Relieving Acute Pain (RAP): A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Pain Self-reports
研究概览
简要总结
The United States (US) faces a crisis of pain management. According to the 2012 National Health Interview Survey, almost 50 million adults in the US reported having significant chronic or severe pain (Nahin 2015). Doctors in the US still prescribe opioids across the board for pain despite a growing recognition of an epidemic of opioid overdose and use disorder. Few solutions have been successfully proposed and implemented. Placebos represent a novel and potentially fruitful means of addressing this issue. However, clinicians often use placebos deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Recently, we reviewed a database of placebo studies including 22 studies in both animals and humans hinting of evidence that placebos may work as a dose extender of active painkillers. Placebos given after repeated administration of active treatments can acquire medication-like effects based on learning mechanisms.
Here, we will test if dose-extending placebos are effective in relieving clinical acute pain in opioid patients with traumatic pain. Patients will be randomized to three arms. Arm 1 will be a Full Dose (FD) group, which will receive all NSAIDs as described in the Guidelines for NSAID use in Orthopedic Patients and Oxycodone (5mg). Arm 2 will be a Partial Reinforcement (PR) group, which will receive NSAIDs, Oxycodone (5mg), and placebos to reach a 50% reduction of the total intake of opioids. Finally, Arm 3 will be a Control (C) group receiving NSAIDs and placebos. Patients will be assigned to one of three arms according to a 1:1:1 schedule of randomization. Study IDs will be generated by the pharmacy and blinding will occur by ensuring that oxycodone and placebos look, smell, and taste identical. Rescue therapy will be provided as needed. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated.
详细描述
Overview:
We will screen 500 patients from the Shock Trauma Center to recruit a total of 159 (53 per arm) to participate in a pilot study aimed at reducing use of opioids. Participants will meet all of the eligibility criteria and none of the exclusion criteria. After enrollment, participants will be blindly allocated to one of three randomization arms by means of de-identified Study IDs corresponding to treatment arms. Study IDs will be generated by the pharmacy and blinding will be ensured by creating study drugs that look, smell, and taste identical. The pharmacy will create and dispense identical study drugs in terms of appearance, smell, and taste. Only the blinding coordinator will know the identity of patients in each treatment arm. Arm 1 will be a Full Dose (FD) group, which will receive Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), dosed in accordance with the University of Maryland Shock Trauma Center (STC) Guidelines for NSAIDs and Oxycodone (5mg). Arm 2 will be a Partial Reinforcement (PR) group, which will receive NSAIDs, Oxycodone (5mg), and placebos to reach a 50% reduction of the total intake of opioids. Finally, Arm 3 will be a Control (C) group receiving NSAIDs and placebos. Patients will be assigned to one of these three arms according to a 1:1:1 schedule of randomization. The patient will start receiving study medication as part of his or her pain management as soon as possible after admission to the hospital and enrollment in the study (ideally as their first dose of pain-management medication). Rescue therapy will be provided as needed.
All enrolled patients will receive an Adult Pain Management Service (APMS) consult. APMS will work with the study and clinical teams to ensure that all treatment protocols are met, and be available to address any issues that may arise. The APMS provider will work with the primary service to determine the most effective NSAID as described in their guidelines.
Other than the study medication (Oxycodone and placebo), all participants will be treated in accordance with the current standard of care at the University of Maryland Shock Trauma Center. This includes intravenous Toradol every 8 hours for 24 hours followed by oral NSAIDs round the clock until pain is minimal. The timing of administration will be the same for participants in all three arms - they will receive their arm's treatment (Oxycodone, Oxycodone alternating with placebo, or no additional medication beyond standard of care NSAIDs) round the clock for the first 24 hours followed by every hours for the remainder of hospitalization. All patients will receive intravenous Dilaudid every hour for rescue or break through pain. In addition, all patients will be discharged on Oxycodone tablets (5mg) every 3 hours as needed.
In Arm 2, the first four doses of study drug will be Oxycodone (5mg) to condition them to its effects. Afterwards, they will receive alternating Oxycodone (5mg) and placebo according to one of four repeating sequences. During data analysis, we will test whether the sequence of administration has an effect on outcomes. Participants in Arm 2 will never receive more than 2 doses of placebo in a row. This administration schedule will be repeated for the remainder of hospitalization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Oxycodone and Placebo will be identical in terms of appearance, taste, and smell so as to keep the investigators, care providers, and participants blind to their treatment allocation. Oxycodone and placebo oral suspensions will be manufactured and dispensed by the pharmacy at University of Maryland Medical Center. All research personnel, aside from the pharmacists and team members responsible for final review and write-up of the study, will be blinded to participants' treatment groups. For participants in the Partial Reduction group (Arm 2), the pharmacy will dispense the study drug such that participants in Arm 2 will receive four doses of Oxycodone (5mg) followed by one of four repeating schedules of administration alternating between Oxycodone (5mg) and placebo.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65
- •Admission to The Shock Trauma Center within 72 hrs
- •Any trauma requiring inpatient opioid medication
- •Plan by primary service to follow the Shock Trauma Guidelines for Acute Pain in Orthopedic Injury
- •Predicted length of stay greater than or equal to 2 days
排除标准
- •Non English speaking
- •Spine cord injury
- •Severe Traumatic brain injury (based on a Glascow Coma Scale of 8 or less)
- •Patient-controlled analgesia
- •Admission Creatinine > 1.4
- •History of chronic kidney disease
- •Heroin use in the 3 months prior to admission (patient self-report)
- •Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, mania, autism) and /or psychiatric condition leading to treatment and/or hospitalization within the last 1 year.
- •Positive toxicology screen for methadone not prescribed during current hospitalization
- •Pregnancy or breast feeding
- •Contraindication to NSAIDs, including high risk of bleeding or known severe coronary artery disease
- •Injuries deemed non survival.
研究组 & 干预措施
PR (Partial Reinforcement)
Participants in this group will receive NSAIDs, Oxycodone (5mg), and placebo pills to reach a 50% reduction of the total intake of opioids.
干预措施: Ketorolac (Drug)
PR (Partial Reinforcement)
Participants in this group will receive NSAIDs, Oxycodone (5mg), and placebo pills to reach a 50% reduction of the total intake of opioids.
干预措施: Oxycodone (Drug)
Full Dose (FD)
Participants in the FD arm will receive NSAIDs and Oxycodone (5mg).dosed in accordance with the Guidelines for Use from University of Maryland Shock Trauma Center.
干预措施: Ketorolac (Drug)
C (Control)
Participants in this group will receive NSAIDs and placebo pills
干预措施: Placebo (Other)
PR (Partial Reinforcement)
Participants in this group will receive NSAIDs, Oxycodone (5mg), and placebo pills to reach a 50% reduction of the total intake of opioids.
干预措施: Placebo (Other)
Full Dose (FD)
Participants in the FD arm will receive NSAIDs and Oxycodone (5mg).dosed in accordance with the Guidelines for Use from University of Maryland Shock Trauma Center.
干预措施: Oxycodone (Drug)
C (Control)
Participants in this group will receive NSAIDs and placebo pills
干预措施: Ketorolac (Drug)
结局指标
主要结局
Pain Self-reports
时间窗: Day 1-7, Week 2, Months 1, 3 and 6
Collected on a visual analogue scale, with 0 being "no pain" and 100 being "maximum pain tolerable"
次要结局
未报告次要终点
研究者
Luana Colloca
Associate Professor
University of Maryland, Baltimore