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

NCT01360346 | Unknown Phase 3 DMC

• 1 other identifier: SedaENvsIV
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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 with the needed cares, invasive procedures, and medical and nursing surveillance.

Conditions

Critical Illness; Mechanical Ventilation Complication

Keywords

Enteral Sedation; Intravenous Sedation; Critically ill ICU patient; Conscious Sedation; Deep Sedation; RASS; CAM-ICU; VNR; BPS; Propofol; Midazolam; Hydroxyzine; Lorazepam; Melatonin

Outcome Measures

Primary Outcomes (1)

• Percent of efficacy, measured by observed RASS = desired RASS ± 1.

  One year

Secondary Outcomes (7)

• Sedation protocol effectiveness: percentage of "protocol violation days" on the total of ICU days.

  One year

• Delirium and coma free days (respectively negative CAM-ICU and RASS > - 3 in all daily observations until 28° ICU day) (11)

  One year

• Ventilation free days (12)

  One year

• Nursing evaluation of sedation adequacy (communication skills, cooperation, environment tolerance) (13)

  One year

• Overall ICU and hospital mortality, absolute mortality after 1 year from ICU discharge.

  24 months

Study Arms (2)

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

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

Procedure: Control group: Intravenous Sedation (IV)

Interventions

Enteral Sedation (EN) 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.

Also known as: ENTERAL

Enteral Sedation (EN)

Control group: Intravenous Sedation (IV) PROCEDURE

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

Also known as: INTRAVENOUS

Intravenous Sedation (IV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Milan: lead
• Ospedale San Paolo: collaborator
• Ospedale Maggiore Policlinico Mangiagalli e Regina Elena: collaborator
• Azienda Ospedaliera San Gerardo di Monza: collaborator
• Azienda Ospedaliera Niguarda Cà Granda: collaborator
• Azienda Ospedaliera Fatebenefratelli e Oftalmico: collaborator
• Fondazione IRCCS Policlinico San Matteo di Pavia: collaborator
• San Luigi Gonzaga Hospital: collaborator
• Ospedale S. Giovanni Bosco: collaborator
• Ospedale Cardinal Massaia: collaborator
• Azienda Ospedaliera, Ospedale Civile di Legnano: collaborator
• Nuovo Ospedale Civile S.Agostino Estense: collaborator

Study Sites (1)

AO San Paolo - Polo Universitario

Milan, 20142, Italy

RECRUITING

Related Publications (15)

• 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.

  PMID: 20116842 BACKGROUND

• 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.

  PMID: 16484895 BACKGROUND

• 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.

  PMID: 17413906 BACKGROUND

• 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.

  PMID: 15714324 BACKGROUND

• 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.

  PMID: 18725039 BACKGROUND

• 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.

  PMID: 20070489 BACKGROUND

• 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.

  PMID: 18191684 BACKGROUND

• 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.

  PMID: 12421743 BACKGROUND

• 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.

  PMID: 20233428 BACKGROUND

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

  PMID: 16540616 BACKGROUND

• 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.

  PMID: 18073360 BACKGROUND

• 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.

  PMID: 12163791 BACKGROUND

• 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.

  PMID: 19188334 BACKGROUND

• 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.

  PMID: 30616675 DERIVED

• 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.

  PMID: 23551983 DERIVED

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Iapichino Gaetano, MD

  University of Milan

  STUDY CHAIR

Central Study Contacts

Giovanni Mistraletti, MD

CONTACT

+39.339.8245014; giovanni.mistraletti@unimi.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: University Researcher

Study Record Dates

• First Submitted: May 20, 2011
• First Posted: May 25, 2011
• Study Start: January 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 24, 2012

Record last verified: 2012-04

Locations

IT (1)