Continuous Sedation in Initially Sedated Adults in ICUPhase 3ProdexNCT00479661
Dexmedetomidine Versus Propofol for Continuous Sedation in the Intensive Care Unit (ICU)
A Phase 3 study testing Dexmedetomidine and Propofol in people with Continuous Sedation in Initially Sedated Adults in ICU, run by Orion Corporation, Orion Pharma at 40 sites in 7 countries.
Trial summary
Patients in the 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. Propofol 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 Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 40 sitesin 7 countries
- Study dates
- May 2007to Mar 2010
- 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 more than 18 years
- 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 propofol
- 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 more than 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 mean arterial pressure [MAP] < 55 mmHg despite volume and pressors)
- Severe bradycardia (heart rate [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 19Show 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
- 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 who are 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
40 sites in 7 countries.
40 sites in 7 countries
Germany12 sites
Charite Berlin Klinik fur Anasthesiologie und Operative Intensivmedizin (CCM), Luisenstrasse 65 (LU 65),
Berlin, 10117
Universitatsklinikum Bonn, Klinik u. Poliklinik f. Anasthesiologie u.
Bonn, 53105
Universitatsklinikum, Krankenhausstrsse 12,
Erlangen, 91054
Klinikum der Johann-Wolfgang-Goethe Universitat, Klinik fur Anasthesiologie,
Frankfurt am Main, 60590
Univ. Giessen und Marburg Abt. Anaesthesiologie, Intensivmedizin, Schmerztherapie & Palliativmedizin, Rudolf-Buchheim-Strasse 7,
Giessen, 35392
Universitatsklinikum Halle, Universitatsklinik fur Anasthelsiologie und Operative Intensivmedizin, Ernst-Grube Strasse 40
Halle, 06097
Universitatsklinikum Heidelberg Klinik fur Anasthesiologie, Im Neuenheimer Feld 110,
Heidelberg, 69120
Klinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, Universitatsklinikum des Saarlandes, Gebaude 57,
Homburg, 66421
Universitatsklinikum Leipzig, Klinik und Poliklinik fur Anaesthesiologie und Intensivtherapie, Liebigstrasse 29
Leipzig, 04103
Klinikum St. Georg, Delitzscher Strasse 141, Hause 20, 1. Etage, Zimmer 204
Leipzig, 04129
Universitatsklinikum Tubingen, Klinik fur Anasthesiologie und Intensivmedizin
Tübingen, 72076
Klinikum-Wetzlar-Braunfels, Forsthaus Strasse 1-3a
Wetzlar, 35578
Finland8 sites
HUCH, Jorvi Hospital, Turuntie 150,
Espoo, 02740
HUCH, Meilahti Hospital, Haartmaninkatu 4, P.O.Box 340,
Helsinki, 00029
North Carelia Central Hospital, Tikkamaentie 16,
Joensuu, 80210
Kuopio University Hospital
Kuopio, 70210
Paijat-Hame Central Hospital, Keskussairaalankatu 7,
Lahti, 15850
South Carelia Central Hospital, Valto Kakelan katu 1,
Lappeenranta, 53130
Seinajoki Central Hospital, Hanneksenrinne 7,
Seinäjoki, 60220
Tampere University Hospital, ICU, Teiskonntie 35, P.O.Box 2000,
Tampere, 33521
Russia7 sites
Kemerovo Stte Medical Academy, 22/A Voroshilov Street
Kemerovo, 650026
Municipal Hospital #2, Krasnodar Diversified Treatment and Diagnostic Association, 6, Ulica Krasnykh Partizan Building 2,
Krasnodar, 350012
Federal State Institution Russian Centre of Functional Surgical Gastroenterology, Krasnodor Municipal Hospital, 4, ulica Sedina,
Krasnodar, 350086
State Institution B.B. Petrovsky Russian Research Centre of Surgery of RAMS, 2, Abrikosovsky per.
Moscow, 119992
State Healthcare Institution V.A. Baranov Republican Hospital, 3, Pirogova Ulica,
Petrozavodsk, 185019
Medical Academy of Postgraduate Study, 41, ulica Kirochnaya,
Saint Petersburg, 191015
Federal State Healthcare Institution L.G. Sokolov Clinical Hospital, #122 of FMBA of Russia, 4, pr-t Kultury
Saint Petersburg, 194291
United Kingdom7 sites
West Suffolk Hospital NHS Trust, Hardwick Lane, Suffolk,
Bury St Edmunds, IP33 2QZ
Edinburgh University, Little France Crescent, Edinburgh Royal Infirmary,
Edinburgh, EH16 2SA
Leeds General Infirmary, Great George Street
Leeds, LS1 3EX
Saint John's Hospital, Howden Road West,
Livingston, EH54 6PP
Saint Thomas Hospital, Lambeth Palace Road,
London, SE1 7EH
Saint George's Hospital, Blackshaw Road, Tooting
London, SW17 0QT
Freeman Hospital, Freeman Road High Heaton,Newcastle Upon Tyne
Tyne and Wear, NE7 7DN
Netherlands3 sites
Jeroen Bosch Ziekenhuis, Postbus 90153,
's-Hertogenbosch, 5200 ME
Westfries Gasthuis, Department Intensieve Zorgen, Maelsonstraat 3,
Hoorn, 1624 NP
Rivierenland Hospital, Pres. Kennedylaan 1,
Tiel, 4001 WP
Belgium2 sites
Onze-Lieve-Vrouw Ziekenhuis, Anesthesia and Intensive Care Dept. Moorselbaan 164
Aalst, 9300
Ziekenhuis Oost-Limburg Location Sint-Jan, Dept.of Anesthesiology, Schiepse Bos
Genk, 3600
About this study
Official title: A Prospective, Multi-centre, Randomised, Double-blind Comparison of Intravenous Dexmedetomidine With Propofol for Continuous Sedation of Ventilated Patients in Intensive Care Unit
Patients in the 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. Propofol 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 propofol. 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 propofol.
In this study, we hope to show that: dexmedetomidine is at least as good as propofol in helping patients to sleep better and making them more comfortable, and that they are able to communicate and cooperate better with the staff treating them, and that patients treated with dexmedetomidine require a shorter time on the ventilator than those treated with propofol.
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 propofol or switch to dexmedetomidine. Patients should not have received any other continuously or regularly administered sedative agent than propofol 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. midazolam 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, Propofol
- 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
PropofolDrug
Continuous infusion
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Dexmedetomidine Receives: Drug: Dexmedetomidine |
| 2 | Active comparator | Propofol Receives: Drug: Propofol |
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: 2 hourly and before each rescue treatment dose during the treatment period and the 48-hour follow-up
Duration of mechanical ventilation
Measured: Start and stop times of mechanical ventilation while the patient is treated in the ICU
Secondary outcomes (2)
Nurse's assessment of subject communication with visual analogue scales (VAS)
Measured: At the end of each nursing shift during study treatment and 48 h follow-up period in the ICU
Length of ICU stay
Measured: Admission and discharge dates and times during the current ICU treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2007 (estimated)
- Study startMay 2007
- Primary completionMar 2010
- Study completionMar 2010
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orion Corporation, Orion Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Esko Ruokonen, MD, Principal investigator, Kuopio University HospitalKati Kaijasilta, MSc (Pharm), Study director, Orion Corporation, Orion Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00479661
- Sponsor's protocol ID
- 3005012
- Other IDs
- EudraCT 2006-006030-17
- Acronym
- Prodex
- Status last verified
- Aug 2010
- First submitted
- 25 May 2007
- Last updated
- 13 Aug 2010
- 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 13 Aug 2010. 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 Propofol for Continuous Sedation of Ventilated Patients in Intensive Care Unit
- ClinicalTrials.gov ID
- NCT00479661
- Acronym / sponsor ID
- Prodex / 3005012
- Keywords
- initial sedation, mechanical ventilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Orion Corporation, Orion PharmaIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 28 May 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 the 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. Propofol 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 propofol. 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 propofol.
In this study, we hope to show that: dexmedetomidine is at least as good as propofol in helping patients to sleep better and making them more comfortable, and that they are able to communicate and cooperate better with the staff treating them, and that patients treated with dexmedetomidine require a shorter time on the ventilator than those treated with propofol.
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 propofol or switch to dexmedetomidine. Patients should not have received any other continuously or regularly administered sedative agent than propofol 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. midazolam 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
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: DexmedetomidineDexmedetomidine |
| 2 | Active comparator | Drug: PropofolPropofol |
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 more than 18 years
- 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 propofol
- 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 more than 24 hours from time of randomisation
Key exclusion criteria (19 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 mean arterial pressure [MAP] < 55 mmHg despite volume and pressors)
- Severe bradycardia (heart rate [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 |
| PropofolContinuous 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: 2 hourly and before each rescue treatment dose during the treatment period and the 48-hour follow-up
Duration of mechanical ventilation
Time frame: Start and stop times of mechanical ventilation while the patient is treated in the ICU
2 secondary outcomes
Nurse's assessment of subject communication with visual analogue scales (VAS)
Time frame: At the end of each nursing shift during study treatment and 48 h follow-up period in the ICU
Length of ICU stay
Time frame: Admission and discharge dates and times during the current ICU treatment period
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 13 Aug 2010.
- 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.
Esko Ruokonen, MD principal investigator
Kuopio University Hospital
Kati Kaijasilta, MSc (Pharm) study director
Orion Corporation, Orion Pharma
40 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexmedetomidine and Propofol in people with Continuous Sedation in Initially Sedated Adults in ICU, run by Orion Corporation, Orion Pharma at 40 sites in 7 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 19 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 13 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Germany, Finland, Russia, United Kingdom, Netherlands and 2 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: 2 hourly and before each rescue treatment dose during the treatment period and the 48-hour follow-up). 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 NCT00479661, 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 13 Aug 2010.