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临床试验/NCT03671746
NCT03671746已完成1 期

Inflammatory Response to Trauma - Does Early Cytokine Modulation Improve Patient Outcome

Arun Aneja1 个研究点 分布在 1 个国家目标入组 70 人开始时间: 2019年2月28日最近更新:
适应症
干预措施

试验速览

阶段
1 期
状态
已完成
发起方
入组人数
70
试验地点
1
主要终点
Length of Hospital Stay

研究概览

简要总结

It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements in orthopaedic patient population, and improved patient subjective pain after hospital discharge. Preliminary animal and clinical studies have shown correlation between elevated blood cytokine concentrations during the acute phase of trauma and the development of post-traumatic complications. Early administration of nonsteroidal anti-inflammatory drug (NSAID) in animals significantly reduced inflammatory profiles, improved pulmonary edema, and enhanced arteriole vasoconstriction in response to hemorrhage. The ability to modify post-traumatic physiologic response via short-term administration of a non-steroidal anti-inflammatory drug (NSAID) may lead to improved patient outcome. In addition, given the current landscape for opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.

By doing this study, the investigators hope to learn how to provide the best care for all patients in the state of Kentucky. Patient participation in this research will last about 1 year.

详细描述

Accidental trauma is the 4th leading cause of death in the United States, and it is associated with a complex inflammatory response. This response is associated with post-traumatic complications such as; multi-organ dysfunction syndrome (MODS), bacterial pneumonia, acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), and post-traumatic pain (PTP). It is unknown whether early modulation of inflammatory cytokines is associated with improved patient outcomes, reduced narcotic requirements, and improved patient subjective pain after hospital discharge.

Preliminary data has shown: (1) elevated blood cytokine concentrations during the acute phase of trauma are correlated with the development of fatal post-traumatic complications, (2) that early administration of a non-steroidal anti-inflammatory drug (NSAID) resulted in decreased blood serum levels of interleukin (IL-6), Prostaglandin E2 (PGE2), improved pulmonary edema, and enhanced arterioles ability to vasoconstrict in response to hemorrhage in animal models, and (3) that the addition of the internal physiologic parameters (inflammatory cytokines) to New Injury Severity Score (NISS - a marker of the external anatomical insult) significantly improves the ability to predict hospital length of stay of trauma patients when compared to NISS alone. The investigator's group is the first to use an integrative approach that combines the external anatomic injury data with the internal physiologic response for accurate prediction of a patient's clinical outcome. Therefore, if the investigators apply this same mindset to treatment, the investigators can improve the trauma patients' care by addressing both parameters as opposed to solely focusing on the external injury as done in the past. The ability to modify post-traumatic physiologic response via short-term administration of an NSAID may lead to improved patient outcomes.

Over the last decade, clinicians have remained puzzled over the safety of NSAID administration after fracture in terms of bone union. In addition, given the current landscape for the opioid epidemic in the United States, alternative non-opioid pain management during acute trauma has the potential to reduce opioid consumption and represents a pivotal component of multimodal analgesia strategy.

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

Participant medical team will be blinded to the treatment or placebo intervention

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

入选标准

  • Patients age 18 to 75
  • New Injury Severity Score (NISS) > 9, with musculoskeletal injury requiring surgical treatment

排除标准

  • Patient age < 18 or > 75
  • Patients who presented more than 24 hours after time of injury
  • Patients with contraindications to NSAID therapy (i.e., patients with active hemorrhage, received blood products, traumatic brain injury (TBI), active gastrointestinal bleeding or ulceration, NSAID allergy, thromboembolism, or coagulopathy)
  • Patients with pre-existing inflammatory condition (e.g., inflammatory arthropathy or bowel disease)
  • Patients with preexisting immunocompromised/immunosuppressed condition or acquired immunodeficiency syndrome (AIDS)
  • Patients with pre-existing comorbidities (e.g., coronary artery disease, myocardial infarction, chronic organ failure, chronic obstructive pulmonary disease, emphysema, asthma, etc.)
  • Patients with chronic use of steroids, immuno-modulating drugs, or history of organ transplantation
  • Patients receiving chronic opioid therapy or treatment for opioid use disorder
  • Patients who are pregnant
  • Patients with thermal injury

研究组 & 干预措施

Standard of Care without NSAID

Placebo Comparator

Polytrauma participants will receive standard of care in addition to saline solution according to standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.

干预措施: Saline Solution (Drug)

Standard of Care with NSAID

Experimental

Participants in the group will receive Ketorolac in addition to standard of care for the standard Advanced Trauma Life Support (ATLS) and standard ICU routine medical care.

干预措施: Ketorolac (Drug)

结局指标

主要结局

Length of Hospital Stay

时间窗: Up to 30 days

Duration of the hospital stay will be calculated from electronic health record

次要结局

  • Morphine Milligram Equivalents in House(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Patient Pain Scores(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Interleukin 1a(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Interleukin 1b(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Interleukin 6(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Interleukin 10(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Prostaglandin E-2(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Post Traumatic Complications(Up to 30 days)
  • Mortality(Up to 30 days)
  • Change in Inpatient Subjective Pain Reports(Hospital Day 0 (Enrollment), Day 1, Day 2, Day 3, Day 4, Day 5)
  • Change in Outpatient Subjective Pain Reports(up to 365 days)

研究者

发起方
Arun Aneja
申办方类型
Other
责任方
Sponsor Investigator
主要研究者

Arun Aneja

Assistant Professor of Orthopaedic Surgery Traumatology Division

University of Kentucky

研究点 (1)

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