Critical IllnessPhase 3NCT01360346
Enteral Versus Intravenous Sedation in Critically Ill High-risk ICU Patients
A Phase 3 study testing Enteral Sedation (EN) in people with Critical Illness and Mechanical Ventilation Complication, run by University of Milan at 1 site in Italy.
Trial summary
Recent studies suggest the employment of 'conscious' sedation (1) for critically high - risk patients (2), showing more efficacy then deep sedation (3). The investigators want to compare intravenous injection versus enteral sedative drugs administration, purposing to maintain a 'conscious' sedation level compatibly… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Mechanical Ventilation Complication
- What is being tested?
- Enteral Sedation (EN)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2012to Dec 2012
- 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
- High Risk Patients (Ventilation days assessment >3, SAPS II >32).
- Until 24 h after ICU admission
- Age > 18 years
Who cannot join
- Neurosurgical patients
- Allergy to medications used in the study
- CNS diseases (epilepsy, ictus, dementia, anoxic coma…)
- Liver encephalopathy (Child C)
- Previous psychiatric or cognitive pathology
- Absolute contraindications to use enteral route (acceptable NGT, digiunostomy, ileostomy)
- Pregnant patients or in breast-feeding
- DNR patients
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
AO San Paolo - Polo Universitario
Milan, 20142
Giovanni Mistraletti, MD, +39.339.8245014, giovanni.mistraletti@unimi.it
About this study
Official title: Multicentric, Single Blind, Randomized Controlled Trial on Enteral Sedation Versus Intravenous Sedation in Critically Ill High-risk ICU Patients
Recent studies suggest the employment of 'conscious' sedation (1) for critically high - risk patients (2), showing more efficacy then deep sedation (3). The investigators want to compare intravenous injection versus enteral sedative drugs administration, purposing to maintain a 'conscious' sedation level compatibly with the needed cares, invasive procedures, and medical and nursing surveillance.
Read the detailed description
Recent studies suggest the employment of 'conscious' sedation for critically high - risk patients (2), showing more efficacy then deep sedation (3). From this point of view it's important to consider both the choice of sedative drugs and the way to administer them to maintain the constant 'conscious' sedation level that the investigators wanted.
This research compares two different procedures for sedation therapy: through a randomized and blind controlled trial the interventional group will collect patients receiving sedatives from enteral way (4, 5, 6). In the control arm, sedation administration forecasts intravenous injection (7), recognised like the best practice in the most of intensive care units of the world.
To consider two different clinical approach for administration the investigators have to use different molecules: in the control arm propofol and midazolam will be continuously administered through intravenous injection with daily suspension (7); in the intervention arm the investigators will administer melatonin like a physiological hypnotic inductor (6), the continuous 'conscious' sedation will be maintained through hydroxyzine and eventually lorazepam (4), and all the active principles will be given by enteral administration.
The goal of the study is to compare intravenous injection versus enteral sedative drugs administration, analysing their efficacy and the feasibility to maintain constant the appropriate sedation level (RASS measured = RASS wished ±1) (8) in high - risk patients admitted in Intensive Care Unit (2), purposing to conserve a 'conscious' sedation level compatibly with the needed cares, invasive procedures, and medical and nursing surveillance.
MATERIALS AND METHODS Prospective, randomized and controlled multicentric, single blind trial. Participant ICU centres: San Paolo MI (Iapichino), Policlinico MI (Gattinoni) , Fatebenefratelli MI (Cigada), Niguarda MI (De Gasperi), Desio (Ronzoni), Legnano (Radrizzani), Monza (Pesenti), Belluno (Mazzon), Lugano (Malacrida), Modena (Rambaldi), Torino (Livigni), Asti (Cardellino).
PROCEDURE Bare minimum sedation drug titration will be done to maintain and to achieve prematurely a 'conscious' sedation level (RASS=0). During every shift it will be discussed the appropriate sedation therapy: if physicians choose a deep sedation goal (RASS <-3) this decision has to be explained and registered; then enteral sedation has to be maximized in randomized enteral patients group. If necessary intravenous sedation has to be added , and this procedure dose not represent a violation of research protocol.
If there is pain (VNR>3 or BPS>6) it will be administrated analgesic therapy according to hospital guidelines bare minimum duration. The treatment of procedural pain will be applied both groups trough Fentanest/Morphine + propofol/midazolam bolus intravenous, this procedure dose not represent a violation of research protocol.
If acute cerebral malfunction appears (CAM-ICU positive), it will be administrated haloperidol (1mg per os, max 10 mg/die) or other antipsychotic therapy according to hospital guidelines.
Enteral artificial nutrition with prokinetics will be started as soon as possible both group, while parenteral nutrition will be administered only if strictly necessary. If gastric stagnation > 200 ml/4 hours exceeds 2 days duration, it could be positioned nasogastric tube or digiunostomy.
All patients will be sit in a semiortopnoic position (bed back rest inclination between 30 and 45°).
STUDY POWER AND STATISTICAL ANALYSIS The investigators suppose to obtain a difference of 15% per cent between two arms for patients' sedation adequacy benefit (RASS = desired RASS + 1). Knowing that the enteral approach reached 83% adequacy from a observational monocentric research (5), it should be necessary to enrol 141 patients for each arm (power 80%). In consideration of the missing data, the investigators expect to enroll 300 patients. An "ad interim" statistical analysis is planned after the enrollment of 70 patients in each group.
To provide a statistical analysis as "Intention To Treat" for possible arms change risk.
It's planned to obtain a selective analysis involving each hospital included in the study.
It's planned to obtain a selective analysis about septic patients (greater delirium prevalence) (9).
It's planned to obtain a selective analysis divided for age (greater delirium prevalence if age >70) (10).
The randomization will be achieved trough out a particular Internet Website with a specific program expressly built. It will be used minimization technique to maintain groups balanced in the patients' sample of each centre.
- Being tested
- Enteral Sedation (EN), Control group: Intravenous Sedation (IV)
- Keywords
- Enteral Sedation, Intravenous Sedation, Critically ill ICU patient, Conscious Sedation, Deep Sedation, RASS, CAM-ICU, VNR, BPS, Propofol, Midazolam, Hydroxyzine, Lorazepam, Melatonin
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enteral Sedation (EN)Procedure or surgery
Also called ENTERAL
Intravenous propofol or midazolam administration at the ICU admission and stopped within 48h. Melatonin by enteral route (3mg x 2/die) from admission to discharge. Hydroxyzine by enteral route from ICU admission (600mg/die), decreased and stopped as soon as possible. Lorazepam supplementation (maximum 16mg/die) if hydroxyzine is inadequate.
Control group: Intravenous Sedation (IV)Procedure or surgery
Also called INTRAVENOUS
Propofol or midazolam from ICU admission to discharge at the compatible lowest level with harsh ICU environment.
| Study group | Role | What they receive |
|---|---|---|
| Enteral Sedation (EN) | Experimental | Melatonin, Hydroxyzine, and Lorazepam. At every work shift, it will be checked the possibility to decrease the Lorazepam and then the Hydroxyzine dosage to quickly obtain and continuously maintain a RASS level = 0 Receives: Procedure: Enteral Sedation (EN) |
| Intravenous Sedation (IV) | Active comparator | Intravenous propofol or midazolam administration at the ICU admission to discharge at the compatible lowest level with harsh ICU environment. At every shift nurses are requested to give intravenous lowest dosage to obtain RASS=0 Receives: Procedure: Control group: Intravenous Sedation (IV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of efficacy, measured by observed RASS = desired RASS ± 1.
Measured: One year
Secondary outcomes (7)
Sedation protocol effectiveness: percentage of "protocol violation days" on the total of ICU days.
Measured: One year
Delirium and coma free days (respectively negative CAM-ICU and RASS > - 3 in all daily observations until 28° ICU day) (11)
Measured: One year
Ventilation free days (12)
Measured: One year
Nursing evaluation of sedation adequacy (communication skills, cooperation, environment tolerance) (13)
Measured: One year
Overall ICU and hospital mortality, absolute mortality after 1 year from ICU discharge.
Measured: 24 months
Sedative drugs costs.
Measured: One year
Indirect inefficacy markers
- Prevalence of 'dangerous episodes': self - extubation, removal of other invasive clinical instruments;
- Length of ICU and hospital stay
- Use of anti-psychotic drugs (indirect delirium marker)
- Other indicators of sedation failure: use of restraining therapies, antagonist administrations (fluamzenil - naloxone).
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2011 (estimated)
- Study startJan 2012
- Primary completionOct 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Collaborators
- Ospedale San Paolo, Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Azienda Ospedaliera San Gerardo di Monza, Azienda Ospedaliera Niguarda Cà Granda, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Fondazione IRCCS Policlinico San Matteo di Pavia, San Luigi Gonzaga Hospital, Ospedale S. Giovanni Bosco, Ospedale Cardinal Massaia, Azienda Ospedaliera, Ospedale Civile di Legnano, Nuovo Ospedale Civile S.Agostino Estense
- Responsible party
- Principal investigator, Giovanni Mistraletti, University of Milan
- Investigators
- Iapichino Gaetano, MD, Study chair, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01360346
- Sponsor's protocol ID
- SedaENvsIV
- Status last verified
- Apr 2012
- First submitted
- 20 May 2011
- Last updated
- 24 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80. doi: 10.1016/S0140-6736(09)62072-9. Epub 2010 Jan 29.
PubMed 20116842Iapichino G, Mistraletti G, Corbella D, Bassi G, Borotto E, Miranda DR, Morabito A. Scoring system for the selection of high-risk patients in the intensive care unit. Crit Care Med. 2006 Apr;34(4):1039-43. doi: 10.1097/01.CCM.0000206286.19444.40.
PubMed 16484895Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007 Apr;106(4):687-95; quiz 891-2. doi: 10.1097/01.anes.0000264747.09017.da.
PubMed 17413906Cigada M, Pezzi A, Di Mauro P, Marzorati S, Noto A, Valdambrini F, Zaniboni M, Astori M, Iapichino G. Sedation in the critically ill ventilated patient: possible role of enteral drugs. Intensive Care Med. 2005 Mar;31(3):482-6. doi: 10.1007/s00134-005-2559-7. Epub 2005 Feb 16.
PubMed 15714324Cigada M, Corbella D, Mistraletti G, Forster CR, Tommasino C, Morabito A, Iapichino G. Conscious sedation in the critically ill ventilated patient. J Crit Care. 2008 Sep;23(3):349-53. doi: 10.1016/j.jcrc.2007.04.003. Epub 2007 Jul 5.
PubMed 18725039Mistraletti G, Sabbatini G, Taverna M, Figini MA, Umbrello M, Magni P, Ruscica M, Dozio E, Esposti R, DeMartini G, Fraschini F, Rezzani R, Reiter RJ, Iapichino G. Pharmacokinetics of orally administered melatonin in critically ill patients. J Pineal Res. 2010 Mar;48(2):142-7. doi: 10.1111/j.1600-079X.2009.00737.x. Epub 2010 Jan 8.
PubMed 20070489Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34. doi: 10.1016/S0140-6736(08)60105-1.
PubMed 18191684Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138.
PubMed 12421743Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38. doi: 10.1186/cc8916. Epub 2010 Mar 16.
PubMed 20233428Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available.
PubMed 16540616Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007 Dec 12;298(22):2644-53. doi: 10.1001/jama.298.22.2644.
PubMed 18073360Schoenfeld DA, Bernard GR; ARDS Network. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med. 2002 Aug;30(8):1772-7. doi: 10.1097/00003246-200208000-00016.
PubMed 12163791Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.
PubMed 19188334Mistraletti G, Umbrello M, Salini S, Cadringher P, Formenti P, Chiumello D, Villa C, Russo R, Francesconi S, Valdambrini F, Bellani G, Palo A, Riccardi F, Ferretti E, Festa M, Gado AM, Taverna M, Pinna C, Barbiero A, Ferrari PA, Iapichino G; SedaEN investigators. Enteral versus intravenous approach for the sedation of critically ill patients: a randomized and controlled trial. Crit Care. 2019 Jan 7;23(1):3. doi: 10.1186/s13054-018-2280-x.
PubMed 30616675Mistraletti G, Mantovani ES, Cadringher P, Cerri B, Corbella D, Umbrello M, Anania S, Andrighi E, Barello S, Di Carlo A, Martinetti F, Formenti P, Spanu P, Iapichino G; SedaEN investigators. Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial. Trials. 2013 Apr 3;14:92. doi: 10.1186/1745-6215-14-92.
PubMed 23551983
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentric, Single Blind, Randomized Controlled Trial on Enteral Sedation Versus Intravenous Sedation in Critically Ill High-risk ICU Patients
- ClinicalTrials.gov ID
- NCT01360346
- Acronym / sponsor ID
- SedaENvsIV
- Keywords
- Enteral Sedation, Intravenous Sedation, Critically ill ICU patient, Conscious Sedation, Deep Sedation, RASS, CAM-ICU, VNR
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Collaborators
- Ospedale San Paolo, Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Azienda Ospedaliera San Gerardo di Monza, Azienda Ospedaliera Niguarda Cà Granda, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Fondazione IRCCS Policlinico San Matteo di Pavia, San Luigi Gonzaga Hospital, Ospedale S. Giovanni Bosco, Ospedale Cardinal Massaia, Azienda Ospedaliera, Ospedale Civile di Legnano, Nuovo Ospedale Civile S.Agostino Estense
- Study start
- Jan 2012
- Primary completion
- Oct 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 25 May 2011 (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.
Recent studies suggest the employment of 'conscious' sedation (1) for critically high - risk patients (2), showing more efficacy then deep sedation (3). The investigators want to compare intravenous injection versus enteral sedative drugs administration, purposing to maintain a 'conscious' sedation level compatibly with the needed cares, invasive procedures, and medical and nursing surveillance.
Detailed description
Recent studies suggest the employment of 'conscious' sedation for critically high - risk patients (2), showing more efficacy then deep sedation (3). From this point of view it's important to consider both the choice of sedative drugs and the way to administer them to maintain the constant 'conscious' sedation level that the investigators wanted.
This research compares two different procedures for sedation therapy: through a randomized and blind controlled trial the interventional group will collect patients receiving sedatives from enteral way (4, 5, 6). In the control arm, sedation administration forecasts intravenous injection (7), recognised like the best practice in the most of intensive care units of the world.
To consider two different clinical approach for administration the investigators have to use different molecules: in the control arm propofol and midazolam will be continuously administered through intravenous injection with daily suspension (7); in the intervention arm the investigators will administer melatonin like a physiological hypnotic inductor (6), the continuous 'conscious' sedation will be maintained through hydroxyzine and eventually lorazepam (4), and all the active principles will be given by enteral administration.
The goal of the study is to compare intravenous injection versus enteral sedative drugs administration, analysing their efficacy and the feasibility to maintain constant the appropriate sedation level (RASS measured = RASS wished ±1) (8) in high - risk patients admitted in Intensive Care Unit (2), purposing to conserve a 'conscious' sedation level compatibly with the needed cares, invasive procedures, and medical and nursing surveillance.
MATERIALS AND METHODS Prospective, randomized and controlled multicentric, single blind trial. Participant ICU centres: San Paolo MI (Iapichino), Policlinico MI (Gattinoni) , Fatebenefratelli MI (Cigada), Niguarda MI (De Gasperi), Desio (Ronzoni), Legnano (Radrizzani), Monza (Pesenti), Belluno (Mazzon), Lugano (Malacrida), Modena (Rambaldi), Torino (Livigni), Asti (Cardellino).
PROCEDURE Bare minimum sedation drug titration will be done to maintain and to achieve prematurely a 'conscious' sedation level (RASS=0). During every shift it will be discussed the appropriate sedation therapy: if physicians choose a deep sedation goal (RASS <-3) this decision has to be explained and registered; then enteral sedation has to be maximized in randomized enteral patients group. If necessary intravenous sedation has to be added , and this procedure dose not represent a violation of research protocol.
If there is pain (VNR>3 or BPS>6) it will be administrated analgesic therapy according to hospital guidelines bare minimum duration. The treatment of procedural pain will be applied both groups trough Fentanest/Morphine + propofol/midazolam bolus intravenous, this procedure dose not represent a violation of research protocol.
If acute cerebral malfunction appears (CAM-ICU positive), it will be administrated haloperidol (1mg per os, max 10 mg/die) or other antipsychotic therapy according to hospital guidelines.
Enteral artificial nutrition with prokinetics will be started as soon as possible both group, while parenteral nutrition will be administered only if strictly necessary. If gastric stagnation > 200 ml/4 hours exceeds 2 days duration, it could be positioned nasogastric tube or digiunostomy.
All patients will be sit in a semiortopnoic position (bed back rest inclination between 30 and 45°).
STUDY POWER AND STATISTICAL ANALYSIS The investigators suppose to obtain a difference of 15% per cent between two arms for patients' sedation adequacy benefit (RASS = desired RASS + 1). Knowing that the enteral approach reached 83% adequacy from a observational monocentric research (5), it should be necessary to enrol 141 patients for each arm (power 80%). In consideration of the missing data, the investigators expect to enroll 300 patients. An "ad interim" statistical analysis is planned after the enrollment of 70 patients in each group.
To provide a statistical analysis as "Intention To Treat" for possible arms change risk.
It's planned to obtain a selective analysis involving each hospital included in the study.
It's planned to obtain a selective analysis about septic patients (greater delirium prevalence) (9).
It's planned to obtain a selective analysis divided for age (greater delirium prevalence if age >70) (10).
The randomization will be achieved trough out a particular Internet Website with a specific program expressly built. It will be used minimization technique to maintain groups balanced in the patients' sample of each centre.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enteral Sedation (EN) | Experimental | Procedure: Enteral Sedation (EN)Melatonin, Hydroxyzine, and Lorazepam. At every work shift, it will be checked the possibility to decrease the Lorazepam and then the Hydroxyzine dosage to quickly obtain and continuously maintain a RASS level = 0 |
| Intravenous Sedation (IV) | Active comparator | Procedure: Control group: Intravenous Sedation (IV)Intravenous propofol or midazolam administration at the ICU admission to discharge at the compatible lowest level with harsh ICU environment. At every shift nurses are requested to give intravenous lowest dosage to obtain RASS=0 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- High Risk Patients (Ventilation days assessment >3, SAPS II >32).
- Until 24 h after ICU admission
- Age > 18 years
Key exclusion criteria (8 listed)
- Neurosurgical patients
- Allergy to medications used in the study
- CNS diseases (epilepsy, ictus, dementia, anoxic coma…)
- Liver encephalopathy (Child C)
- Previous psychiatric or cognitive pathology
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 |
|---|---|---|
| Enteral Sedation (EN)Also: ENTERALIntravenous propofol or midazolam administration at the ICU admission and stopped within 48h. Melatonin by enteral route (3mg x 2/die) from admission to discharge. Hydroxyzine by enteral route from ICU admission (600mg/die), decreased and stopped as soon as possible. Lorazepam supplementation (maximum 16mg/die) if hydroxyzine is inadequate. | Procedure or surgery | Enteral Sedation (EN) |
| Control group: Intravenous Sedation (IV)Also: INTRAVENOUSPropofol or midazolam from ICU admission to discharge at the compatible lowest level with harsh ICU environment. | Procedure or surgery | Intravenous Sedation (IV) |
Primary outcome
Percent of efficacy, measured by observed RASS = desired RASS ± 1.
Time frame: One year
7 secondary outcomes
Sedation protocol effectiveness: percentage of "protocol violation days" on the total of ICU days.
Time frame: One year
Delirium and coma free days (respectively negative CAM-ICU and RASS > - 3 in all daily observations until 28° ICU day) (11)
Time frame: One year
Ventilation free days (12)
Time frame: One year
Nursing evaluation of sedation adequacy (communication skills, cooperation, environment tolerance) (13)
Time frame: One year
Overall ICU and hospital mortality, absolute mortality after 1 year from ICU discharge.
Time frame: 24 months
Sedative drugs costs.
Time frame: One year
Indirect inefficacy markers
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2012.
- Background: PubMed 20116842Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010 Feb 6;375(9713):475-80. doi: 10.1016/S0140-6736(09)62072-9. Epub 2010 Jan 29.
- Background: PubMed 16484895Iapichino G, Mistraletti G, Corbella D, Bassi G, Borotto E, Miranda DR, Morabito A. Scoring system for the selection of high-risk patients in the intensive care unit. Crit Care Med. 2006 Apr;34(4):1039-43. doi: 10.1097/01.CCM.0000206286.19444.40.
- Background: PubMed 17413906Payen JF, Chanques G, Mantz J, Hercule C, Auriant I, Leguillou JL, Binhas M, Genty C, Rolland C, Bosson JL. Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study. Anesthesiology. 2007 Apr;106(4):687-95; quiz 891-2. doi: 10.1097/01.anes.0000264747.09017.da.
- Background: PubMed 15714324Cigada M, Pezzi A, Di Mauro P, Marzorati S, Noto A, Valdambrini F, Zaniboni M, Astori M, Iapichino G. Sedation in the critically ill ventilated patient: possible role of enteral drugs. Intensive Care Med. 2005 Mar;31(3):482-6. doi: 10.1007/s00134-005-2559-7. Epub 2005 Feb 16.
- Background: PubMed 18725039Cigada M, Corbella D, Mistraletti G, Forster CR, Tommasino C, Morabito A, Iapichino G. Conscious sedation in the critically ill ventilated patient. J Crit Care. 2008 Sep;23(3):349-53. doi: 10.1016/j.jcrc.2007.04.003. Epub 2007 Jul 5.
- Background: PubMed 20070489Mistraletti G, Sabbatini G, Taverna M, Figini MA, Umbrello M, Magni P, Ruscica M, Dozio E, Esposti R, DeMartini G, Fraschini F, Rezzani R, Reiter RJ, Iapichino G. Pharmacokinetics of orally administered melatonin in critically ill patients. J Pineal Res. 2010 Mar;48(2):142-7. doi: 10.1111/j.1600-079X.2009.00737.x. Epub 2010 Jan 8.
- Background: PubMed 18191684Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34. doi: 10.1016/S0140-6736(08)60105-1.
- Background: PubMed 12421743Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138.
- Background: PubMed 20233428Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38. doi: 10.1186/cc8916. Epub 2010 Mar 16.
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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.
Iapichino Gaetano, MD study chair
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enteral Sedation (EN) in people with Critical Illness and Mechanical Ventilation Complication, run by University of Milan at 1 site in Italy.
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 3 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 24 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Mistraletti, MD (+39.339.8245014, giovanni.mistraletti@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of efficacy, measured by observed RASS = desired RASS ± 1. (time frame: One year). 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 NCT01360346, which also lists 15 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 24 Apr 2012; AzTrials last refreshed its copy on 8 Nov 2026.