Determination of Analgesic Equipotent Doses of Inhaled Metoxyflurane vs. Intravenous Fentanyl

NCT03894800 | Completed Phase 4

• 2 other identifiers: 2018-0910-32018-003939-30
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determinate the equipotent doses of inhaled metoxyflurane vs. intravenous fentanyl.

Conditions

Acute Pain; Trauma; Hypovolemia

Keywords

metoxyflurane; pain; fentanyl; cold pressor test

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  90 seconds

Secondary Outcomes (1)

• 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

Study Arms (4)

Methoxyflurane (M)

ACTIVE COMPARATOR

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.

Drug: Methoxyflurane (M); Drug: NaCl (C)

Fentanyl (F1)

ACTIVE COMPARATOR

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.

Drug: Fentanyl (F1); Drug: NaCl (C)

Fentanyl (F2)

ACTIVE COMPARATOR

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.

Drug: Fentanyl (F2); Drug: NaCl (C)

NaCl (C)

PLACEBO COMPARATOR

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.

Drug: NaCl (C)

Interventions

Methoxyflurane (M) DRUG

The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention inhalation of metoxyflurane 3 ml and NaCl i.v. will be administered.(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.

Also known as: NaCl

Methoxyflurane (M)

Fentanyl (F1) DRUG

The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention fentanyl 0.025 mg i.v. and NaCl for inhalation will be administered(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.

Also known as: NaCl (C)

Fentanyl (F1)

Fentanyl (F2) DRUG

The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention fentanyl 0.05 mg i.v. and NaCl for inhalation will be administered.(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.

Also known as: NaCl (C)

Fentanyl (F2)

NaCl (C) DRUG

The subjects will undergo CPT (cold pressor test) to determine the analgesic effect of the drugs, in this intervention NaCl i.v. and NaCl inhal will be used - placebo(13,14) The CPT will be conducted using a temperature-controlled bath with circulating 3°C water (FP 45-HE Refrigerated/Heating Circulator, Julabo Labortechnic, 77960 Seelback, Germany). The subjects submerge their right hand to the wrist with fingers abducted for up to 90 s. The endpoints are NRS scores every 10 s.This test will be performed 3 times for each session.

Fentanyl (F1); Fentanyl (F2); Methoxyflurane (M); NaCl (C)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers
• Age 18 - 64
• Both sex
• 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

You may not qualify if:

• 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
• Pregnancy
• Know allergies or serious side effects to opioids or metoxyflurane
• Use of alcohol last 24 h before each session
• 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
• Elevated intracranial pressure or brain trauma
• Hypovolemia or hypotension
• Myasthenia gravis
• Use metoxyflurane as anesthetic
• Hypersensitivity opposite metoxyflurane or fluorinated anesthetics

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Harald Lenz

Oslo, Norway

Location

Related Publications (8)

• Albrecht E, Taffe P, Yersin B, Schoettker P, Decosterd I, Hugli O. Undertreatment of acute pain (oligoanalgesia) and medical practice variation in prehospital analgesia of adult trauma patients: a 10 yr retrospective study. Br J Anaesth. 2013 Jan;110(1):96-106. doi: 10.1093/bja/aes355. Epub 2012 Oct 11.

  PMID: 23059961 RESULT

• Neighbor ML, Honner S, Kohn MA. Factors affecting emergency department opioid administration to severely injured patients. Acad Emerg Med. 2004 Dec;11(12):1290-6. doi: 10.1197/j.aem.2004.07.014.

  PMID: 15576519 RESULT

• Stephen CR. Clinical applications of methoxyflurane. Acta Anaesthesiol Scand Suppl. 1966;24:215-22. doi: 10.1111/j.1399-6576.1966.tb01127.x. No abstract available.

  PMID: 6003600 RESULT

• Mazze RI. Methoxyflurane revisited: tale of an anesthetic from cradle to grave. Anesthesiology. 2006 Oct;105(4):843-6. doi: 10.1097/00000542-200610000-00031.

  PMID: 17006084 RESULT

• Grindlay J, Babl FE. Review article: Efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting. Emerg Med Australas. 2009 Feb;21(1):4-11. doi: 10.1111/j.1742-6723.2009.01153.x.

  PMID: 19254307 RESULT

• Rosen M, Latto P, Asscher AW. Kidney function after methoxyflurane analgesia during labour. Br Med J. 1972 Jan 8;1(5792):81-3. doi: 10.1136/bmj.1.5792.81.

  PMID: 5007074 RESULT

• Clark RB, Beard AG, Thompson DS. Renal function in newborns and mothers exposed to methoxyflurane analgesia for labor and delivery. Anesthesiology. 1979 Nov;51(5):464-6. doi: 10.1097/00000542-197911000-00020. No abstract available.

  PMID: 496064 RESULT

• Lenz H, Hoiseth LO, Comelon M, Draegni T, Rosseland LA. Determination of equi-analgesic doses of inhaled methoxyflurane versus intravenous fentanyl using the cold pressor test in volunteers: a randomised, double-blinded, placebo-controlled crossover study. Br J Anaesth. 2021 May;126(5):1038-1045. doi: 10.1016/j.bja.2020.12.045. Epub 2021 Mar 4.

  PMID: 33676727 DERIVED

MeSH Terms

Conditions

Acute Pain; Wounds and Injuries; Hypovolemia; Pain

Interventions

Methoxyflurane; Fentanyl

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Ethyl Ethers; Ethers; Organic Chemicals; Methyl Ethers; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Harald Lenz, Phd

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized, double blind, placebo-controlled crossover study.

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 29, 2019
• Study Start: April 23, 2019
• Primary Completion: October 29, 2019
• Study Completion: October 29, 2019
• Last Updated: November 19, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)