JAMA | Original Investigation
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
Erin E. Krebs, MD, MPH; Amy Gravely, MA; Sean Nugent, BA; Agnes C. Jensen, MPH; Beth DeRonne, PharmD; Elizabeth S. Goldsmith, MD, MS;
Kurt Kroenke, MD; Matthew J. Bair; Siamak Noorbaloochi, PhD
IMPORTANCE Limited evidence is available regarding long-term outcomes of opioids
compared with nonopioid medications for chronic pain.
OBJECTIVE To compare opioid vs nonopioid medications over 12 months on pain-related
function, pain intensity, and adverse effects.
DESIGN, SETTING, AND PARTICIPANTS Pragmatic, 12-month, randomized trial with masked
outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from
June 2013 through December 2015; follow-up was completed December 2016. Eligible patients
had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use.
Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized.
INTERVENTIONS Both interventions (opioid and nonopioid medication therapy) followed a
treat-to-target strategy aiming for improved pain and function. Each intervention had its own
prescribing strategy that included multiple medication options in 3 steps. In the opioid group,
the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen.
For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal
anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned
treatment group according to individual patient response.
MAIN OUTCOMES AND MEASURES The primary outcome was pain-related function (Brief Pain
Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain
intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function
or pain intensity), a 1-point improvement was clinically important. The primary adverse
outcome was medication-related symptoms (patient-reported checklist; range, 0-19).
RESULTS Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234
(97.5%) completed the trial. Groups did not significantly differ on pain-related function over
12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and
3.3 for the nonopioid group (difference, 0.1 [95% CI, −0.5 to 0.7]). Pain intensity was
significantly better in the nonopioid group ove...
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