Methoxyflurane and Fentanyl in LBNP

NCT04641949 | Completed Phase 4 DMC

• 1 other identifier: lbnp_methoxy_fent_2019
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a single-centre, placebo-controlled, crossover study on healthy volunteers aiming to explore non-inferiority of methoxyflurane and fentanyl compared to placebo on the tolerance to hypovolemia.

Conditions

Hypovolemia; Cardiac Output, Low; Analgesia

Keywords

Methoxyflurane; Fentanyl

Outcome Measures

Primary Outcomes (1)

• Cardiac output

  Cardiac output as measured by suprasternal Doppler and/ or non-invasive (volume clamp) pulse contour analysis.

  Measured continuously during LBNP-exposure.

Secondary Outcomes (3)

• Time to hemodynamic decompensation

  15 minutes

• Mean arterial pressure

  Measured continuously during LBNP-exposure.

• Stroke volume

  Measured continuously during LBNP-exposure.

Study Arms (3)

Methoxyflurane

ACTIVE COMPARATOR

Inhalation methoxyflurane 99,9%, 3 ml, single dose. Intravenous NaCl 9 mg/ml, XX ml, single dose.

Procedure: Lower body negative pressure (LBNP)

Fentanyl

ACTIVE COMPARATOR

Intravenous fentanyl 50 microgr/ml, XX ml, single dose Inhalation NaCl 9 mg/ml, 3 ml, single dose.

Procedure: Lower body negative pressure (LBNP)

Placebo

PLACEBO COMPARATOR

Intravenous NaCl 9 mg/ml, XX ml, single dose. Inhalation NaCl 9 mg/ml, 3 ml, single dose.

Procedure: Lower body negative pressure (LBNP)

Interventions

Lower body negative pressure (LBNP) PROCEDURE

LBNP is a model of experimental hypovolemia, whereby the lower body is exposed to negative pressure leading to sequestering of blood in the lower body and central hypovolemia. LBNP will be induced stepwise with increments of 10 mmHg, each level lasting 1 min. LBNP will be terminated at symptoms or signs of impending hemodynamic collapse.

Fentanyl; Methoxyflurane; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be at least 18 years of age.
• Must be below 65 years of age.
• Signed informed consent and expected cooperation for the study and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

You may not qualify if:

• Any medical condition limiting physical excertional capacity or requiring regular medication (allergy and oral contraceptives excepted)
• Pregnancy
• History of syncope (syncope of presumed vasovagal nature with known precipitating factor excepted)
• Any known cardiac arrhythmia
• History of renal disease
• History of liver disease
• Previous substance abuse
• Allery or known serious side-effects to opioids or methoxyflurane

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0586, Norway

Location

Related Publications (1)

• Hoiseth LO, Fjose LO, Hisdal J, Comelon M, Rosseland LA, Lenz H. Haemodynamic effects of methoxyflurane versus fentanyl and placebo in hypovolaemia: a randomised, double-blind crossover study in healthy volunteers. BJA Open. 2023 Jun 28;7:100204. doi: 10.1016/j.bjao.2023.100204. eCollection 2023 Sep.

  PMID: 37638077 DERIVED

MeSH Terms

Conditions

Hypovolemia; Cardiac Output, Low; Agnosia

Interventions

Lower Body Negative Pressure

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Decompression; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Both drug interventions (intravenous fentanyl and inhaled methoxyflurane) will have NaCl placebo comparators. As the methoxyflurane has a characteristic smell, some drops of methoxyflurane will be placed on the exterior of the placebo methoxyflurane inhalation devices. Further, the subjects will rinse the mouth with a mouthwash shortly before inhalation to cover the taste of methoxyflurane.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Overlege, PhD

Model Details: Randomized, placebo controlled, crossover study.

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 24, 2020
• Study Start: November 18, 2020
• Primary Completion: March 8, 2022
• Study Completion: March 8, 2022
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)