A Depression and Opioid Pragmatic Trial in Pharmacogenetics
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,602
- 试验地点
- 20
- 主要终点
- 10 Day Silverman Integrated Analgesic Assessment (SIA) Score
研究概览
简要总结
This study is comprised of three separate pharmacogenetic trials grouped into a single protocol due to similarities in the intervention, the hypotheses, and the trial design. The three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial. Participants can enroll in only one of the three trials. All three trials were registered on ClinicalTrials.gov under NCT04445792. In July 2023 each of the three treatment trials was registered under a separate NCT# and NCT04445792 was converted to a screening record per recent guidance on master protocol research programs (MPRPs). This record is specific to the Acute Pain Trial within the ADOPT-PGx protocol.
The Acute Pain Trial is a prospective, multicenter, two arm randomized pragmatic trial. Participants meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic testing and genotype-guided post-surgical opioid therapy (Intervention arm) or standard care and pharmacogenetic testing after 6 months (Control arm). The investigators will test the hypothesis that pharmacogenetic testing and genotype guided pain management therapy improves pain control after surgery in participants who's body processes some pain medicines slower than normal.
详细描述
Pain and depression are conditions that impact substantial proportions of the US population. Finding safe and effective drug therapies for both conditions is challenging. In the case of treatment for acute and chronic pain, the challenge is finding effective therapy while minimizing adverse effects or opioid addiction (and the ensuing consequences). For depression, there are few clinically relevant predictors of successful treatment leading to multiple trials of inadequate therapy for some patients. Both opioid and antidepressant prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC).
This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic setting.
The rationale for examining a genotype-guided approach to acute and chronic pain management is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and hydrocodone and data from a pilot study supporting improved pain control in intermediate and poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline. Similarly, the rationale for examining a genotype-guided approach to depression medication therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19 oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials support the hypothesis of improved depression symptom control in a genotype-guided arm.
Study objectives:
Determine if a genotype-guided approach to acute post-surgical pain therapy leads to improved pain control compared to usual care, as defined by a decrease in the SIA score. Secondarily, The investigators will evaluate whether this approach leads to reduced use of DEA Schedule II opioids and reduced pain intensity.
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
- None
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute Pain Trial
- •Age ≥ 8 years
- •English speaking or Spanish speaking
- •Elective/planned surgery types with planned or anticipated to be treated with tramadol, hydrocodone, or codeine pain management at an enrolling site, which may include orthopedic surgeries (e.g. arthroplasty, spine, etc.), open abdominal surgery, or cardiothoracic surgery and others
- •Exclusion Criteria
- •Trial-wide:
- •Life expectancy less than 12 months
- •Are too cognitively impaired to provide informed consent and/or complete study protocol
- •Are institutionalized or too ill to participate (i.e. mental or nursing home facility or incarcerated)
- •Have a history of allogeneic stem cell transplant or liver transplant
- •People with prior clinical pharmacogenetic test results for genes relevant for the study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for depression) or already enrolled in an ADOPT PGx trial
- •Acute Pain Trial
- •Undergoing a laparoscopic surgery
- •Receiving chronic opioid therapy, defined as use of opioids on most days for >3 months
排除标准
- 未提供
结局指标
主要结局
10 Day Silverman Integrated Analgesic Assessment (SIA) Score
时间窗: Day of surgery (baseline) to 10 days post surgery
A composite measure of pain and opioid usage, the Silverman Integrated Analgesic Assessment (SIA) score, at 10 days post-surgery in participants who have a genotypic or pheno-converted CYP2D6 activity score ≤ 0.75. The SIA has a total score range of -200 to 200, where a higher score corresponds with higher pain and opioid use.
次要结局
- 10 Day Pain Intensity as Measured by the PROMIS Numeric Pain Rating Scale(10 days post-surgery)
- Post-surgery Opioid Usage, Measured in Milligrams of Morphine Equivalents (MME) Per Day(Day of surgery (baseline) to 10 days post surgery)
- 3 Month Prescription Pain Medication Misuse(3 months post surgery)
- 1 Month PROMIS Mobility Score(1 month post surgery)
- Number of Participants With Opioid Persistence(3-6 months post-surgery, assessed at 6 months)
- Participants With Drug-Gene Concordance(Within 10 days post-surgery)