Diazepam Use With Standard Management for Acute Low Back Pain

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02646124
• Collaborator: (none)
• Enrollment: 114
• Location: 1
• Arms: 2
• Duration (Months): 11
• Patients Per Site Per Month: 10.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Low Back Pain	Drug: Naproxen; Drug: Placebo; Drug: Diazepam	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Adding Diazepam to Standard Management of Acute, Non-radicular Low Back Pain. An Emergency Department Based Randomized Comparative Effectiveness Study
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diazepam Naproxen +Diazepam	Drug: Naproxen; Naproxen 500mg by mouth two times a day, #20; Drug: Diazepam; Diazepam 5mg capsules, 1-2 tabs by mouth two times a day, #28
Active Comparator: Placebo Naproxen + Placebo	Drug: Naproxen; Naproxen 500mg by mouth two times a day, #20; Drug: Placebo; 28 placebo capsules; Other Names: Placebo Diazepam

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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

4. 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?"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center	Bronx	New York	United States	10467

Sponsors and Collaborators

• Montefiore Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Benjamin W. Friedman, MD, principal investigator, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT02646124
• Other Study ID Numbers: 2015-4639
• First Posted: Jan 5, 2016
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by Benjamin W. Friedman, MD, principal investigator, Montefiore Medical Center: benzodiazepine
• Additional relevant MeSH terms: Back Pain; Low Back Pain; Naproxen; Diazepam

Study Results

Participant Flow

Arm/Group Title	Diazepam	Placebo
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
Period Title: Overall Study
STARTED	57	57
COMPLETED	57	55
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Diazepam	Placebo	Total
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules	Total of all reporting groups
Overall Participants	57	57	114
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34 (12)	38 (12)	36 (12)
Sex: Female, Male (Count of Participants)
Female	27 47.4%	24 42.1%	51 44.7%
Male	30 52.6%	33 57.9%	63 55.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	57 100%	57 100%	114 100%
Duration of Back Pain Prior to Study (hours) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [hours]	72	48	48

Outcome Measures

1. Primary Outcome

Title	Change in Functional Impairment as Measured by the Roland Morris Disability Questionnaire
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diazepam	Placebo
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
Measure Participants	57	55
Mean (95% Confidence Interval) [units on a scale]	11	11

2. Secondary Outcome

Title	Number of Participants With Moderate or Severe Pain, as Measured on an Ordinal Scale
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diazepam	Placebo
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
Measure Participants	57	55
Count of Participants [Participants]	18 31.6%	12 21.1%

3. Secondary Outcome

Title	Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diazepam	Placebo
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
Measure Participants	57	55
Count of Participants [Participants]	26 45.6%	25 43.9%

4. Secondary Outcome

Title	Number of Participants Who Required Analgesic Medication for Low Back Pain Within the Previous 72 Hours
Description	Patients needing any analgesic or LBP medication within the previous 72 hours
Time Frame	Assessed three months after emergency department discharge

Outcome Measure Data

Analysis Population Description

data not collected

Arm/Group Title	Diazepam	Placebo
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
Measure Participants	0	0

5. Secondary Outcome

Title	Participants Satisfied With Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diazepam	Placebo
Arm/Group Description	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	Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
Measure Participants	57	55
Count of Participants [Participants]	44 77.2%	37 64.9%

Adverse Events

Arm/Group Title	Diazepam		Placebo
Arm/Group Description	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		Naproxen + Placebo Naproxen: Naproxen 500mg by mouth two times a day, #20 Placebo: 28 placebo capsules
All Cause Mortality
	Diazepam		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/55 (0%)
Serious Adverse Events
	Diazepam		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Diazepam		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/57 (21.1%)		8/55 (14.5%)
Gastrointestinal disorders
Stomach irritation	1/57 (1.8%)	1	1/55 (1.8%)	1
General disorders
Other	6/57 (10.5%)	6	6/55 (10.9%)	6
Nervous system disorders
Drowsy	4/57 (7%)	4	1/55 (1.8%)	1
Dizzy	1/57 (1.8%)	1	0/55 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.