Comparison of Lormetazepam and Midazolam Used as Sedatives for Patients That Require Intensive Care
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|ClinicalTrials.gov Identifier: NCT02022592|
Recruitment Status : Completed
First Posted : December 30, 2013
Last Update Posted : May 27, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Sedation in Intensive Care Unit Patients||Drug: Lormetazepam Drug: Midazolam||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||84 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Comparison of Lormetazepam and Midazolam Used as Sedatives for Patients That Require Intensive Care|
|Actual Study Start Date :||July 17, 2014|
|Actual Primary Completion Date :||December 12, 2019|
|Actual Study Completion Date :||March 12, 2020|
The patient is treated on ICU not longer than 2 days. Dosage requirements according to Summary of product characteristics (Sedalam®).
Active Comparator: Midazolam
The patient is treated on ICU not longer than 2 days. Dosage requirements according to Summary of product characteristics (Midazolam-ratiopharm®, Midazolam-hameln®).
- Controllability of sedation [ Time Frame: Up to 8 days ]Controllability of sedation is defined as the percentage share of measures where the actual depth of sedation (measured with the Richmond Agitation and Sedation Scale) (RASS)) matches the target depths of sedation. The individual sedation target is defined by the attending physician. It will be measured until 5 days after termination of study drug.
- SOFA (Sequential Organ Failure Assessment) [ Time Frame: Up to 8 days ]
- Pain-Scores [ Time Frame: Up to 28 days ]
NRS-V (Numeric Rating Scale -V) and FPS-R (Faces Pain Scale-Revised) and BPS (Behavioral Pain Scale) and BPS-NI (Non-Intubated BPS)
according to German consensus guidelines
- Anxiety-Score [ Time Frame: Up to 28 days ]Faces Anxiety Scale score
- Concurrent medication for Analgesia and Sedation [ Time Frame: up to 8 days ]dose/time. It will be measured until 5 days after termination of study drug.
- Delirium-screening-Instruments [ Time Frame: Up to 28 days ]CAM-ICU (Confusion Assessment Method for Intensive Care Unit) ICDSC ( Intensive Care Delirium Screening Checklist) Nu-DESC (Nursing Delirium Screening Scale)
- Mortality [ Time Frame: Up to 90 days ]
- Duration of mechanical ventilation and weaning from mechanical ventilation [ Time Frame: During intensive care unit stay, an average of 14 days ]
- Length of intensive care unit stay [ Time Frame: During intensive care unit stay, an average of 14 days ]
- Length of hospital stay [ Time Frame: During hospital stay, an average of 28 days ]
- Follow-up treatment regarding Patient- Documentation-Management-System [ Time Frame: During hospital stay, an average of 28 days ]Discharge Mode
- Length of sedation [ Time Frame: During intensive care unit stay, an average of 14 days ]
- Number of changes in target Richmond agitation sedation scale (RASS) [ Time Frame: Up to 3 days ]During administration of study drug
- Wake-up-time [ Time Frame: Up to 3 days ]During administration of study drug
- Deviation from target Richmond agitation sedation scale (RASS) [ Time Frame: Up to 3 days ]During administration of study drug
- Quality of Life [ Time Frame: Up to 90 days ]Questionnaire designed to measure health status (EQ-5D)
- Cognition [ Time Frame: Up to 28 days, at hospital discharge ]Minimental State Examination (MMSE) and Cambridge Cognition - computerised cognitive testing (CANTAB®), Mehrfachwahl-Wortschatz-Intelligenztest (MWT) and Fragebogen erlebter Aufmerksamkeitsdefizite (FEDA)
- Posttraumatic stress disorder [ Time Frame: Up to 90 days ]The Post-Traumatic Stress Syndrome 14-Questions Inventory
- Bedside measurement of Acetylcholinesterase activity (U/gHb) [ Time Frame: Up to 8 days ]The Acetylcholinesterase activity will be measured on every study day out of a blood sample (10µl); It will be measured until 5 days after termination of study drug.
- Organ dysfunctions [ Time Frame: Up to 8 days ]It will be measured until 5 days after termination of study drug.
- Depth of sedation [ Time Frame: During the operation ]Depth of sedation is measured by Electroencephalography and Electromyography (only surgical patients in the Centers Charité and Gießen, intensive care unit patients only Center Charité)
- Photomotor reflex [ Time Frame: During intensive care unit stay, an average of 14 days ]Photo motor reflex variations are measured by video pupillometry (only Center Charité)
- Pain threshold measurement [ Time Frame: Up to 3 days ]Automatic measurement of specific pain reflexes
- micro ribonucleic acid (rna) [ Time Frame: Up to 3 days ]micro rna panel is analysed (only Center Charité)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02022592
|Clinic for Anesthesiology, Intensive Care Medicine and Painmanagement, Johann-Wolfgang-Goethe-University|
|Frankfurt, Frankfurt Am Main, Germany, 60590|
|Clinic for Operative Intensive Care Medicine and Intermediate Care, University of RWTH|
|Aachen, Germany, 52056|
|Department of Anesthesiology and Intensive Care Medicine, Charité - University Medicine|
|Berlin, Germany, 13353|
|Study Chair:||Claudia Spies, MD, Univ.- Prof.||Charite University, Berlin, Germany|
|Study Director:||Gernot Marx, MD, Univ.-Prof.||University RWTH Aachen|