An interventional study of Opioid-intensive prescribing strategy and Opioid-avoidant prescribing strategy in Back Pain and Osteoarthritis, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-03-06.
Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Treatment
Chronic musculoskeletal pain conditions are among the most prevalent conditions in VA primary care. Over the past two decades, improved clinical attention to pain has been associated with exponentially greater use of long-term opioid therapy for chronic non-cancer pain, both within and outside the VA system. Despite this change in practice, the proper place of opioids in chronic pain management continues to be controversial because research has not demonstrated the long-term safety and effectiveness of opioids for chronic musculoskeletal pain. The Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial will fill a critical gap in the evidence by comparing effectiveness and harms of two clinically relevant analgesic prescribing strategies-one that emphasizes early use of strong opioids and one that delays and minimizes opioid use-for Veterans with chronic back, hip, or knee pain. SPACE is designed to be highly relevant to clinical decision-making in VA primary care and to produce knowledge that will improve the lives of Veterans living with chronic pain.
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.
4,399 studies on the registry are indexed under Osteoarthritis; 583 are open to participants now.
This study's enrollment of 265 is above the median of 70 across 3,440 interventional studies indexed under Osteoarthritis.
Browse Osteoarthritis studies →VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.
Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Opioid-intensive prescribing strategy
Other: Opioid-intensive prescribing strategy
Opioid-avoidant prescribing strategy
Other: Opioid-avoidant prescribing strategy
The opioid-intensive arm emphasizes early use of strong opioid analgesics. Medications will be individually adjusted according to patient preferences and responses.
The opioid-avoidant prescribing strategy emphasizes non-opioid medications from several drug classes. Medications will be individually adjusted according to patient preferences and responses.
Brief Pain Inventory Interference Scale
Measure of pain-related functional interference (range 0-10; higher score is worse)
Time frame: 3 months, 6 months, 9 months, and 12 months
Brief Pain Inventory Severity Scale
Measure of pain intensity (range 0-10; higher score is worse)
Time frame: 3 months, 6 months, 9 months, and 12 months
Medication-related Symptom Checklist
Checklist of bothersome medication-related symptoms (0-19, higher number = more symptoms)
Time frame: 3 months, 6 months, 9 months, and 12 months
Falls
Number of falls in 12 months after enrollment
Time frame: 12 months
Hospitalizations
All cause, EMR-confirmed hospitalizations
Time frame: 12 months
| Milestone | Opioid | Non-opioid |
|---|---|---|
| Started | 120 | 120 |
| Included in primary analysis | 119 | 119 |
| Completed | 117 | 117 |
| Not completed | 3 | 3 |
Measure of pain-related functional interference (range 0-10; higher score is worse)
| units on a scale | Opioid | Non-opioid |
|---|---|---|
| 3 months | 3.7 ± 2.1 | 3.7 ± 2.2 |
| 6 months | 3.4 ± 2.1 | 3.6 ± 2.4 |
| 9 months | 3.6 ± 2.2 | 3.3 ± 2.4 |
| 12 months | 3.4 ± 2.5 | 3.3 ± 2.6 |
Measure of pain intensity (range 0-10; higher score is worse)
| units on a scale | Opioid | Non-opioid |
|---|---|---|
| 3 months | 4.3 ± 1.8 | 4.0 ± 1.7 |
| 6 months | 4.1 ± 1.8 | 4.1 ± 1.9 |
| 9 months | 4.2 ± 1.7 | 3.6 ± 1.7 |
| 12 months | 4.0 ± 2.0 | 3.5 ± 1.9 |
Checklist of bothersome medication-related symptoms (0-19, higher number = more symptoms)
| symptoms | Opioid | Non-opioid |
|---|---|---|
| 3 months | 2.3 ± 2.5 | 1.3 ± 1.8 |
| 6 months | 2.1 ± 2.7 | 1.3 ± 2.3 |
| 9 months | 1.9 ± 2.8 | 0.9 ± 1.9 |
| 12 months | 1.8 ± 2.6 | 0.9 ± 1.8 |
Number of falls in 12 months after enrollment
| Participants | Opioid | Non-opioid |
|---|---|---|
| No falls | 63 | 63 |
| 1 fall | 26 | 17 |
| 2 or more falls | 29 | 39 |
All cause, EMR-confirmed hospitalizations
| Participants | Opioid | Non-opioid |
|---|---|---|
| No hospitalizations | 99 | 99 |
| 1 hospitalization | 15 | 16 |
| 2 or more hospitalizations | 6 | 5 |
Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Opioid | 0/120 (0%) | 19/120 (15.8%) | 58/120 (48.3%) |
| Non-opioid | 0/120 (0%) | 22/120 (18.3%) | 49/120 (40.8%) |
| Event | Opioid | Non-opioid |
|---|---|---|
| HospitalizationGeneral disorders | 19/120 | 22/120 |
| Event | Opioid | Non-opioid |
|---|---|---|
| Emergency Department visitsGeneral disorders | 58/120 | 49/120 |
| Age, Categorical(Participants) | Opioid | Non-opioid | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 72 | 64 | 136 |
| >=65 years | 48 | 56 | 104 |
| Age, Continuous(years) | Opioid | Non-opioid | Total |
|---|---|---|---|
| Mean | 56.8 ± 13.3 | 59.7 ± 14.0 | 58.3 ± 13.7 |
| Sex: Female, Male(Participants) | Opioid | Non-opioid | Total |
|---|---|---|---|
| Female | 36 | 36 | 72 |
| Male | 84 | 84 | 168 |
| Race/Ethnicity, Customized(Participants) | Opioid | Non-opioid | Total |
|---|---|---|---|
| White | 105 | 102 | 207 |
| Black | 7 | 11 | 18 |
| Other or Multiple | 7 | 6 | 13 |
| Missing | 1 | 1 | 2 |
| Region of Enrollment(Participants) | Opioid | Non-opioid | Total |
|---|---|---|---|
| United States | 120 | 120 | 240 |
| Brief Pain Inventory Interference(units on a scale) | Opioid | Non-opioid | Total |
|---|---|---|---|
| Mean | 5.4 ± 1.5 | 5.5 ± 2.0 | 5.5 ± 1.9 |
| Brief Pain Inventory Severity(units on a scale) | Opioid | Non-opioid | Total |
|---|---|---|---|
| Mean | 5.4 ± 1.5 | 5.4 ± 1.2 | 5.4 ± 1.4 |
| Primary Pain Location(Participants) | Opioid | Non-opioid | Total |
|---|---|---|---|
| Back pain | 78 | 78 | 156 |
| Hip/knee osteoarthritis pain | 42 | 42 | 84 |
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