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

April 23, 2012 updated by: Giovanni Mistraletti, University of Milan

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy, 20142
        • Recruiting
        • AO San Paolo - Polo Universitario

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Procedure: 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.
Other Names:
  • ENTERAL
Active Comparator: 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
Procedure: Control group: Intravenous Sedation (IV)
Propofol or midazolam from ICU admission to discharge at the compatible lowest level with harsh ICU environment.
Other Names:
  • INTRAVENOUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent of efficacy, measured by observed RASS = desired RASS ± 1.
Time Frame: One year
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sedation protocol effectiveness: percentage of "protocol violation days" on the total of ICU days.
Time Frame: One year
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
One year
Ventilation free days (12)
Time Frame: One year
One year
Nursing evaluation of sedation adequacy (communication skills, cooperation, environment tolerance) (13)
Time Frame: One year
One year
Overall ICU and hospital mortality, absolute mortality after 1 year from ICU discharge.
Time Frame: 24 months
24 months
Sedative drugs costs.
Time Frame: One year
One year
Indirect inefficacy markers
Time Frame: One year
  1. Prevalence of 'dangerous episodes': self - extubation, removal of other invasive clinical instruments;
  2. Length of ICU and hospital stay
  3. Use of anti-psychotic drugs (indirect delirium marker)
  4. Other indicators of sedation failure: use of restraining therapies, antagonist administrations (fluamzenil - naloxone).
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Milan

Collaborators

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

Investigators

  • Study Chair: Iapichino Gaetano, MD, University of Milan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Anticipated)

October 1, 2012

Study Completion (Anticipated)

December 1, 2012

Study Registration Dates

First Submitted

May 20, 2011

First Submitted That Met QC Criteria

May 24, 2011

First Posted (Estimate)

May 25, 2011

Study Record Updates

Last Update Posted (Estimate)

April 24, 2012

Last Update Submitted That Met QC Criteria

April 23, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SedaENvsIV

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Critical Illness

Clinical Trials on Enteral Sedation (EN)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in India

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe