Methoxyflurane and Fentanyl in LBNP

Methoxyflurane and Fentanyl in the Lower Body Negative Pressure Model of Hypovolemia in Healthy Volunteers; a Randomized, Placebo-controlled Crossover Study

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.

Study Overview

• Status: Completed
• Conditions: Analgesia; Hypovolemia; Cardiac Output, Low
• Intervention / Treatment: Procedure: Lower body negative pressure (LBNP)

Detailed Description

The study will explore the effects of fentanyl and methoxyflurane versus placebo (NaCl; saline) on the hemodynamic response to hypovolemia in healty volunteers. Hypovolemia will be induced in the "lower body negative pressure" model. XX healthy volunteers will be exposed to inhaled methoxyflurane, 3 ml or intravenous fentanyl, XX mg or placebo in a randomized order (cross-over) at least 3 days apart.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0586
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methoxyflurane; Inhalation methoxyflurane 99,9%, 3 ml, single dose. Intravenous NaCl 9 mg/ml, XX ml, single dose.	Procedure: Lower body negative pressure (LBNP); 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.
Active Comparator: Fentanyl; Intravenous fentanyl 50 microgr/ml, XX ml, single dose Inhalation NaCl 9 mg/ml, 3 ml, single dose.	Procedure: Lower body negative pressure (LBNP); 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.
Placebo Comparator: Placebo; Intravenous NaCl 9 mg/ml, XX ml, single dose. Inhalation NaCl 9 mg/ml, 3 ml, single dose.	Procedure: Lower body negative pressure (LBNP); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output	Cardiac output as measured by suprasternal Doppler and/ or non-invasive (volume clamp) pulse contour analysis.	Measured continuously during LBNP-exposure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to hemodynamic decompensation	Time from start LBNP to symtomps or signs of hemodynamic decompensation (and termination of LBNP); defined by: Symptoms of pre-syncope (light-headedness, nausea or sweating); Mean arterial pressure-reduction to less than 75% of baseline for >3 s; Heart rate-reduction to less than 75% baseline for >3 s	15 minutes
Mean arterial pressure	Change in mean arterial blood pressure with increasing LBNP, as measured by the volume-clamp method.	Measured continuously during LBNP-exposure.
Stroke volume	Change in cardiac stroke volume with increasing LBNP, as measured by suprasternal Doppler and/ or the volume-clamp method.	Measured continuously during LBNP-exposure.

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Actual): March 8, 2022
• Study Completion (Actual): March 8, 2022

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Fentanyl; Methoxyflurane
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Hypovolemia; Cardiac Output, Low
• Other Study ID Numbers: lbnp_methoxy_fent_2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No