Methoxyflurane and Fentanyl in LBNP

NCT04641949 — Phase 4, Completed, 15 participants, Oslo University Hospital

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

Registry	NCT04641949
Status	Completed
Phase	Phase 4
Study type	Interventional; randomized, crossover, masking: triple, basic science
Enrollment	15 (Actual)
Sponsor	Oslo University Hospital (Other)
Conditions	Hypovolemia, Cardiac Output, Low, Analgesia
Interventions	Lower body negative pressure (LBNP) (Procedure)
Dates	start 2020-11-18, primary completion 2022-03-08, completion 2022-03-08, first posted 2020-11-24, last updated 2022-06-30
Locations	1 site in Norway

-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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
Methoxyflurane	Active comparator	Procedure: Lower body negative pressure (LBNP)	Inhalation methoxyflurane 99,9%, 3 ml, single dose. Intravenous NaCl 9 mg/ml, XX ml, single dose.
Fentanyl	Active comparator	Procedure: Lower body negative pressure (LBNP)	Intravenous fentanyl 50 microgr/ml, XX ml, single dose Inhalation NaCl 9 mg/ml, 3 ml, single dose.
Placebo	Placebo comparator	Procedure: Lower body negative pressure (LBNP)	Intravenous NaCl 9 mg/ml, XX ml, single dose. Inhalation NaCl 9 mg/ml, 3 ml, single dose.

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.

+Outcome measures

Primary outcomes

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

Secondary outcomes

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

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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

+Locations (1)

Facility	City	Country	Status
Oslo University Hospital	Oslo	Norway

+Publications

Results publication: 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