A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of the XaraColl® Bupivacaine Implant (300 mg Bupivacaine Hydrochloride) After Open Laparotomy Hernioplasty
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 319
- 主要终点
- SPI24
研究概览
简要总结
This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled efficacy and safety study of postoperative pain in adults who are scheduled for unilateral inguinal hernioplasty via open laparotomy (tension-free technique).
Patients will assess their postoperative pain intensity (PI) using an 11-point numerical rating scale (NRS) from 0 hour through 72 hours postoperatively.
The expected maximum study duration for each patient will be up to 60 days, including a maximum 30-day screening period, the day of surgery and implantation, and a 30-day post implantation period including treatment and follow-up.
详细描述
This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in adults who are scheduled for unilateral inguinal hernioplasty via open laparotomy (tension-free technique). Patients will receive either 3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose; or 3 placebo-sponges.
Three test article sponges will be implanted according to the patient's blinded treatment assignment. Following surgery, patients will be transferred to a postanesthesia care unit (PACU) and/or other postoperative recovery area for observation where they may receive parenteral morphine as needed (rescue medication for breakthrough pain) and on request for pain control. Once patients can tolerate oral medication, they will commence a standardized oral analgesic regimen with additional PRN medication to manage breakthrough pain only when it occurs.
Patients will assess their postoperative pain intensity (PI) using an 11-point numerical rating scale (NRS) from 0 hour through 72 hours postoperatively.
Patients will be observed postoperatively for a minimum of 3 hours and may be discharged at any time following completion of their 3-hour vital sign and PI assessments. Patients will be contacted at approximately 6, 24 and 48 hours after implantation to ensure protocol compliance and to perform safety assessments (including AEs and concomitant medications). At 72 hours, patients will return to the clinic to perform their final PI assessment, complete a categorical assessment of their overall pain control, and for follow-up safety assessments. They will also be asked to record the incidence of any ongoing or subsequent AEs (and any associated treatment) through Day 7. Additional follow-up assessments for safety will be performed at postoperative Day 7 (telephone call) and Days 15 and 30 (clinic visits).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a planned (non-emergent) unilateral inguinal hernioplasty (open laparotomy, tension-free technique) to be performed according to standard surgical technique under general anesthesia. Repair of multiple hernias through a single incision is permitted provided only a single mesh will be used.
- •If female, is nonpregnant and nonlactating.
- •If female, is either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing 1 of the protocol specified medically-acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study:
- •Has the ability and willingness to comply with the study procedures and use of the eDiary.
- •Is willing to use only permitted medications throughout the study.
- •Is willing to use opioid analgesia.
- •Must be able to fluently speak and understand either English or Spanish and be able to provide meaningful written informed consent for the study.
排除标准
- •Has a known hypersensitivity to amide local anesthetics, morphine, acetaminophen or bovine products.
- •Is scheduled for bilateral inguinal hernioplasty or other significant concurrent surgical procedures per investigator discretion.
- •Has undergone major surgery within 3 months of the scheduled hernioplasty or plans to undergo another laparotomy procedure within 30 days postoperatively.
- •Has used any analgesic other than acetaminophen within 24 hours of surgery. Acetaminophen may be used on the day of surgery but is subject to preoperative restrictions for oral intake.
- •Has used aspirin or aspirin-containing products within 7 days of surgery. Aspirin at a dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the patient has been on a stable dose regimen for ≥ 30 days before Screening.
- •Has used systemic steroids, anticonvulsants, antiepileptics, antidepressants for the management of chronic pain, or monoamine oxidase inhibitors on a regular basis within 10 days of surgery.
- •Has used any opioid analgesic for an extended daily basis (30 - 60 mg oral morphine equivalent per day for 3 or more days a week) within 4 weeks before surgery. Patients who, in the investigator's opinion, may be developing opioid tolerance are also excluded.
- •Has any chronic painful condition (eg, fibromyalgia) or routinely uses pain medication other than acetaminophen (including nonsteroidal anti-inflammatory drugs [NSAIDs]) that, in the opinion of the investigator, may confound the assessment of pain associated with the hernioplasty.
- •Has a physical or mental condition that, in the opinion of the investigator, may confound the assessment of postoperative pain after hernioplasty.
- •Shows evidence of tolerance or physical dependency on opioid analgesics or sedative-hypnotic medications.
- •Has a urine drug screen that tests positive for drugs of abuse or misuse, including cannabinoids.
- •Has liver function test results greater than 3x the upper limit of normal or a history of cirrhosis.
- •Has any clinically significant unstable cardiac disease (eg, uncontrolled hypertension, clinically significant arrhythmia at baseline, or an implantable cardioverter-defibrillator [ICD])
- •Has any clinically significant unstable neurological, immunological, renal, or hematological disease (eg, uncontrolled diabetes or significantly abnormal laboratory findings), or any other condition that, in the opinion of the investigator, could compromise the patient's welfare, ability to communicate with the study staff or otherwise contraindicate study participation.
- •Has an open workman's compensation claim.
- •Has participated in a clinical trial (investigational or marketed product) within 30 days of surgery.
研究组 & 干预措施
XaraColl
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
干预措施: XaraColl (Drug)
Placebo
3 placebo implants
干预措施: Placebo (Other)
结局指标
主要结局
SPI24
时间窗: 0 to 24 hours
The primary efficacy variable (time-weighted sum of pain intensity from Time 0 through 24 hours \[SPI24\]) was compared once at a 2-sided 0.05 level. Therefore, no multiplicity adjustment was necessary for the primary efficacy analysis. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". Minimum value would be "0" and Maximum value would be 240. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI24 = ∑\[PI x (time t - time t-1)\], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
次要结局
- SPI48(0 to 48 hours)
- SPI72(0 to 72 hours)
- TOpA24(Time 0 through 24 hours)
- TOpA72(Time 0 through 72 hours)
- TOpA48(Time 0 through 48 hours)