaproxen
Naproxen 500mg by mouth two times a day, #20
DRUGPlacebo
28 placebo capsules
DRUGDiazepam
Diazepam 5mg capsules, 1-2 tabs by mouth two times a day, #28
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* Present to ED primary for management of LBP, defined as pain originating between the lower border of the scapulae and the upper gluteal folds. Flank pain, that is pain originating from tissues lateral to the paraspinal muscles, will not be included. * Absence of non-musculoskeletal etiology of low back, such as urinary tract infection, cystic ovarian disease, or influenza like illness. The primary clinical diagnosis, at the conclusion of the ED visit, must be a diagnosis consistent with non-traumatic, non-radicular, musculoskeletal LBP. * Patient is to be discharged home. Patients admitted to the hospital are more likely to be treated with parenteral medication and therefore are not appropriate for this study. * Age 21-69 Enrollment will be limited to adults younger than 70 years because of the increased risk of adverse medication effects in the elderly. * Non-radicular pain: pain cannot radiate below the gluteal folds in a radicular pattern. Patients with non-radicular pain extending below the gluteal folds will not be excluded * Pain duration \<2 weeks (336 hours). Patients with more than two weeks of pain are at increased risk of poor pain and functional outcomes.(2) * Prior to the acute attack of LBP, back pain cannot have occurred once per month or more frequently. Patients with more frequent back pain are at increased risk of poor pain and functional outcomes.(2) * Non-traumatic LBP: no substantial and direct trauma to the back within the previous month * Functionally impairing back pain: A baseline score of \> 5 on the Roland-Morris Disability Questionnaire
Exclusion criteria
* -Not available for follow-up * Pregnant or breast-feeding * Chronic pain syndrome defined as use of any analgesic medication on a daily or near-daily basis * Allergic to or intolerant of investigational medications * Contra-indications to non-steroidal anti-inflammatory drugs: peptic ulcer disease, history of gastro-intestinal bleeding, congestive heart failure, advanced renal disease, aspirin sensitive asthma * Contra-indications to diazepam: glaucoma, myasthenia gravis, cirrhosis, sleep apnea, history of alcoholism or substance abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire | Between baseline and one week after emergency department discharge | The Roland Morris Disability Questionnaire (RMDQ) is a 24 item instrument that evaluates the impact of low back pain on one's daily life. It is most sensitive for patients with mild to moderate disability due to acute, sub-acute or chronic low back pain. Each question can be answered as either a yes or no. The score ranges from 0 to 24 where a higher score reflects greater impairment and, therefore, worsening in the quality of life. The change in RMDQ is obtained by subtracting the RMDQ score at one week after discharge from the baseline score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Moderate or Severe Pain, as Measured on an Ordinal Scale | 1 week after discharge from emergency department | Patients with moderate or serve pain. Worst Lower Back Pain (LBP) over the previous 24 hours, using a four point ordinal scale: severe, moderate, mild, or none. |
| Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 24 Hours | One week after discharge from the emergency department | Telephone questionnaire is used to assess patients needing any analgesic or low back pain medication within the previous 24 hours. |
| Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 72 Hours | Assessed three months after emergency department discharge | Patients needing any analgesic or LBP medication within the previous 72 hours |
| Participants Satisfied With Treatment | 1 week | Participants who answered Yes when asked the question Do you want to receive the same combination of medications during a subsequent visit to the ER? |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diazepam Naproxen +Diazepam
Naproxen: Naproxen 500mg by mouth two times a day, #20
Diazepam: Diazepam 5mg capsules, 1-2 tabs by mouth two times a day,, #28 | 57 |
| Placebo Naproxen + Placebo
Naproxen: Naproxen 500mg by mouth two times a day, #20
Placebo: 28 placebo capsules | 57 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Diazepam | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 34 Years STANDARD_DEVIATION 12 | 38 Years STANDARD_DEVIATION 12 | 36 Years STANDARD_DEVIATION 12 |
| Duration of Back Pain Prior to Study | 72 hours | 48 hours | 48 hours |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 57 Participants | 57 Participants | 114 Participants |
| Sex: Female, Male Female | 27 Participants | 24 Participants | 51 Participants |
| Sex: Female, Male Male | 30 Participants | 33 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 55 |
| other Total, other adverse events | 12 / 57 | 8 / 55 |
| serious Total, serious adverse events | 0 / 57 | 0 / 55 |
Outcome results
Primary
Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire
The Roland Morris Disability Questionnaire (RMDQ) is a 24 item instrument that evaluates the impact of low back pain on one's daily life. It is most sensitive for patients with mild to moderate disability due to acute, sub-acute or chronic low back pain. Each question can be answered as either a yes or no. The score ranges from 0 to 24 where a higher score reflects greater impairment and, therefore, worsening in the quality of life. The change in RMDQ is obtained by subtracting the RMDQ score at one week after discharge from the baseline score.
Time frame: Between baseline and one week after emergency department discharge
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diazepam | Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire | 11 units on a scale |
| Placebo | Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire | 11 units on a scale |
Secondary
Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 24 Hours
Telephone questionnaire is used to assess patients needing any analgesic or low back pain medication within the previous 24 hours.
Time frame: One week after discharge from the emergency department
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diazepam | Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 24 Hours | 26 Participants |
| Placebo | Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 24 Hours | 25 Participants |
Secondary
Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 72 Hours
Patients needing any analgesic or LBP medication within the previous 72 hours
Time frame: Assessed three months after emergency department discharge
Population: data not collected
Secondary
Number of Participants With Moderate or Severe Pain, as Measured on an Ordinal Scale
Patients with moderate or serve pain. Worst Lower Back Pain (LBP) over the previous 24 hours, using a four point ordinal scale: severe, moderate, mild, or none.
Time frame: 1 week after discharge from emergency department
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diazepam | Number of Participants With Moderate or Severe Pain, as Measured on an Ordinal Scale | 18 Participants |
| Placebo | Number of Participants With Moderate or Severe Pain, as Measured on an Ordinal Scale | 12 Participants |
Secondary
Participants Satisfied With Treatment
Participants who answered Yes when asked the question Do you want to receive the same combination of medications during a subsequent visit to the ER?
Time frame: 1 week
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diazepam | Participants Satisfied With Treatment | 44 Participants |
| Placebo | Participants Satisfied With Treatment | 37 Participants |