Clinical Trials Register

Summary
EudraCT Number:	2012-000188-25
Sponsor's Protocol Code Number:	LoveMi
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2012-000188-25

A.3

Full title of the trial

Lormetazepam versus Midazolam used as sedatives for critically ill
patients.

Lormetazepam versus Midazolam als Basissedativum
für intensivpflichtige Patienten
Multizentrische, randomisierte, kontrollierte, prospektive, doppelblinde, zweiarmige klinische Prüfung nach dem AMG, Phase IV mit Rekalkulation der Fallzahl.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Comparison of Lormetazepam and Midazolam used as sedatives for patients that require intensive care.

Lormetazepam versus Midazolam als Beruhigungsmittel
für intensivpflichtige Patienten

A.3.2

Name or abbreviated title of the trial where available

LoveMi

A.4.1

Sponsor's protocol code number

LoveMi

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02022592

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Charité - Universitätsmedizin Berlin
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Charité - Universitätsmedizin Berlin
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Charité - Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Univ.-Prof. Dr. C. Spies
B.5.3	Address:
B.5.3.1	Street Address	Augustenburger Platz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13353
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4930551 001 / 02
B.5.5	Fax number	+4930551 909
B.5.6	E-mail	claudia.spies@charite.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SEDALAM® 2 mg/10 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Dr. Franz Köhler Chemie GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PR1: Lormetazepam
D.3.9.1	CAS number	848-75-9
D.3.9.3	Other descriptive name	LORMETAZEPAM
D.3.9.4	EV Substance Code	SUB08588MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Midazolam-hameln® 100 mg/50 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	hameln pharmaceuticals GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PR2: MIDAZOLAM
D.3.9.1	CAS number	59467-70-8
D.3.9.4	EV Substance Code	SUB08950MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sedation

E.1.1.1

Medical condition in easily understood language

Tranquilizing

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

“Controllability of sedation”; this 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.

E.2.2

Secondary objectives of the trial

1) Incidence of newly developed complications
2) SOFA Score
3) Pain
4) Anxiety
5) Concurrent medication for Analgesia and Sedation
6) Delirium
7) Mortality
8) Duration of mechanical ventilation and weaning from mechanical ventilation
9) Length of ICU stay
10) Length of hospital stay
11) Discharge mode
12) Length of sedation
13) Number of changes in target sedation depth
14) Wake-up-time
15) Deviation from target sedation depth
16) Quality of Life
17) Cognition
18) Posttraumatic stress disorder
19) Pain threshhold measurement (only Center Charité and Gießen)
20) Depth of sedation (EMG/EEG) (surgery patients: Center Charité and Gießen, intensive care unit patients: Center Charité)
21) Photomotor reflex (only Center Charité)
22) Plasma activity of acetylcholine esterase
23) MicroRNA (only Center Charité)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Mechanically ventilated ICU patients with the need for sedatives
to achieve or maintain the intended target-RASS (surgical/ non-surgical).
-Age ≥ 18 years
-Patients who are incapable of giving consent at study inclusion: Written informed consent by patient’s legal representative or an independent medical consultant, patients give informed consent subsequent if they are capable.
- Patients who are able to give informed consent at study inclusion: Written informed consent by patients for planned postoperative prolonged ventilatory support who undergo general surgery
- Patients who are able to give informed consent at study inclusion and have the need for intubation with analgosedation

E.4

Principal exclusion criteria

-Any bolus administration of benzodiazepines until 72hrs before
inclusion (except from premedication due to anaesthesia).
- Continuous administration of benzodiazepines within the last 7 days before start of study drug application
- Titration phase: No possibility that the target RASS (-3 - 0) can be set by the treating physician
-Known drug intolerance or allergy against lormetazepam,
midazolam or one of the additional components.
-Addictive disorder
-Increased intracranial pressure
-Acute intoxication with alcohol, analgesics, sedatives,
antipsychotics (neuroleptics, anti-depressives, lithium).
-Patients with cerebrale Pathology, which changes the controllability of sedation or die consciousness (e.g. patients known mental retardation due to syndromatic disorders or an
infantile brain damage)
-Patients with a suspected or secured hypoxic brain damage
- Patients with intracranial surgery during actual hospital care
- Tetraplegic patients
-Myasthenia Gravis
-Cerebellar or spinal Ataxia
-Moribund patients with an expected lifespan of less than 24
hours.
-Sickle cell anaemia
-Thallassemia
-Enzyme related disorders that are associated with a severe
decreased activity of UDP-glucoronyltransferase (e.g. M. Crigler-
Najjar)
- Chronic liver insuffiviency CHILD C with MELD Score >
17 before access to intensive care unit
- Diagnosed propofol intolerance/anamnestic propofol infusion syndrome
- known depression/suicidality
-Pregnancy (positive beta-HCG test from urine or positive beta-HCG laboratory test from serum (in anuric patients the serum beta-HCG test is obliged) or lactation
-Woman of child-bearing potential who are not using a highly
effective contraception (Pearl – Index <1) until 3 monthes after study inclusion and during this trial
-Referral following an order of official authorities (court order or
administrative decision) according to German Drug Law (AMG)
§40 (1) 4
-Participation in clinical trials according to the German Drug Law
(AMG) 30 days to and during the study
-Local staff

E.5 End points

E.5.1

Primary end point(s)

“Controllability of sedation”; this is defined as the percentage share of measures where the actual depth of sedation (measured with the Richmond Sedation and Agitation Scale
(RASS)) matches the target depths of sedation. The individual sedation target is defined by the attending physician.

E.5.1.1

Timepoint(s) of evaluation of this end point

This endpoint will be measured for 3 days on ICU.

E.5.2

Secondary end point(s)

1) Incidence of newly developed complications (cardiovascular, pulmonal, gastrointestinal, renal, cerebral und infectious)
2) SOFA
3) Pain-Scores (NRS-V; FPS-R; BPS; BPS-NI according to German consensus guidelines)
4) Anxiety-Score (FAS)
5) Concurrent medication for Analgesia and Sedation (dose/time)
6) Delirium-Screening-Instruments (CAM-ICU/ICDSC/Nu-DESC)
7) Mortality (days)
8) Duration of mechanical ventilation and weaning from mechanical ventilation (days)
9) Length of ICU stay (days)
10) Length of hospital stay (days)
11) Discharge mode (days)
12) Length of sedation (days)
13) Number of changes in target RASS
14) Wake-up-time (hours)
15) Deviation from target RASS
16) Quality of Life (EQ-5D)
17) Cognition (MMSE, FEDA, MWT)
18) Posttraumatic stress disorder (PTSS-14)
19) Pain threshold measurement (only Center Charité and Gießen)
20) Depth of sedation (EMG/EEG) (surgery patients at Center Charité and Gießen, intensive care unit patients at Center Charité)
21) Photomotor reflex (only Center Charité)
22) Plasma activity of acetylcholine esterase
23) MicroRNA (Center Charité)

E.5.2.1

Timepoint(s) of evaluation of this end point

1) will be measured until 5 days after termination of study drug .
13) and 14) and 15 ) will be measured until termination of study drug.
2) and 5) and 20) and 21) and 22) will be measured as long as patient is treated on ICU but not longer than 5 days after study drug termination.
3) and 4) and 6) will be measured until study day 28 or discharge.
18) MMSE and MWT and FEDA will be measured at 28 days (or discharge) and FEDA at 90 days.
8) and 9) and 10) and 11) and and 12) and 16) and 17) and 18) will be measured at follow up (day 90).
19) will be measured during the intervention of 2 days
For 7) there will be a daily assessment and an assessment at follow up.
23) will be measured at inclusion and 24 hours later

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Midazolam

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last patient last visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients from Intensive Care Units and patients who undergo general surgery

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After hospital stay one Follow-up telephone interview will be carried out at 3 months after first application of the study drug.
A patient questionnaire on cognition, quality of life, posttraumatic anxiety will be carried out.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-10-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-03-12

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials