Clinical trial NCT03454555: Integrated Services for Pain: Interventions to Reduce Pain Effectively
Official title: Integrated Health Services to Reduce Opioid Use While Managing Chronic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Pain
Keywords: Pragmatic Clinical Trial
Comparative Effectiveness Research
Analgesics, Opioid
Decision Making, Shared
Motivational Interviewing
Cognitive Therapy
Patient Reported Outcome Measures
Chronic Pain
Pain
Neurologic Manifestations
Lead sponsor: RTI International
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: University of North Carolina Health Care System
name: Duke Health
name: Vanderbilt University Medical Center
First posted: 2018-03-06
Enrollment: 526
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to one of two intervention arms for the duration of the study. The study will use real-time 1:1 ratio randomization to limit participant loss prior to treatment. Eligible patients will be randomized using a stratified, permuted-block design, as this constrained randomization approach ensures balance between treatment groups within each of the 3 clinical institutions (our only stratification factor) at the completion of each block. Consequently, throughout the trial, the intervention arms are expected to have approximately equal sample sizes both within an institution and across the study.
Primary purpose: TREATMENT

Brief summary: What is the research about?

Long-term pain -or pain that lasts for months or years-is one of the most common health problems in the United States. Clinicians often treat long-term pain with opioids. Opioids can help ease pain in the short term, but evidence does not support their effectiveness in the long term. For some people, long-term opioid use can lead to addiction and overdose. People need effective options and support to help improve their function and enjoy life as much as possible.

What is the research team doing?

This study that compared two programs for helping people living with long-term pain to improve their function while managing their pain. People with long-term pain who had been taking opioid medicines for 3 or more months could be in the study. This study was done at primary care and pain care clinics at 3 health systems in North Carolina and Tennessee.

The study team assigned people by chance to one of two study programs: (1) Shared Decision Making (SDM) or (2) Cognitive Behavioral Therapy and Motivational Interviewing (CBT+MI). Both programs went by clinical guidelines for opioid prescribing.

In the SDM program, the patient and clinician worked together to make decisions that were best for the patient. In the CBT+MI program, the patient learned strategies to better cope with chronic pain.

The study team compared the two programs by looking at changes in opioid dose, physical functioning, and pain interference over time. They collected information on prescribed opioid dose from electronic health records. People did surveys at the start of the study and at 6 and 12 months.

Study data collection is over, and the study team is analyzing data. Results are forthcoming.

The study team worked with an advisory group that included patients, advocates, clinicians, and pain experts. The advisory group met with the study team two to three times per year to provide input on the study.

Detailed description: Rationale:

Up to one-third of Americans suffer from chronic non-cancer pain (CNCP). Opioids are often used to treat CNCP. Once on chronic opioid therapy (COT) individuals often continue with this class of medication for years. Evidence for the effectiveness of COT to treat CNCP is limited, exposing individuals to known risks. Modified or novel pharmacological and nonpharmacological strategies are needed to improve pain management and promote informed decision making regarding possible opioid dose reduction.

Study Design and Approach:

This is a large-scale, pragmatic randomized controlled trial implementing pharmacotherapy guidelines and behavioral interventions in real-world settings. A pragmatic trial is a study designed to evaluate the effectiveness of interventions in broad patient groups in routine clinical practice. This differs from an explanatory trial, which is designed to evaluate efficacy under ideal conditions.

In this trial, the researchers will examine the comparative effectiveness of two approaches to reducing opioid dose for CNCP who are on COT: shared decision making (SDM) and guideline-concordant pharmacotherapy (SDM Arm) versus motivational interviewing plus cognitive behavioral therapy for chronic pain (MI+CBT-CP) and guideline-concordant pharmacotherapy (MI+CBT-CP Arm).

This project will evaluate two nonpharmacologic approaches to pain management and opioid reduction in primary care and specialty pain clinics. The approaches are designed to educate medical care providers, educate patients currently being treated for CNCP, help patients address pain and pain coping skills, and enhance patient motivation to reduce or discontinue opioid use. This study will determine the feasibility, effectiveness and potential scalability of these interventions in reducing opioid use in patients who are using ≥ 20 morphine equivalent doses (MED). The study will also assess patient acceptability of the interventions including involvement in their implementation and willingness to incur out-of-pocket costs associated with the visits.

Objectives:

To conduct a multisite pragmatic trial of two active interventions: SDM as compared with MI+CBT-CP.

Primary Objective:

\* To assess if the interventions result in opioid dose reduction and to compare their effectiveness.

Secondary Objectives:

* To examine the impact of the interventions on physical function.
* To examine the impact of the interventions on pain interference.

Timeline:

The project commenced in February 2018. Participant recruitment occurred from June 2019 to March 2022. Delivery of the intervention occurred on a rolling basis through March 2023.

Recruitment, Screening, Enrollment, and Randomization:

The study enrolled 526 participants from primary care and pain clinics at three medical centers in North Carolina and Tennessee. The researchers identified patients who are potentially eligible through electronic health records and contacted these patients with an invitation to participate. A Research Coordinator contacted patients to complete screening, enrollment, and randomization. The researchers randomized enrolled participants to either the SDM Arm or MI+CBT-CP Arm of the intervention.

Interventions:

In the SDM arm, patients and clinicians engaged in SDM. In the MI+CBT-CP Arm, patients participated in MI+CBT-CP. Patients in both study arms received guideline-concordant pharmacotherapy treatment, based on clinical guidelines for opioid therapy for CNCP.

Data Collection:

The researchers employed a comprehensive, multi-mode data collection method that included collecting patient-reported outcomes through Web-based and phone-based surveys and leveraging existing harmonized electronic health record (EHR) data. The researchers will use validated measures to measure the impact of the interventions.

The researchers will assess the primary outcome, change in opioid dose from baseline, using EHR data at 6 timepoints: 3 months, 6 months, 9 months, 12 months, 15 months, and 18 months. Change from baseline in average daily opioid dose will be measured as prescribed morphine equivalent dose (MED). The researchers will measure the secondary outcomes, physical functioning and pain interference, via participant survey at three timepoints: baseline, 6 months, and 12 months.

Data Analysis and Reporting:

In a large pragmatic trial such as the one planned, the probability is small that the groups will have imbalance by age, sex, health behaviors, or other measured or unmeasured possible confounding factors. Nevertheless, the researchers will assess whether randomization has successfully created comparable groups by descriptively comparing their baseline demographic characteristics and potential confounders, including baseline pain score, comorbidities, opioid dosage, and number and type of CNCP conditions.

The researchers will evaluate clinical outcomes and patient-reported outcomes using cross-sectional and longitudinal intent-to-treat analyses. These analyses will use mixed effects models to compare opioid dose between the two study arms over an 18-month period. The researchers also will explore differences in the intervention effect according to participant characteristics, such as age, sex, baseline pain level, baseline opioid dose, and the presence of physical comorbidities, mental health comorbidities, or history of substance abuse. Qualitative research methods have been used to obtain participant input on their experiences.

Eligibility criteria: Inclusion Criteria:

* Aged 18 to 85 years
* History of chronic non-cancer pain (CNCP)
* Receiving high-dose chronic opioid therapy for CNCP as evidenced by current or most recent prescription of an average daily morphine-equivalent dose of 20 mg or greater
* Receiving care at a participating clinic from a participating provider, as evidenced by at least 1 in-person visit within the past 12 months.

Exclusion Criteria:

* Not meeting the above inclusion criteria
* Opioid use is for pain directly related to an active cancer diagnosis
* Opioid use is for maintenance treatment of an opioid use disorder
* Suicide attempt within the past 3 years
* Active suicidal ideation
* Currently receiving Cognitive-Behavioral Therapy (CBT)
* Non-English speaking
* Other reason at the discretion of the investigator

Primary outcomes:
measure: Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 3
timeFrame: Baseline and Month 3
measure: Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 6
timeFrame: Baseline and Month 6
measure: Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 9
timeFrame: Baseline and Month 9
measure: Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 12
timeFrame: Baseline and Month 12
measure: Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 15
timeFrame: Baseline and Month 15
measure: Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 18
timeFrame: Baseline and Month 18
measure: Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 3
timeFrame: Baseline and Month 3
measure: Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 6
timeFrame: Baseline and Month 6
measure: Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 9
timeFrame: Baseline and Month 9
measure: Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 12
timeFrame: Baseline and Month 12
measure: Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 15
timeFrame: Baseline and Month 15
measure: Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 18
timeFrame: Baseline and Month 18
measure: Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 3
timeFrame: Baseline and Month 3
measure: Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 9
timeFrame: Baseline and Month 9
measure: Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 12
timeFrame: Baseline and Month 12
measure: Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 15
timeFrame: Baseline and Month 15
measure: Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 18
timeFrame: Baseline and Month 18
Secondary outcomes:
measure: Change from Baseline in Pain Interference on the 8-item Patient-Reported Outcomes Measurement Information System - Pain Interference (PROMIS-PI) at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Pain Interference on the 8-item Patient-Reported Outcomes Measurement Information System - Pain Interference (PROMIS-PI) at Month 12
timeFrame: Baseline and Month 12
measure: Change from Baseline in Physical Functioning on the 8-item Patient-Reported Outcomes Measurement Information System - Physical Functioning (PROMIS-PF) at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Physical Functioning on the 8-item Patient-Reported Outcomes Measurement Information System - Physical Functioning (PROMIS-PF) at Month 12
timeFrame: Baseline and Month 12
Other outcomes:
measure: Change from Baseline in Pain Intensity on the 3-item Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Pain Intensity on the 3-item Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity at Month 12
timeFrame: Baseline and Month 12
measure: Change from Baseline in Anxiety on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress - Anxiety at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Anxiety on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress - Anxiety at Month 12
timeFrame: Baseline and Month 12
measure: Change from Baseline in Depression on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Depression at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Depression on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Depression at Month 12
timeFrame: Baseline and Month 12
measure: Change from Baseline in Pain Severity on the 4-item Brief Pain Inventory (BPI) Pain Severity at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Pain Severity on the 4-item Brief Pain Inventory (BPI) Pain Severity at Month 12
timeFrame: Baseline and Month 12
measure: Change from Baseline in Pain Interference on the 7-item Brief Pain Inventory (BPI) Pain Interference at Month 6
timeFrame: Baseline and Month 6
measure: Change from Baseline in Pain Interference on the 7-item Brief Pain Inventory (BPI) Pain Interference at Month 12
timeFrame: Baseline and Month 12
measure: Discontinuation of Opioid Medications at Month 12
timeFrame: Month 12
measure: Intent to Taper at Baseline
timeFrame: Baseline
measure: Intent to Taper at Month 6
timeFrame: Month 6
measure: Intent to Taper at Month 12
timeFrame: Month 12
measure: Relative opioid use self-report at Month 6
timeFrame: Month 6
measure: Relative opioid use self-report at Month 12
timeFrame: Month 12
measure: Protocol-Specified Adverse Events (AEs) through Month 12
timeFrame: Baseline Through Month 12
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Health Care System
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: RTI International
name: Lauren McCormack, PhD,MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agency for Healthcare Research and Quality. (2017, February). The SHARE Approach. Retrieved from http://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html
citation: Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, Blazina I, Dana T, Bougatsos C, Turner J. The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain. Evid Rep Technol Assess (Full Rep). 2014 Sep;(218):1-219. doi: 10.23970/AHRQEPCERTA218.
citation: Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK91497/
citation: Martin BC, Fan MY, Edlund MJ, Devries A, Braden JB, Sullivan MD. Long-term chronic opioid therapy discontinuation rates from the TROUP study. J Gen Intern Med. 2011 Dec;26(12):1450-7. doi: 10.1007/s11606-011-1771-0. Epub 2011 Jul 13.
citation: Monticone M, Ambrosini E, Cedraschi C, Rocca B, Fiorentini R, Restelli M, Gianola S, Ferrante S, Zanoli G, Moja L. Cognitive-behavioral Treatment for Subacute and Chronic Neck Pain: A Cochrane Review. Spine (Phila Pa 1976). 2015 Oct 1;40(19):1495-504. doi: 10.1097/BRS.0000000000001052.
citation: Vanderlip ER, Sullivan MD, Edlund MJ, Martin BC, Fortney J, Austen M, Williams JS, Hudson T. National study of discontinuation of long-term opioid therapy among veterans. Pain. 2014 Dec;155(12):2673-2679. doi: 10.1016/j.pain.2014.09.034. Epub 2014 Sep 30.
citation: Edlund MJ, Thomas SM, Wagner LK, Thompson JE, Wu LT, Dolor RJ, Chelminski PR, Ives TJ, Archer KR, Dewey CM, Sullivan MD, McCormack LA; INSPIRE Study Team. Design of a Multicenter Randomized Controlled Trial comparing the effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for voluntary opioid tapering: The INSPIRE study protocol. Contemp Clin Trials. 2024 Feb;137:107410. doi: 10.1016/j.cct.2023.107410. Epub 2023 Dec 12.