Percutaneous Cryoneurolysis: A Single-administration, Non-opioid, Non-addictive, Multiple-month Analgesic for Thoracic Trauma Free of Systemic Side Effects
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 120
- 试验地点
- 8
- 主要终点
- Opioid consumption during first 2 post-intervention months
研究概览
简要总结
Thoracic trauma frequently involve rib fractures which can be very painful for 2-3 months. Unfortunately, pain is not simply a "symptom" of the injuries, but a significant cause of additional medical problems: pain causes people to breath and cough less deeply/often which increases the risk of collapsing little parts of the lung. These collapsed areas often lead to complications which can increase the risk of death. In addition, the higher the amount of pain in the weeks following the fracture, the higher the risk of developing persistent, chronic pain that can last indefinitely. So, providing excellent pain control is very important for a variety of reasons. Various nerve blocks can greatly decrease pain, but even the longest acting are measured in hours or days, and not the weeks and months for which rib fracture pain can last. Therefore, opioids-"narcotics"-are the most common pain control method provided to patients; but they frequently do not provide enough pain control, have undesirable side effects like nausea and vomiting, and are sometimes misused which can lead to addiction or overdose.
A prolonged nerve block lasting multiple months from a single treatment may be provided by freezing the nerve using a process called "cryoneurolysis". With cryoneurolysis and ultrasound machines, a very small "probe" may be placed through anesthetized skin and guided to the target nerve to allow freezing. The procedure takes about 5 minutes for each nerve, involves little discomfort, has no side effects, and cannot be misused or addictive. After 2-3 months, the nerve returns to normal functioning. The investigators have completed a small study suggesting that a single cryoneurolysis treatment provides potent short- and long-term pain relief following thoracic trauma with rib fractures. The ultimate objective of the proposed research is to determine if percutaneous cryoneurolysis is an effective non-opioid, single-application treatment for pain following traumatic rib fracture.
The current project is a pragmatic, multicenter, randomized, triple-masked (investigators, participants, statisticians), sham/placebo-controlled, parallel-arm, human-subjects, post-market clinical trial to determine if cryoneurolysis is an effective non-opioid treatment for pain following traumatic rib fractures.
详细描述
The investigators propose a pragmatic, multicenter, randomized, triple-masked (investigators, participants, statisticians), sham/placebo-controlled, parallel-arm, human-subjects clinical trial to determine if cryoneurolysis is an effective non-opioid treatment for pain following traumatic rib fractures. Participants will be recruited at 6 enrolling centers:
- Brigham and Women's Hospital, Boston, Massachusetts
- University of Texas, Houston, Houston, Texas
- Massachusetts General Hospital, Boston, Massachusetts
- University of California, San Diego, San Diego, California
- Walter Reed National Military Medical Center, Bethesda, Maryland
For individuals of childbearing potential, a sample of urine will be collected before any study interventions to confirm a non-pregnant state [this is standard for any trauma regardless of study participation]. Participants will have a peripheral intravenous (IV) catheter inserted, standard noninvasive monitors applied (blood pressure cuff, pulse oximeter, 5-lead ECG), and oxygen administered via a facemask. Midazolam and fentanyl (IV) will be titrated for patient comfort as needed throughout the procedure, while ensuring that patients remain responsive to verbal cues.
Treatment group allocation (randomization). Participants will be allocated to one of two possible treatments groups:
- Cryoneurolysis
- Local anesthetic nerve block (Control)
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)
盲法说明
All investigators, participants, and clinical staff will be masked to treatment group assignment, with the only exception being the unmasked individual who performs the procedure (and will not have subsequent contact with the participant).
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
- •Adult patients of at least 18 years of age
- •A total of 1-6 traumatic rib fractures confirmed by imaging at least 3 cm distal to the costotransverse joint sustained within the previous 60 h (bilateral fractures are acceptable, but the total of the two sides combined must not exceed 6 fractures)
- •Pain in the fractured rib(s) region rated at least moderate (5 on the 0-10 Numeric Rating Scale) at rest
- •Undergoing a single-injection peripheral nerve block to treat the pain of the rib fracture(s)
排除标准
- •Anticoagulation or bleeding disorder: introduction of the percutaneous cryoneurolysis probe has a risk of hemorrhage similar to the percutaneous insertion of a similar gauge needle; but an anticoagulated state will increase the risk of hemorrhage (aspirin in doses for cardiothoracic/stroke prophylaxis [≤ 325 mg] are acceptable).
- •Infection at the site of probe introduction: percutaneous insertion of the probe through a cutaneous infection would bring an unacceptable risk of introducing the infection to deeper tissues.
- •Pulmonary disease or injury requiring supplemental oxygen: one theoretical risk of cryoneurolysis is a unilateral pneumothorax (not reported) which could result in a compromised pulmonary state for patients who require supplemental oxygen at baseline.
- •Neurologic deficit of the intercostal nerves of the fractured ribs: cryoneurolysis is theoretically a potent analgesic, but it does not "heal" injured nerves. Therefore, nerve deficits-either pre-existing or due to the trauma-will confound the analgesia-related results.
- •Possessing any contraindication to decreased temperature such as cryoglobulinemia, cryofibrinogenemia, cold urticaria paroxysmal cold hemoglobinuria, or Raynaud's disease: the decreased temperature accompanying cryoneurolysis could result in local tissue/vascular compromise for patients with any of these cold-triggered syndromes/diseases.
- •Insulin-dependent diabetes: laboratory studies have demonstrated impaired nerve regeneration in diabetic animals, and diabetes in patients can lead to impaired regeneration of axons and recovery following investigational nerve injury as well as focal neuropathies such as ulnar neuropathy and carpal tunnel syndrome. Whether these findings are applicable to cryoneurolysis in patients with diabetes remains unknown, but we prefer to error on the side of caution for study participants.
- •Chronic opioid use (daily use within the 2 weeks prior to the fracture and duration of use > 4 weeks): individuals using opioids on a chronic basis will continue their baseline opioid requirements following the traumatic event. This will confound the analgesic results of the study.
- •Inability to use an incentive spirometer: One of the Specific Aims involves improving functioning by decreasing pain using cryoneurolysis, and this will be evaluated using an incentive spirometer. For this reason, patients who are intubated or for whom there is anticipation of intubation will be excluded.
- •Any injury outside of the fractured rib(s) which results in moderate pain (NRS > 3) and/or anticipated to require opioid analgesics: such injuries would confound the results for the intervention under investigation.
- •An existing or planned continuous neuraxial or peripheral nerve block.
- •Fracture of the 1st rib on either side
- •Flail chest (3 or more adjacent ribs, each fractured in more than one location to create a free-floating segment)
- •Any degree of decreased mental capacity as determined by the surgical service or investigators.
- •Inability to contact the investigators during the treatment period, and vice versa (e.g., lack of telephone access).
- •Incarceration
- •Number and location of fractures would require more than 10 intercostal nerves to be treated with cryoneurolysis
结局指标
主要结局
Opioid consumption during first 2 post-intervention months
时间窗: Post-intervention months 1 and 2, collected on days 1, 2, 3, 7, 14, 21, 30, 45 and 60; at each collection time point, opioid use for the previous 24 hours will be recorded
Cumulative opioid dose measured in oral oxycodone equivalents following intervention for 9 specific 24-hour time points over the first 2 months following surgery. With 9 time points (post-intervention days 1, 2, 3, 7, 14, 21, 30, 45 and 60), this will encompass 216 hours in total of the first 2 post-intervention months. In order to claim that percutaneous cryoneurolysis is superior to usual and customary analgesia, at least one of Outcomes 1 and 2 must be superior while the other at least noninferior.
Average pain during first 2 post-intervention months
时间窗: Post-intervention months 1 and 2, collected on days 1, 2, 3, 7, 14, 21, 30, 45 and 60; at each collection time point, the "average" pain score for the previous 24 hours will be recorded
The area under the curve for the "average" daily pain scores over the first 2 post-intervention months. At 9 specific time points the "average" pain score following the intervention will be measured using the numeric rating scale. This is a 0-10 Likert scale measuring pain level with 0=no pain and 10= worst imaginable pain. In order to claim that percutaneous cryoneurolysis is superior to usual and customary analgesia, at least one of Outcomes 1 and 2 must be superior while the other at least noninferior.
次要结局
- Average pain(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Brief Pain Inventory, short form (interference subscale)(Collected on post-intervention days 3, 7, 14, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Opioid consumption(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Least/lowest/minimal pain(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Current pain(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Number of participants with pulmonary complications(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Worst/maximum pain(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Masking assessment(Post-intervention Day 7)
- Depression screening with the Patient Health Questionnaire (PHQ-2)(Post-intervention Months 3, 6, 9, and 12)
- Nociceptive vs neuropathic pain estimation(Collected on post-intervention months 6, 9 and 12)
- Days hospitalized(Post-intervention Days 0-14)
- First 2 months area under the curve of the Brief Pain Inventory, short form (interference subscale)(Collected on post-intervention days 3, 7, 14, 30, 45 and 60)
- Maximum voluntary inspiratory volume individual time points(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- First 2 months area under the curve of the maximum voluntary inspiratory volume(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, 45, and 60)
- Pain during spirometry(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Awakenings due to pain(Collected on post-intervention days 1, 2, 3, 7, 14, 21, 30, and 45; as well as months 2, 3, 6, 9, and 12)
- Post-Traumatic Stress Disorder checklist (PCL-5)(Day of intervention (prior to intervention))
研究者
Brian M. Ilfeld, MD, MS
Professor of Anesthesiology
University of California, San Diego