Continuous Sedation in Initially Sedated Adults in ICUPhase 3MIDEXNCT00481312
Dexmedetomidine Versus Midazolam for Continuous Sedation in the Intensive Care Unit (ICU)
A Phase 3 study testing Dexmedetomidine and Midazolam in people with Continuous Sedation in Initially Sedated Adults in ICU, run by Orion Corporation, Orion Pharma at 43 sites in 9 countries.
Trial summary
Patients in ICU who need help with their breathing are put onto a machine called a ventilator and are also given a medicine, called a sedative, which helps them to sleep and makes them more comfortable. Midazolam is a sedative that is routinely used for these purposes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Continuous Sedation in Initially Sedated Adults in ICU
- What is being tested?
- Dexmedetomidine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 501 participants
- Where
- 43 sitesin 9 countries
- Study dates
- Jun 2007to Oct 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years and over
- Clinical need for sedation of an initially intubated (or tracheotomised) and ventilated (with inspiratory assistance) patient
- Prescribed light to moderate sedation (target RASS = 0 to -3) using midazolam infusion
- Patients should be randomised within 72 hours from ICU admission and within 48 hours of commencing continuous sedation in the ICU
- Patients should have an expected requirement for sedation of at least 24 hours from time of randomisation
- Written informed consent must be obtained according to local regulations before starting any study procedures other than pre-screening.
Who cannot join
- Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury
- Uncompensated acute circulatory failure at time of randomisation (severe hypotension with MAP < 55 mmHg despite volume and pressors)
- Severe bradycardia (HR < 50 beats/min)
- AV-conduction block II-III (unless pacemaker installed)
- Severe hepatic impairment (bilirubin > 101 µmol/L)
- Need for muscle relaxation at the time of randomisation (may only be used for intubation and initial stabilization)
Show all 20Show fewer
- Loss of hearing or vision, or any other condition which would significantly interfere with the collection of study data
- Burn injuries requiring regular anaesthesia or surgery
- Use of centrally acting α2 agonists or antagonists at the time of randomisation, notably clonidine (see section 5.7 for prior and concomitant treatments)
- Known allergy to any of the study drugs or any excipients of the study drugs
- Patients who have or are expected to have treatment withdrawn or withheld due to poor prognosis
- Patients receiving sedation for therapeutic indications rather than to tolerate the ventilator (e.g. epilepsy)
- Patients unlikely to require continuous sedation during mechanical ventilation (e.g. Guillain-Barré syndrome)
- Patients who are unlikely to be weaned from mechanical ventilation; e.g. diseases/injuries primarily affecting the neuromuscular function of the respiratory apparatus such as clearly irreversible disease requiring prolonged ventilatory support (e.g. high spinal cord injury or advanced amyotrophic lateral sclerosis)
- Distal paraplegia
- Positive pregnancy test or currently lactating
- Received any investigational drug within the preceding 30 days
- Concurrent participation in any other interventional study (any study in which patients are allocated to different treatment groups and/or non-routine diagnostic or monitoring procedures are performed)
- Previous participation in this study
- Any other condition which, in the investigator's opinion, would make it detrimental for the subject to participate in the study
Trial locations and contacts
43 sites in 9 countries.
43 sites in 9 countries
France12 sites
Centre Hospitalier Universitaire d'Angers, Reanimation medicale est de Mededicne Hyperbare, 4 Rue Larrey
Angers, 49933
Centre Hospitalier Victor Dupouy Hopital Dupuytren, Service Reanimation Polyvalente, 69, Rue du Lt Colonel Prud'hon
Argenteuil, 95107
Centre Hospitalier Universitaire de Grenoble, Service de Reanimation Medicale, Boulevard de la Chantourne, BP 217
Grenoble, 38043
Centre Hospitalier La Roche sur Yon CHD les Oudaireis, Service Reanimation CHD la Roche sur Yon, Les Oudairies
La Roche-sur-Yon, 85925
Hopital Albert Calmette, Boulevard Du Pr. Jules Leclercq
Lille, 59037
Centre Hospitalier Universitaire Limoges Hopital Dupuytren, Service de Reanimation Polyvalente, 2, Avenue Martin Luther King
Limoges, 87042
Centre Hospitalier Universitaire d'Orleans, Reanimation Medicale, 1, rue Prote Madeleine, BP 2439
Orléans, 45032
Hopital Bichat-Claude, Dept. D'Anasehesie et Reanimation Chirurgicale, 46, rue Henri-Huchard
Paris, 75018
Groupe Hospitalier Cochin Saint Vincent de Paul, Service de Reanimation Medicale, 27 Rue du Faubourg Saint Jacques
Paris, 75679
Hopital Foch, Service Renimation, 40 Rue Worth, Suresnes Hauts de Seine
Paris, 92150
Centre Hospitalier Universitaire de Poitiers, Reanimation Medicale, 2, Rue de la Miletrie
Poitiers, 86021
Centre Hospitalier Regional et Universitaire - Hopital Bretonneau Service Reanimation Medicale Polyvalente, 2, Boulevard Tonnelle, Tours cedex 9
Tours, 37044
Netherlands8 sites
VU Medisch Centrum, De Boelelaan 1117
Amsterdam, 1081 HV
Gelre Hospitals - Locatie Lucas, A.Schweitzerlaan 32
Apeldoorn, 7334 DZ
Amphia Ziekenhuis, Dept. Intensieve Zorgen, Molengracht 21
Breda, 4818
Albert Schweitzer Hospital, Locatie Dordwikj, Albert Schweitzerplaats 25
Dordrecht, 3318 AT
Kennemer Hospital, Boeerhaavelaan 29
Haarlem, 2035 RC
Saint Elisabeth Ziekenhuis, Dept. Intensieve Zorgen, Hilvarenbeekseweg 60
Tilburg, 5022 GC
Viecuri MC voor Noord-Limburg, Locatie Venlo, Dept. Intensieve Zorgen, Tegelseweg 210
Venlo, 5912 BL
Isala Klinieken, Locatie Weezenlanden, Groot Wezenland 20
Zwolle, 8011 JW
Belgium4 sites
ULB Erasme, Route de Lennik
Brussels, 1070
UZ Brussel, Intensive Care Dept. Laarbeeklaan 101
Brussels, 1090
Universitaer Ziekenhuis Gent, Intensieve Zorgen, De Pintelaan 185
Ghent, 9000
CHU de Liege (Sart Tilman), Domaine de Sart-Tilman
Liège, 3000
Estonia4 sites
East Tallinn Central Hospital, Ravi Stret 18
Tallinn, 10138
North Estonian Regional Hospital, Centre of Intensive Care, J. Sutiste Tee 18
Tallinn, 13419
North Estonian Regional Hospital, Dept. of Postoperative Intensive Care, J. Sutiste Tee 18
Tallinn, 13419
Tartu University Hospistal, Clinic of Anesthesiology and Intensive Care, L. Puusepa 8
Tartu, 51014
Norway4 sites
Haukeland University Hospital, Intensive Care Unit, Jonas Liesvei 65
Bergen, 5021
Rikshospitalet, Universitetsklinikk, Sognsvannsveien 20
Oslo, 0027
Ulleval University Hospital, Medical and Surgical ICU, Kirkeveien 166
Oslo, 0450
Aker Universtetssykehus HF, Anestesiavdelingen, Trondheimsveien 235
Oslo, 0514
Germany3 sites
Universitatsklinikum Bonn, Klinik u. Poliklinik f. Anasthesiologie u. Operative Intensivmedizin, Sigmund-Freud-Strasse 25
Bonn, 53105
Universitatsklinikum Greifswald, Klinik u. Poliklinik f. Anasthesiologie u. Intensivmedizin, Friedrich-Loeffler-Str. 23b
Greifswald, 17475
Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin, Hoppe-Seyler-Strasse 3
Tübingen, 72076
Switzerland3 sites
Inselspital, Freiburgstrasse 4
Bern, CH-3010
Kantonsspital Winterthur, Brauerstrasse 15,
Winterthur, 8401
Universitatsspital Zurich, Klinik fur Innere Medizin, Intensivstation, Ramistrasse 100
Zurich, 8091
United Kingdom3 sites
University Hospital Birmingham, Department of Anaesthesia, Queen Elizabeth Hospital,
Birmingham, B15 2TH
Birmingham Heartlands Hospital, Bordesely Green East
Birmingham, B9 5SS
Derriford Hospital, Dept. of Intensive Care Level 4, Derriford Road
Plymouth, PL6 8DH
Finland2 sites
Oulu University Hospital, Kajaanintie 50
Oulu, 90029 OYS
Tampere University Hospital, ICU
Tampere, Pirkanmaa, 33521
About this study
Official title: A Prospective, Multi-centre, Randomised, Double-blind Comparison of Intravenous Dexmedetomidine With Midazolam for Continuous Sedation of Ventilated Patients in Intensive Care Unit
Patients in ICU who need help with their breathing are put onto a machine called a ventilator and are also given a medicine, called a sedative, which helps them to sleep and makes them more comfortable. Midazolam is a sedative that is routinely used for these purposes.
For most patients the aim of sedation is to make them sleepy but still able to respond to nursing staff (light sedation)
Read more
Dexmedetomidine is a new sedative for use in intensive care and in this clinical study, dexmedetomidine is compared to midazolam. It is thought that dexmedetomidine might be slightly better at allowing patients to be sleepy but still respond to people around them. It also does not appear to affect patient's breathing. the purpose of this study is to test whether dexmedetomidine really does have these advantages compared to midazolam.
in this study we hope to show that: dexmedetomidine is at least as good as midazolam in helping patients to sleep better and making them more comfortable, and that they are able to co-operate better with the staff treating them, and that patients treated with dexmedetomidine require a shorter time on the ventilator than those treated with midazolam.
Read the detailed description
This is a phase III, multi-centre, prospective, randomised, double-blind, double-dummy, active comparator study. The study consists of three periods: screening, double-dummy treatment and follow-up period.
All patients admitted to ICU will be pre-screened according to inclusion and exclusion criteria prior to informed consent using available clinical data.
Informed consent, screening and randomisation procedures should be completed within 72 hours from the time of admission to ICU and within 48 hours from starting continuous sedation. Eligible study subjects requiring light to moderate sedation (Richmond Agitation-Sedation Scale [RASS] = 0 to -3) will be randomised to either continue on midazolam or switch to dexmedetomidine. Patients should not have received any other continuously or regularly administered sedative agent than midazolam infusion during the last 12 hours except for opioid analgesics. Study treatments will be titrated to achieve an individually targeted sedation range determined on a daily basis. Rescue treatment (i.e. propofol boli) may be given if needed to achieve the target depth of sedation. Continued need for sedation will be assessed at a daily sedation stop, conducted at the same time each day. First sedation stop may be 12-36 hours from randomisation, depending on the time of day the study subject is randomised. The duration of study treatment is limited to a maximum of 14 days from randomisation. Following withdrawal of sedation, study subjects will be monitored for 48 hours and contacted by telephone 31 and 45 days after randomisation.
- Being tested
- Dexmedetomidine, Midazolam
- Keywords
- Initial Sedation, Mechanical ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Continuous Infusion
MidazolamDrug
Continuous Infusion
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Dexmedetomidine Receives: Drug: Dexmedetomidine |
| 2 | Active comparator | Midazolam Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depth of sedation using the RASS. The target RASS range (target depth of sedation) should be 0 to -3 for a patient to be included in the study. The target may be amended during the study treatment, if clinically required
Measured: RASS score will be assessed approximately 2 hourly during the treatment period and during the 48-hour follow-up period
Duration of mechanical ventilation the number of days the patient receives mechanical ventilation will be recorded
Measured: This variable will be dependent on the individual patient and the number of days they require mechanical ventilation .
Secondary outcomes (2)
Nurse's assessment of subject communication with visual analogue scales (VAS)Patients rousability and ability to co-operate and communicate will be measured using a visual analogue scale.
Measured: This will be measured at the end of every nursing shift whilst the patient remains on study treatment (maximum 14 days)
Length of ICU stay
Measured: Number of days a patient is in ICU which will vary depending on the underlying illness of the patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2007 (estimated)
- Study startJun 2007
- Primary completionAug 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Continuous Sedation in Initially Sedated Adults in ICUStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 501 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orion Corporation, Orion Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephan Jakob, MD PhD, Principal investigator, Insel Spital, Bern CH-3010 SwitzerlandAngela Ruck, BSc PhD, Study director, Orion Pharma R&D Nottingham England
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00481312
- Sponsor's protocol ID
- 3005013
- Acronym
- MIDEX
- Status last verified
- Nov 2009
- First submitted
- 31 May 2007
- Last updated
- 7 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Turunen H, Jakob SM, Ruokonen E, Kaukonen KM, Sarapohja T, Apajasalo M, Takala J. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care. 2015 Feb 19;19(1):67. doi: 10.1186/s13054-015-0787-y.
PubMed 25887576Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304.
PubMed 22436955
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-centre, Randomised, Double-blind Comparison of Intravenous Dexmedetomidine With Midazolam for Continuous Sedation of Ventilated Patients in Intensive Care Unit
- ClinicalTrials.gov ID
- NCT00481312
- Acronym / sponsor ID
- MIDEX / 3005013
- Keywords
- Initial Sedation, Mechanical ventilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 501 participants (actual)
- Lead sponsor
- Orion Corporation, Orion PharmaIndustry (pharma, biotech, devices)
- Study start
- Jun 2007
- Primary completion
- Aug 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 1 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients in ICU who need help with their breathing are put onto a machine called a ventilator and are also given a medicine, called a sedative, which helps them to sleep and makes them more comfortable. Midazolam is a sedative that is routinely used for these purposes.
For most patients the aim of sedation is to make them sleepy but still able to respond to nursing staff (light sedation)
Dexmedetomidine is a new sedative for use in intensive care and in this clinical study, dexmedetomidine is compared to midazolam. It is thought that dexmedetomidine might be slightly better at allowing patients to be sleepy but still respond to people around them. It also does not appear to affect patient's breathing. the purpose of this study is to test whether dexmedetomidine really does have these advantages compared to midazolam.
in this study we hope to show that: dexmedetomidine is at least as good as midazolam in helping patients to sleep better and making them more comfortable, and that they are able to co-operate better with the staff treating them, and that patients treated with dexmedetomidine require a shorter time on the ventilator than those treated with midazolam.
Detailed description
This is a phase III, multi-centre, prospective, randomised, double-blind, double-dummy, active comparator study. The study consists of three periods: screening, double-dummy treatment and follow-up period.
All patients admitted to ICU will be pre-screened according to inclusion and exclusion criteria prior to informed consent using available clinical data.
Informed consent, screening and randomisation procedures should be completed within 72 hours from the time of admission to ICU and within 48 hours from starting continuous sedation. Eligible study subjects requiring light to moderate sedation (Richmond Agitation-Sedation Scale [RASS] = 0 to -3) will be randomised to either continue on midazolam or switch to dexmedetomidine. Patients should not have received any other continuously or regularly administered sedative agent than midazolam infusion during the last 12 hours except for opioid analgesics. Study treatments will be titrated to achieve an individually targeted sedation range determined on a daily basis. Rescue treatment (i.e. propofol boli) may be given if needed to achieve the target depth of sedation. Continued need for sedation will be assessed at a daily sedation stop, conducted at the same time each day. First sedation stop may be 12-36 hours from randomisation, depending on the time of day the study subject is randomised. The duration of study treatment is limited to a maximum of 14 days from randomisation. Following withdrawal of sedation, study subjects will be monitored for 48 hours and contacted by telephone 31 and 45 days after randomisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: DexmedetomidineDexmedetomidine |
| 2 | Active comparator | Drug: MidazolamMidazolam |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 years and over
- Clinical need for sedation of an initially intubated (or tracheotomised) and ventilated (with inspiratory assistance) patient
- Prescribed light to moderate sedation (target RASS = 0 to -3) using midazolam infusion
- Patients should be randomised within 72 hours from ICU admission and within 48 hours of commencing continuous sedation in the ICU
- Patients should have an expected requirement for sedation of at least 24 hours from time of randomisation
Key exclusion criteria (20 listed)
- Acute severe intracranial or spinal neurological disorder due to vascular causes, infection, intracranial expansion or injury
- Uncompensated acute circulatory failure at time of randomisation (severe hypotension with MAP < 55 mmHg despite volume and pressors)
- Severe bradycardia (HR < 50 beats/min)
- AV-conduction block II-III (unless pacemaker installed)
- Severe hepatic impairment (bilirubin > 101 µmol/L)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineContinuous Infusion | Drug | 1 |
| MidazolamContinuous Infusion | Drug | 2 |
Primary outcome
Depth of sedation using the RASS. The target RASS range (target depth of sedation) should be 0 to -3 for a patient to be included in the study. The target may be amended during the study treatment, if clinically required
Time frame: RASS score will be assessed approximately 2 hourly during the treatment period and during the 48-hour follow-up period
Duration of mechanical ventilation the number of days the patient receives mechanical ventilation will be recorded
Time frame: This variable will be dependent on the individual patient and the number of days they require mechanical ventilation .
2 secondary outcomes
Nurse's assessment of subject communication with visual analogue scales (VAS)Patients rousability and ability to co-operate and communicate will be measured using a visual analogue scale.
Time frame: This will be measured at the end of every nursing shift whilst the patient remains on study treatment (maximum 14 days)
Length of ICU stay
Time frame: Number of days a patient is in ICU which will vary depending on the underlying illness of the patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2012.
- Derived from this study: PubMed 25887576Turunen H, Jakob SM, Ruokonen E, Kaukonen KM, Sarapohja T, Apajasalo M, Takala J. Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation. Crit Care. 2015 Feb 19;19(1):67. doi: 10.1186/s13054-015-0787-y.
- Derived from this study: PubMed 22436955Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan Jakob, MD PhD principal investigator
Insel Spital, Bern CH-3010 Switzerland
Angela Ruck, BSc PhD study director
Orion Pharma R&D Nottingham England
43 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexmedetomidine and Midazolam in people with Continuous Sedation in Initially Sedated Adults in ICU, run by Orion Corporation, Orion Pharma at 43 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in France, Netherlands, Belgium, Estonia, Norway and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depth of sedation using the RASS. The target RASS range (target depth of sedation) should be 0 to -3 for a patient to be included in the study. The target may be amended during the study treatment, if clinically required (time frame: RASS score will be assessed approximately 2 hourly during the treatment period and during the 48-hour follow-up period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00481312, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2012.