Determination of Analgesic Equipotent Doses of Inhaled Metoxyflurane vs. Intravenous Fentanyl Using Cold Pressor Test (CPT) in Volunteers: A Randomized, Double Blind, Placebo-controlled Crossover Study.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- NRS (numeric rating scale) scores during the second CPT, which starts 5 minutes after drug administration and lasts for 90 seconds. NRS is a scale from 0 to 10 (0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10). 0 = no pain and 10 = worst pain imaginable.
研究概览
简要总结
The aim of this study is to determinate the equipotent doses of inhaled metoxyflurane vs. intravenous fentanyl.
详细描述
Traumatized patients frequently experience pain prehospital due to the fear of adverse cardiovascular effects (e.g. hypotension) and respiration depression of opioid treatment, leading to insufficient analgesia. Therefore, there is of interest to investigate other analgesics that do not have these adverse effects.
In Norway, methoxyflurane has been approved for the emergency relief of moderate to severe trauma pain in conscious adult patients. Metoxyflurane (Penthrox®) do not have these adverse effects (hypotension and respiration depression). It is easy to administrate via an inhalator, and is therefore suitable for use prehospital. This would possible help to treat pain better prehospital.
There exists no data of how effective metoxyflurane is as an analgesic compared to an opioid. The aim of this study is to determinate the equipotent doses of inhaled metoxyflurane vs. intravenous fentanyl.
Ten healthy volunteers (18 - 64 years) will be enrolled in a randomized, double blind, placebo-controlled, crossover study using a standard experimental pain model: CPT- Cold pressor test (ice water). Our group has used this experimental pain model in earlier studies and a crossover study is suitable to compare different drugs.
Possible side effects will be recorded for both metoxyflurane and fentanyl: sedation, dizziness, itching, nausea and vomiting. Respiration frequency and non-invasive blood pressure will be recorded every as possible low blood pressure or respiration depression can occur.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Labeling of the IMPs will be done by one a nurse anesthetist not participating in the study. The study drugs, will be distributed in a pre-packed in identical, opaque envelopes (the same day as the drugs will be used). The envelopes are not to be broken until randomization of the patient is done
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers
- •Age 18 - 64
- •No chronic disease
- •No regular medication
- •Recruited from the general population
- •Signed informed consent and expected cooperation of the subjects for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations
排除标准
- •Use of pain medication the last 2 days before a session
- •Use of complementary medicine the last 2 days before a session
- •Use of regular medication
- •Previous substance abuse
- •Know allergies or serious side effects to opioids or metoxyflurane
- •Use of alcohol last 24 h before each session
- •Exclusion criteria with respect to fentanyl:
- •Hypersensitivity opposite the active substance (fentanyl) or other opioids
- •Hypersensitivity opposite the excipients (to fentanyl): sodiumclorid, water for injection, hydrochloric acid or sodium hydroxide
- •Respiratory depression without artificial ventilation
- •Use of MAO-inhibitor or use of MAO-inhibitor by two weeks before inclusion
- •Elevated intracranial pressure or brain trauma
- •Hypovolemia or hypotension
- •Myasthenia gravis
- •Exclusion criteria with respect to metoxyflurane:
- •Use metoxyflurane as anesthetic
- •Hypersensitivity opposite metoxyflurane or fluorinated anesthetics
- •Hypersensitivity opposite the excipient (to metoxyflurane):
- •Butylhydroksytoulen
- •Malignant hyperthermia or persons with suspect genetic predisposition for malignant hyperthermia
- •History (to the volunteer or family) of serious adverse effects after administration of inhalation anesthetics
- •Volunteers showing sign of liver damage after use of metoxyflurane or halogenated anesthetics
- •History of liver disease
- •Clinical significant reduced kidney function or history of kidney disease
- •Changed of level of consciousness of any cause, including brain trauma, drugs or alcohol
- •Clinical detected cardiovascular unstability
- •Clinical detected respiratory depression
研究组 & 干预措施
Methoxyflurane (M)
A session starts with a CPT - cold pressor test (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of NaCl intravenous (time -5 minutes). At the same time the subject begin to inhale metoxyflurane through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs. Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: Methoxyflurane (M) (Drug)
Methoxyflurane (M)
A session starts with a CPT - cold pressor test (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of NaCl intravenous (time -5 minutes). At the same time the subject begin to inhale metoxyflurane through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs. Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: NaCl (C) (Drug)
Fentanyl (F1)
A session starts with a CPT (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of fentanyl 0.025 mg intravenous (time -5 minutes). At the same time the subject begin to inhale NaCl through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs.Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: Fentanyl (F1) (Drug)
Fentanyl (F1)
A session starts with a CPT (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of fentanyl 0.025 mg intravenous (time -5 minutes). At the same time the subject begin to inhale NaCl through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs.Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: NaCl (C) (Drug)
Fentanyl (F2)
A session starts with a CPT (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of fentanyl 0.05 mg intravenous (time -5 minutes). At the same time the subject begin to inhale NaCl through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs. Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: Fentanyl (F2) (Drug)
Fentanyl (F2)
A session starts with a CPT (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of fentanyl 0.05 mg intravenous (time -5 minutes). At the same time the subject begin to inhale NaCl through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs. Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: NaCl (C) (Drug)
NaCl (C)
A session starts with a CPT (time -15 minutes). Then a 10 minutes rest before the subject receives a syringe of NaCl intravenous (time -5 minutes). At the same time the subject begin to inhale NaCl through the inhalator. The subject should first take 10 breath through the inhalator. This will take approximately 1-1.5 minutes. The subject then take a break, and then inhale the rest of the dosage before time zero.
At time zero a new CPT will be performed. At time 15 minutes the last CPT will be performed.
The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs. Each test lasts up to 90 seconds and endpoints are NRS scores every 10 second.
干预措施: NaCl (C) (Drug)
结局指标
主要结局
NRS (numeric rating scale) scores during the second CPT, which starts 5 minutes after drug administration and lasts for 90 seconds. NRS is a scale from 0 to 10 (0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10). 0 = no pain and 10 = worst pain imaginable.
时间窗: 90 seconds
NRS (numeric rating scale) scores during CPT (Cold pressor test) 5 minutes after drug administration. The CPT lasts for 90 seconds. The endpoints are NRS scores every 10. second during the CPT.
次要结局
- NRS (numeric rating scale) scores during the second CPT, which starts 20 minutes after drug administration and lasts for 90 seconds. This is a scale from 0 to 10 (0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10). 0 = no pain and 10 = worst pain imaginable.(90 seconds)
研究者
Harald Lenz
Principal Investigator
Oslo University Hospital