NMDA Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicentre Pilot Study
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Follow-up
研究概览
简要总结
The objective of the PAIN-STOP trial is to assess the feasibility of a larger randomized controlled trial (RCT) evaluating NMDA antagonists and IV steroids, as compared to placebo, in decreasing the chances of clinically significant persistent post-surgical pain (PPSP) after video assisted thoracoscopic surgeries (VATS). This is a multi-centre randomized, controlled clinical trial with a 2 x 2 factorial design. The pilot phase of the trial will recruit 48 patients and follow them for 3 months. Patients will be randomized to one of four groups: 1) NMDA active + Steroid placebo; 2) Steroid active + NMDA placebo; 3) NMDA active + Steroid active; 4) NMDA placebo + Steroid placebo.
详细描述
Persistent Post-Surgical Pain (PPSP) after Video Assisted Thoracic Surgery (VATS) lobectomy procedures is an important health problem for which there is no effective method of prevention. NMDA antagonists and steroids can modify pain signaling-sensitization pathways, and inflammatory-immune pathways, and hence can potentially prevent the development of PPSP. These agents have been safely used in thoracic surgeries to obtain many perioperative benefits, without increasing the harmful effects. Since these agents act by different biological mechanisms, it is appropriate to study their effects in a factorial design to increase the trial efficiency. Before conducting a large multicenter trial, we propose to establish the feasibility by carrying out this feasibility trial.
The objective of the PAIN-STOP trial is to assess the feasibility of a larger randomized controlled trial (RCT) evaluating NMDA antagonists and IV steroids, as compared to placebo, in decreasing the chances of clinically significant persistent post-surgical pain (PPSP) after video assisted thoracoscopic surgeries (VATS). This is a multi-centre randomized, controlled clinical trial with a 2 x 2 factorial design. The pilot phase of the trial will recruit 48 patients and follow them for 3 months. Patients will be randomized to one of four groups: 1) NMDA active + Steroid placebo; 2) Steroid active + NMDA placebo; 3) NMDA active + Steroid active; 4) NMDA placebo + Steroid placebo. Follow-up visit will be conducted in hospital; day 8 and month 2 by a phone call; and in person follow-up visits at 30 days and 3 months post-randomization; for patients who cannot attend in person, a telephone follow up will be done.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients, health care providers, data collectors, outcome adjudicators, and Investigators (e.g., Steering Committee Members) will all be blind to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-75 years of age,
- •Planned elective VATS pulmonary lobectomy,
- •Provide written informed consent to participate.
排除标准
- •Current pain on the same side of the chest of moderate to severe intensity (>3/10 in 0-10 numerical rating scale (NRS) - where 0=no pain, 10=maximum pain),
- •Known intracranial mass or cerebral aneurysm or raised intraocular pressure,
- •Severe renal impairment (creatinine clearance based GFR of <30ml/min),
- •Allergies to one or more of the study medications,
- •Steroid treatment > 10mg/day of Prednisolone or its equivalent for > 3 weeks within the last 3 months,
- •History of schizophrenia or bipolar disorder,
- •History of drug addiction (prescription or non-prescription drug addiction diagnosed by a physician, excluding alcohol),
- •Current diagnosis of Cushing's syndrome,
- •Pregnancy,
- •Previous participation in the PAIN-STOP trial.
研究组 & 干预措施
NMDA active + Steroid placebo
NMDA active: ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID [first week]; 10 mg BID [following three weeks]).
Steroid placebo: two doses of normal saline; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: NMDA active (Drug)
NMDA active + Steroid placebo
NMDA active: ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID [first week]; 10 mg BID [following three weeks]).
Steroid placebo: two doses of normal saline; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: Steroid placebo (Drug)
Steroid active + NMDA placebo
NMDA placebo: normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (one capsule BID [first week]; one capsule BID [following three weeks]).
Steroid active: two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: Steroid active (Drug)
Steroid active + NMDA placebo
NMDA placebo: normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (one capsule BID [first week]; one capsule BID [following three weeks]).
Steroid active: two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: NMDA placebo (Drug)
NMDA active + Steroid active
NMDA active: ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID [first week]; 10 mg BID [following three weeks]).
Steroid active: two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: NMDA active (Drug)
NMDA active + Steroid active
NMDA active: ketamine (0.5 mg/kg IV bolus pre-incision and 0.1 mg/kg/hr infusion postoperatively up to 24 hours) and oral memantine (5 mg BID [first week]; 10 mg BID [following three weeks]).
Steroid active: two doses of dexamethasone; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: Steroid active (Drug)
NMDA placebo + Steroid placebo
NMDA placebo: normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (one capsule BID [first week]; one capsule BID [following three weeks]).
Steroid placebo: two doses of normal saline; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: NMDA placebo (Drug)
NMDA placebo + Steroid placebo
NMDA placebo: normal saline (IV bolus pre-incision and infusion postoperatively up to 24 hours) and oral matching placebo to memantine (one capsule BID [first week]; one capsule BID [following three weeks]).
Steroid placebo: two doses of normal saline; 25 mg given prior to starting surgery and 25 mg given on the morning of second postoperative day.
干预措施: Steroid placebo (Drug)
结局指标
主要结局
Follow-up
时间窗: 9 months
Ability to obtain follow-up in \>90% of enrolled patients, at three months.
Recruitment
时间窗: 6 months
Ability to recruit at least 4 patients per month per site, and complete the recruitment over a 6-month period.
次要结局
- NRS - Incidence of PPSP(3 months)
- Use of narcotic analgesic medication(3 months)
- Difference in Quality of Life(3 months)
- Thoracic surgery specific activity limitations(3 months)
- Change in global health status(3 months)
- NRS - Incidence of PPSP with movement evoked(3 months)
- Presence of NP(3 months)
- BPI score(3 months)
- Rate of change of postoperative pain intensity(3 months)