Enteral Versus Intravenous Sedation in Critically Ill High-risk ICU Patients

NCT ID: NCT01360346

Last Updated: 2012-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2012-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Critical Illness Mechanical Ventilation Complication

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

Enteral Sedation (EN)

Intervention Type PROCEDURE

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.

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

Group Type ACTIVE_COMPARATOR

Control group: Intravenous Sedation (IV)

Intervention Type PROCEDURE

Propofol or midazolam from ICU admission to discharge at the compatible lowest level with harsh ICU environment.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Enteral Sedation (EN)

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.

Intervention Type PROCEDURE

Control group: Intravenous Sedation (IV)

Propofol or midazolam from ICU admission to discharge at the compatible lowest level with harsh ICU environment.

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ENTERAL INTRAVENOUS

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* High Risk Patients (Ventilation days assessment \>3, SAPS II \>32).
* Until 24 h after ICU admission
* Age \> 18 years

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Ospedale San Paolo

OTHER

Sponsor Role collaborator

Ospedale Maggiore Policlinico Mangiagalli e Regina Elena

OTHER

Sponsor Role collaborator

Azienda Ospedaliera San Gerardo di Monza

OTHER

Sponsor Role collaborator

Azienda Ospedaliera Niguarda Cà Granda

OTHER

Sponsor Role collaborator

Azienda Ospedaliera Fatebenefratelli e Oftalmico

OTHER

Sponsor Role collaborator

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role collaborator

San Luigi Gonzaga Hospital

OTHER

Sponsor Role collaborator

Ospedale S. Giovanni Bosco

OTHER

Sponsor Role collaborator

Ospedale Cardinal Massaia

OTHER

Sponsor Role collaborator

Azienda Ospedaliera, Ospedale Civile di Legnano

OTHER

Sponsor Role collaborator

Nuovo Ospedale Civile S.Agostino Estense

OTHER

Sponsor Role collaborator

University of Milan

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Giovanni Mistraletti

University Researcher

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Iapichino Gaetano, MD

Role: STUDY_CHAIR

University of Milan

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

AO San Paolo - Polo Universitario

Milan, , Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Giovanni Mistraletti, MD

Role: CONTACT

+39.339.8245014

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Giovanni Mistraletti, MD

Role: primary

+39.339.8245014

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 20116842 (View on PubMed)

Iapichino 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.

Reference Type BACKGROUND
PMID: 16484895 (View on PubMed)

Payen 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.

Reference Type BACKGROUND
PMID: 17413906 (View on PubMed)

Cigada 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.

Reference Type BACKGROUND
PMID: 15714324 (View on PubMed)

Cigada 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.

Reference Type BACKGROUND
PMID: 18725039 (View on PubMed)

Mistraletti 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.

Reference Type BACKGROUND
PMID: 20070489 (View on PubMed)

Girard 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.

Reference Type BACKGROUND
PMID: 18191684 (View on PubMed)

Sessler 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.

Reference Type BACKGROUND
PMID: 12421743 (View on PubMed)

Pandharipande 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.

Reference Type BACKGROUND
PMID: 20233428 (View on PubMed)

Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available.

Reference Type BACKGROUND
PMID: 16540616 (View on PubMed)

Pandharipande 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.

Reference Type BACKGROUND
PMID: 18073360 (View on PubMed)

Schoenfeld 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.

Reference Type BACKGROUND
PMID: 12163791 (View on PubMed)

Riker 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.

Reference Type BACKGROUND
PMID: 19188334 (View on PubMed)

Mistraletti 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.

Reference Type DERIVED
PMID: 30616675 (View on PubMed)

Mistraletti 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.

Reference Type DERIVED
PMID: 23551983 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

SedaENvsIV

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Ketamine Versus Propofol as ICU Sedation
NCT06243822 COMPLETED PHASE4
SEvoflurane for Sedation in ARds
NCT04235608 COMPLETED PHASE3