- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01583985
Strategies for Prescribing Analgesics Comparative Effectiveness Trial (SPACE)
Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background: Chronic musculoskeletal pain conditions are among the most common problems seen in primary care. As the importance of these conditions for the health of individuals and society has been increasingly recognized, use of long-term opioid therapy for chronic musculoskeletal pain has grown exponentially. Unfortunately, research has not kept pace with this change in prescribing practice. Although evidence supports the ability of opioid analgesics to produce short-term reductions in pain intensity, long-term trials evaluating opioid effectiveness are not available. Evidence for effects of opioids on function and quality of life are limited, but observational data indicate that many patients treated with long-term opioids continue to experience severe pain and functional limitations. Furthermore, the long-term harms of opioids are poorly described in the literature. Preliminary investigations suggest a variety of potential harms related to opioid therapy, but the incidence and severity of these harms have not been well-quantified.
Objectives: The main objective of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial is to compare benefits and harms of two prescribing strategies: 1) an opioid-intensive strategy that uses strong opioids, such as morphine, early in treatment, and 2) an opioid-avoidant strategy that optimizes non-opioid medications while delaying and minimizing opioid use. SPACE will evaluate, over 12 months, 1) effects of opioid-intensive versus opioid-avoidant prescribing strategies on pain-related function and pain intensity and 2) adverse effects of opioid-intensive versus opioid-avoidant prescribing strategies, including adverse medication-related symptoms, clinically important adverse events, and changes in physical and cognitive performance. Secondarily, the investigators will examine effects of the two prescribing strategies on health-related quality of life, pain sensitivity, and aberrant drug-related behaviors. The investigators will also conduct a secondary qualitative analysis to better understand patients' perceptions of their response to the interventions and of the value of intervention components.
Methods: SPACE is a pragmatic randomized clinical trial designed to compare the benefits and harms over 12 months of two clinically-relevant prescribing strategies for chronic musculoskeletal pain. Eligible Veterans will be those seen in primary care for chronic back or lower-extremity (hip or knee) arthritis pain who have moderate-severe pain intensity and interference with function. Those currently receiving chronic daily opioid therapy will be excluded. Participants will be randomized to the opioid-intensive (n=138) or the opioid-avoidant (n=138) arm, with stratification by primary pain location (back or hip/knee). Medications in each arm will be adjusted to target improvement in pain, while considering individual patient preferences and responses. Interventions will be delivered in a care management model using the randomly assigned prescribing strategies, automated symptom monitoring, and a structured decision-making approach to guide medication adjustment. Outcome assessors masked to treatment assignment will conduct interviews to assess patient-reported outcomes at 0, 3, 6, 9, and 12 months and will assess physical performance and cognitive function at 0, 6, and 12 months. For the primary outcome, the Brief Pain Inventory (BPI) Interference scale, the study will have 80% power to detect a 1 point difference between groups, assuming 2-sided alpha=0.05 and 20% attrition. Analysis will use an intent-to-treat approach, including all participants in the arm to which they were originally assigned.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Minnesota
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Minneapolis, Minnesota, United States, 55417
- Minneapolis VA Health Care System, Minneapolis, MN
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Veterans with chronic back or lower extremity osteoarthritis pain with moderate-severe intensity and interference with function despite analgesic therapy.
Exclusion Criteria:
- schizophrenia, bipolar disorder, or other psychosis;
- moderately severe cognitive impairment;
- anticipated back, knee, or hip surgery within 12 months;
- anticipated life expectancy of less than 12 months;
- current chronic daily opioid therapy;
- absolute contraindications to either prescribing strategy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Opioid-intensive
Opioid-intensive prescribing strategy
|
The opioid-intensive arm emphasizes early use of strong opioid analgesics.
Medications will be individually adjusted according to patient preferences and responses.
|
Active Comparator: Opioid-avoidant
Opioid-avoidant prescribing strategy
|
The opioid-avoidant prescribing strategy emphasizes non-opioid medications from several drug classes.
Medications will be individually adjusted according to patient preferences and responses.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brief Pain Inventory Interference Scale
Time Frame: 3 months, 6 months, 9 months, and 12 months
|
Measure of pain-related functional interference (range 0-10; higher score is worse)
|
3 months, 6 months, 9 months, and 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brief Pain Inventory Severity Scale
Time Frame: 3 months, 6 months, 9 months, and 12 months
|
Measure of pain intensity (range 0-10; higher score is worse)
|
3 months, 6 months, 9 months, and 12 months
|
Medication-related Symptom Checklist
Time Frame: 3 months, 6 months, 9 months, and 12 months
|
Checklist of bothersome medication-related symptoms (0-19, higher number = more symptoms)
|
3 months, 6 months, 9 months, and 12 months
|
Falls
Time Frame: 12 months
|
Number of falls in 12 months after enrollment
|
12 months
|
Hospitalizations
Time Frame: 12 months
|
All cause, EMR-confirmed hospitalizations
|
12 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Erin E. Krebs, MD MPH, Minneapolis VA Health Care System, Minneapolis, MN
Publications and helpful links
General Publications
- Kroenke K, Stump TE, Kean J, Krebs EE, Damush TM, Bair MJ, Monahan PO. Diagnostic operating characteristics of PROMIS scales in screening for depression. J Psychosom Res. 2021 Aug;147:110532. doi: 10.1016/j.jpsychores.2021.110532. Epub 2021 May 25.
- Kroenke K, Stump TE, Chen CX, Kean J, Damush TM, Bair MJ, Krebs EE, Monahan PO. Responsiveness of PROMIS and Patient Health Questionnaire (PHQ) Depression Scales in three clinical trials. Health Qual Life Outcomes. 2021 Feb 4;19(1):41. doi: 10.1186/s12955-021-01674-3.
- Kroenke K, Stump TE, Chen CX, Kean J, Bair MJ, Damush TM, Krebs EE, Monahan PO. Minimally important differences and severity thresholds are estimated for the PROMIS depression scales from three randomized clinical trials. J Affect Disord. 2020 Apr 1;266:100-108. doi: 10.1016/j.jad.2020.01.101. Epub 2020 Jan 23.
- Krebs EE, Jensen AC, Nugent S, DeRonne B, Rutks I, Leverty D, Gravely A, Noorbaloochi S, Bair MJ, Kroenke K. Design, recruitment outcomes, and sample characteristics of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial. Contemp Clin Trials. 2017 Nov;62:130-139. doi: 10.1016/j.cct.2017.09.003. Epub 2017 Sep 8.
- Matthias MS, Donaldson MT, Jensen AC, Krebs EE. "I Was a Little Surprised": Qualitative Insights From Patients Enrolled in a 12-Month Trial Comparing Opioids With Nonopioid Medications for Chronic Musculoskeletal Pain. J Pain. 2018 Sep;19(9):1082-1090. doi: 10.1016/j.jpain.2018.04.008. Epub 2018 Apr 30.
- Koffel E, Kats AM, Kroenke K, Bair MJ, Gravely A, DeRonne B, Donaldson MT, Goldsmith ES, Noorbaloochi S, Krebs EE. Sleep Disturbance Predicts Less Improvement in Pain Outcomes: Secondary Analysis of the SPACE Randomized Clinical Trial. Pain Med. 2020 Jun 1;21(6):1162-1167. doi: 10.1093/pm/pnz221.
- Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, Kroenke K, Bair MJ, Noorbaloochi S. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. JAMA. 2018 Mar 6;319(9):872-882. doi: 10.1001/jama.2018.0899.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IIR 11-125
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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