Ignite Creation Date:
2025-12-24 @ 3:15 PM
Ignite Modification Date:
2026-02-23 @ 6:27 AM
Study NCT ID:
NCT02022592
Status:
COMPLETED
Last Update Posted:
2022-04-13
First Post:
2013-12-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Comparison of Lormetazepam and Midazolam Used as Sedatives for Patients That Require Intensive Care
Sponsor:
Claudia Spies
Organization:
Study Overview
Official Title:
Comparison of Lormetazepam and Midazolam Used as Sedatives for Patients That Require Intensive Care
Status:
COMPLETED
Status Verified Date:
2022-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A goal directed , demand-driven administration of sedative drugs is an integral part of every intensive care treatment. During long-term application of sedatives, Midazolam is the most commonly used sedative in Europe.
One major objective is the problem of oversedation and agitation during an intensive care treatment due to the lack of controllability of available substances.
The Love-Mi RCT investigates the clinical controllability of Midazolam versus the newly available intravenous drug Lormetazepam.
One major objective is the problem of oversedation and agitation during an intensive care treatment due to the lack of controllability of available substances.
The Love-Mi RCT investigates the clinical controllability of Midazolam versus the newly available intravenous drug Lormetazepam.
Detailed Description:
Midazolam is almost exclusively metabolized intrahepatically. The methyl-group at position 1 of the imidazole ring is oxidized by liver enzymes. The product is a-OH-midazolam. This reaction is catalyzed by a p450-dependent oxidase in the liver.
Active a-OH-midazolam is inactivated by a biotransformation type II reaction after conjugation. The water soluble, conjugated midazolam can be excreted by the kidney.
During an intensive care treatment, the p450 dependent metabolization is known to be a "bottleneck of elimination" as many drugs are inactivated by this pathway.
As the phase II (glucuronidation) is non-saturable in practice - the phase I reaction limits the metabolic capacity. This leads to unpredictable prolongation of midazolam effects.
In contrast, Lormetazepam is glucuronized directly at its OH-group during a phase II reaction. Since the glucuronidation is non-saturable, Lormetazepam is metabolized with nearly constant kinetics even if repeatedly administered.
Due to the pharmacokinetics we hypothesize that Lormetazepam has an improved controllability compared to midazolam. As this leads to less frequent agitation and over-sedation, we hypothesize that there are multiple beneficial clinical outcomes for patients treated with lormetazepam instead of midazolam.
Active a-OH-midazolam is inactivated by a biotransformation type II reaction after conjugation. The water soluble, conjugated midazolam can be excreted by the kidney.
During an intensive care treatment, the p450 dependent metabolization is known to be a "bottleneck of elimination" as many drugs are inactivated by this pathway.
As the phase II (glucuronidation) is non-saturable in practice - the phase I reaction limits the metabolic capacity. This leads to unpredictable prolongation of midazolam effects.
In contrast, Lormetazepam is glucuronized directly at its OH-group during a phase II reaction. Since the glucuronidation is non-saturable, Lormetazepam is metabolized with nearly constant kinetics even if repeatedly administered.
Due to the pharmacokinetics we hypothesize that Lormetazepam has an improved controllability compared to midazolam. As this leads to less frequent agitation and over-sedation, we hypothesize that there are multiple beneficial clinical outcomes for patients treated with lormetazepam instead of midazolam.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: