Methoxyflurane and Fentanyl in LBNP

Sponsor

Oslo University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT04641949

Collaborator

(none)

Enrollment

Location

Arms

15.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypovolemia Cardiac Output, Low Analgesia	Procedure: Lower body negative pressure (LBNP)	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Randomized, placebo controlled, crossover study.Randomized, placebo controlled, crossover study.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

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.

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Nov 18, 2020

Actual Primary Completion Date :

Mar 8, 2022

Actual Study Completion Date :

Mar 8, 2022

Arms and Interventions

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.

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)

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)

Outcome Measures

Primary Outcome Measures

Cardiac output [Measured continuously during LBNP-exposure.]
Cardiac output as measured by suprasternal Doppler and/ or non-invasive (volume clamp) pulse contour analysis.

Secondary Outcome Measures

Time to hemodynamic decompensation [15 minutes]
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
Mean arterial pressure [Measured continuously during LBNP-exposure.]
Change in mean arterial blood pressure with increasing LBNP, as measured by the volume-clamp method.
Stroke volume [Measured continuously during LBNP-exposure.]
Change in cardiac stroke volume with increasing LBNP, as measured by suprasternal Doppler and/ or the volume-clamp method.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oslo University Hospital	Oslo		Norway	0586

Sponsors and Collaborators

Oslo University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Lars Øivind Høiseth, Overlege, PhD, Oslo University Hospital

ClinicalTrials.gov Identifier:

NCT04641949

Other Study ID Numbers:

lbnp_methoxy_fent_2019

First Posted:

Nov 24, 2020

Last Update Posted:

Jun 30, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Lars Øivind Høiseth, Overlege, PhD, Oslo University Hospital

Methoxyflurane

Fentanyl

Additional relevant MeSH terms:

Cardiac Output, Low

Hypovolemia

Study Results

No Results Posted as of Jun 30, 2022