Methoxyflurane and Fentanyl in LBNP

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hypovolemia, Cardiac Output, Low, Analgesia

Intervention / Treatment
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* Procedure: Lower body negative pressure (LBNP)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, placebo controlled, crossover study.
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methoxyflurane, Fentanyl