Efficacy and Safety of Methoxyflurane Vaporized (PENTHROX®) in the Treatment of Acute Trauma Pain in Pre-hospital Setting and in the Emergency Department in Italy: a Multicentre, Randomized, Controlled, Open-label Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 272
- 试验地点
- 16
- 主要终点
- Change in the intensity of pain within 10 minutes.
研究概览
简要总结
The prompt treatment of pain due to minor trauma is often an unmet need in both Emergency Room Department and Ambulance Rescue. Most of the available drugs are intravenously administered and such route of administration may account for delay in the pain relief onset.
Methoxyflurane is an halogenated anesthetic, self-administered by the patient at sub-anesthetic dose through an easy to handle inhaler (Penthrox®). The efficacy and safety of Penthrox® in the treatment of acute traumatic pain will be investigated in an out-of-hospital and in hospital emergency medical care setting.
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
- None
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
- •Written informed consent must be provided by each patient prior to any study-specific activity. In cases where the patient is unable to write autonomously, it must be obtained a verbal consent in presence of a witness that the patient will have to confirm autonomously as soon as (s)he is able
- •Stable, vigilant and collaborative patient i.e. able to understand and communicate with the examiner in order to carry out the study activities
- •Age ≥ 18 years
- •Trauma to the limbs (fracture, dislocation, crushing, bruising) in a single district.
- •N.B. For recruiting, given the particular setting, no instrumental confirmation is required but suspicion of involvement of a single district is sufficient.
- •Moderate to severe pain, detected by the Numerical Rating Scale (NRS score ≥4)
排除标准
- •Personal or family history (parents or siblings) for malignant hyperthermia.
- •History of severe adverse reactions to inhaled anesthetics.
- •History of renal failure
- •History of liver failure.
- •Trauma risky dynamics (ejection from the vehicle, cabin deformation, death of an occupant of the same vehicle, motor vehicle / pedestrian or cyclist impact with a motor vehicle in motion, projection / overturn, fall from a height of> 3 meters, extraction on event place > 20 min).
- •Altered level of vigilance and / or conscience (GCS <15)
- •Symptomatic hypotension or Systolic Pressure <100 mm / Hg
- •Discomfort with Respiratory Rate > 20 and Oxygen Saturation <95%
- •Known pregnancy status.Note: a 1 day delay with respect to the planned menstruation date (28days since the beginning of the previous one) has to be considered a suspected pregnancy.
- •Hypersensitivity to methoxyflurane, to any fluorinated anesthetic or to the E321 butylhydroxytoluene excipient.
- •Current treatment with any analgesic for chronic pain or in the previous 5 hours (8 hours in the case of diclofenac).
- •Known allergy to both paracetamol and non-steroidal anti-inflammatory drugs or known hypersensitivity to morphine
- •All types of acute abdomen and paralytic ileus
- •Hearth failure
- •Recent (within2 months) biliary tract surgery
- •Current bronchial asthma attack
- •Uncontrolled epilepsy
- •Depressive state treated with Monoamine Oxidase Inhibitors (ongoing or interrupted less 3 wks ago)
- •Treatment with naltrexone
- •History of active or recurrent peptic ulcer/hemorrhage (2 or more episodes of documented ulceration or bleeding in the last 6 months)
- •Bleeding diathesis
- •Current Intensive diuretic therapy
- •Chronic dyspepsia, gastritis with significant episodes in the last 2 months
- •Leucopenia and thrombocytopenia, current hemorrhages
- •Current anticoagulant therapy
研究组 & 干预措施
A_test drug_Methoxyflurane (Penthrox®)
Pain from moderate to severe (NRS score 4-10). 3 ml of methoxyflurane vaporized through the Penthrox® inhaler. The drug is self administered under the supervision of investigators/study nurse. The treatment duration is about 25 minutes. The patient is instructed to breath normally and to close the diluter aperture via his/her forefinger to increase the analgesic effect, if needed. In case of pain increase or insufficient pain relief the investigator is allowed to administer a rescue medication as per local routine practice.
干预措施: Methoxyflurane and Penthrox inhaler (Combination Product)
B_comparator_Morphine/Paracetamol/Ketoprofen
The comparator to be administered will vary according to pain intensity and local clinical practice.
In case of severe pain (NRS score ≥ 7), morphine will be administered at a dose of 0.10 mg/kg body weight.
In case of moderate pain (NRS score 4-6) paracetamol or ketoprofen will be administered respectively at a 1 g and 100 mg dose.
All comparator will be administered by intravenous drip in a maximum 10 minutes time of infusion. .
Maximum time of infusion 10 minutes.
干预措施: Morphine (Drug)
B_comparator_Morphine/Paracetamol/Ketoprofen
The comparator to be administered will vary according to pain intensity and local clinical practice.
In case of severe pain (NRS score ≥ 7), morphine will be administered at a dose of 0.10 mg/kg body weight.
In case of moderate pain (NRS score 4-6) paracetamol or ketoprofen will be administered respectively at a 1 g and 100 mg dose.
All comparator will be administered by intravenous drip in a maximum 10 minutes time of infusion. .
Maximum time of infusion 10 minutes.
干预措施: Paracetamol (Drug)
B_comparator_Morphine/Paracetamol/Ketoprofen
The comparator to be administered will vary according to pain intensity and local clinical practice.
In case of severe pain (NRS score ≥ 7), morphine will be administered at a dose of 0.10 mg/kg body weight.
In case of moderate pain (NRS score 4-6) paracetamol or ketoprofen will be administered respectively at a 1 g and 100 mg dose.
All comparator will be administered by intravenous drip in a maximum 10 minutes time of infusion. .
Maximum time of infusion 10 minutes.
干预措施: Ketoprofen (Drug)
结局指标
主要结局
Change in the intensity of pain within 10 minutes.
时间窗: From baseline up to 10 minutes later.
The change in the pain intensity occurring from baseline (patient randomization) up to 10 minutes later. The pain intensity is measured by a 100 mm Visual-Analogic Scale (VAS). The pain intensity is measured at the baseline and after 3, 5, 10 minutes and the difference with the baseline measure is calculated. The changes (differences) from baseline will be compared between the two arms regardless the class of intensity pain (moderate + severe) and for the class of moderate pain.
次要结局
- Need for rescue medication.(From baseline up to 30 minutes later.)
- Change in the intensity of pain within 30 minutes.(From baseline up to 30 minutes later.)
- Incidence of investigational medicinal drug misuse/abuse(From baseline up to 30 minutes later or to the end of the treatment (whichever occurs first).)
- Time to pain relief.(From baseline up to 30 minutes.)
- Global assessment of treatment efficacy perceived by the patient.(From baseline to 30 minutes later or to the end of the treatment (whichever occurs first).)
- Global assessment of treatment practicality in the investigator's opinion.(From baseline to 30 minutes later or to the end of the treatment (whichever occurs first).)
- Need for dilution hole closure (only Experimental Arm).(From baseline up to 30 minutes later.)
- Change in the intensity of pain within 30 minutes by trauma type.(From baseline up to 30 minutes later.)
- Incidence of Treatment-Emergent Adverse Events (AE)(From baseline up to 16 days later.)
- Change in pulse rate(From baseline up to 30 minutes later.)
- Change in blood pressure(From baseline up to 30 minutes later.)
- Change in respiration rate(From baseline up to 30 minutes later.)
- Incidence of treatment-emergent pregnancy(From baseline up to 16 days later. The follow-up until delivery is out from the scope of the trial.)