Methoxyflurane and Fentanyl in LBNP
Primary Purpose
Hypovolemia, Cardiac Output, Low, Analgesia
Status
Completed
Phase
Phase 4
Locations
Norway
Study Type
Interventional
Intervention
Lower body negative pressure (LBNP)
Sponsored by
About this trial
This is an interventional basic science trial for Hypovolemia focused on measuring Methoxyflurane, Fentanyl
Eligibility Criteria
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
Sites / Locations
- Oslo University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Methoxyflurane
Fentanyl
Placebo
Arm Description
Inhalation methoxyflurane 99,9%, 3 ml, single dose. Intravenous NaCl 9 mg/ml, XX ml, single dose.
Intravenous fentanyl 50 microgr/ml, XX ml, single dose Inhalation NaCl 9 mg/ml, 3 ml, single dose.
Intravenous NaCl 9 mg/ml, XX ml, single dose. Inhalation NaCl 9 mg/ml, 3 ml, single dose.
Outcomes
Primary Outcome Measures
Cardiac output
Cardiac output as measured by suprasternal Doppler and/ or non-invasive (volume clamp) pulse contour analysis.
Secondary Outcome Measures
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
Mean arterial pressure
Change in mean arterial blood pressure with increasing LBNP, as measured by the volume-clamp method.
Stroke volume
Change in cardiac stroke volume with increasing LBNP, as measured by suprasternal Doppler and/ or the volume-clamp method.
Full Information
NCT ID
NCT04641949
First Posted
November 18, 2020
Last Updated
June 28, 2022
Sponsor
Oslo University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04641949
Brief Title
Methoxyflurane and Fentanyl in LBNP
Official Title
Methoxyflurane and Fentanyl in the Lower Body Negative Pressure Model of Hypovolemia in Healthy Volunteers; a Randomized, Placebo-controlled Crossover Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
November 18, 2020 (Actual)
Primary Completion Date
March 8, 2022 (Actual)
Study Completion Date
March 8, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypovolemia, Cardiac Output, Low, Analgesia
Keywords
Methoxyflurane, Fentanyl
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Randomized, placebo controlled, crossover study.
Masking
ParticipantCare ProviderInvestigator
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.
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Methoxyflurane
Arm Type
Active Comparator
Arm Description
Inhalation methoxyflurane 99,9%, 3 ml, single dose. Intravenous NaCl 9 mg/ml, XX ml, single dose.
Arm Title
Fentanyl
Arm Type
Active Comparator
Arm Description
Intravenous fentanyl 50 microgr/ml, XX ml, single dose Inhalation NaCl 9 mg/ml, 3 ml, single dose.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous NaCl 9 mg/ml, XX ml, single dose. Inhalation NaCl 9 mg/ml, 3 ml, single dose.
Intervention Type
Procedure
Intervention Name(s)
Lower body negative pressure (LBNP)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cardiac output
Description
Cardiac output as measured by suprasternal Doppler and/ or non-invasive (volume clamp) pulse contour analysis.
Time Frame
Measured continuously during LBNP-exposure.
Secondary Outcome Measure Information:
Title
Time to hemodynamic decompensation
Description
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
Time Frame
15 minutes
Title
Mean arterial pressure
Description
Change in mean arterial blood pressure with increasing LBNP, as measured by the volume-clamp method.
Time Frame
Measured continuously during LBNP-exposure.
Title
Stroke volume
Description
Change in cardiac stroke volume with increasing LBNP, as measured by suprasternal Doppler and/ or the volume-clamp method.
Time Frame
Measured continuously during LBNP-exposure.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0586
Country
Norway
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Methoxyflurane and Fentanyl in LBNP
We'll reach out to this number within 24 hrs