Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Me-chanical Ventilation - Effects on Cognitive Function

• ClinicalTrials.gov Identifier: NCT02035436
• Recruitment Status: Completed
• First Posted: January 14, 2014
• Last Update Posted: March 15, 2019
• Sponsor: Palle Toft
• Collaborators: Kolding Sygehus; University of Southern Denmark; The Danish Council for Strategic Research
• Information provided by (Responsible Party): Palle Toft, Odense University Hospital

Study Description

Brief Summary:

Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level in these patients. The NONSEDA trial is an investigator-initiated, randomised, clinical, parallel-group, multinational, superiority trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden, comparing no sedation with sedation and a daily wake-up trial during mechanical ventilation. This is a substudy of the NONSEDA trial, concerning 250 patients included at trialsite Kolding, Denmark. The aim of the substudy is to assess the effects of no sedation on delirium during admission and cognitive function after discharge from ICU.

Our hypothesis is that critically ill patients who are not sedated during mechanical ventilation will have better cognitive function after discharge.

Condition or disease	Intervention/treatment	Phase
Delirium; Cognition Disorders	Other: Non-sedation; Other: Control: Sedation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Other
• Official Title: Substudy of the NONSEDA Trial (NCT01967680): Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Me-chanical Ventilation - Effects on Cognitive Function
• Actual Study Start Date: January 2014
• Actual Primary Completion Date: June 2017
• Actual Study Completion Date: March 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Non-sedation; Non-sedation supplemented with pain management during mechanical ventilation.	Other: Non-sedation; Patients are awake or have natural sleep during mechanical ventilation. Pain is treated with morphine iv.
Active Comparator: Sedation; Current gold standard: Sedation with a daily wake-up trial.	Other: Control: Sedation; Continuous iv-sedation (propofol first 48 hours, from then midazolam) to Ramsey 3-4 with a daily wake up attempt, where sedation is stopped until patient is awake.

Outcome Measures

Primary Outcome Measures :

1. Cognitive function [ Time Frame: 3 months after discharge from ICU ]

   Cognitive t-score, in percentage, difference between the two groups. The t-score for each patient will be diagnosed by the neuropsycologist at a personal interview and use of following tests:

   • Span of numbers
   • Coding test
   • Trailmaking A+B
   • Rey auditory verbal learning test (immediate, recall)
   • Rey-Ostherrieth complex figure test (immediate, recall, recognition)
   • Word finding test (S-word, animals)
   • Stroop test (congruent+incongruent)

Secondary Outcome Measures :

1. Attention/concentration [ Time Frame: 3 months after discharge from ICU ]
   T-score in the two groups for the cognitive domaine attention/concentration
2. Learning/memory [ Time Frame: 3 months after discharge from ICU ]
   t-score in the two groups for the cognitive domaine: learning/memory
3. Executive dysfunction [ Time Frame: 3 months after discharge from ICU ]
   t-score in the two groups for the cognitive domaine: executive dysfunction
4. Mental pace [ Time Frame: 3 months after discharge from ICU ]
   t-score in the two groups for the cognitive domaine: mental pace
5. Hypoactive delirium [ Time Frame: 3 months after discharge from ICU ]
   Occurrence of hypoactive delirium (RASS ≤ 0, CAM-ICU positive) in each group related to cognitive function at follow up
6. Agitated delirium [ Time Frame: 3 months after discharge from ICU ]
   Occurrence of agitated delirium (RASS ≥ +2, CAM-ICU positive) in each group related to cognitive function at follow up

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Endotracheally intubated
• Expected time on ventilator > 24 hours
• Age ≥ 18 years
• Informed consent

Exclusion Criteria:

• Severe head trauma where therapeutic coma is indicated
• Therapeutic hypothermia where therapeutic coma is indicated
• Status epilepticus where therapeutic coma is indicated
• Patient has participated in the study before
• Patient is transferred from another ICU with length of stay > 48 hours
• Patient is comatose at admission
• PaO2/FiO2 ≤ 9, if sedation is necessary for oxygenation
• Patient does not speak Danish, swedish or norwegian at a reasonable level

Contacts and Locations

Locations

Denmark

Lillebaelt Hospital, Kolding, Intensive Care Unit

Kolding, Denmark, 6000

Sponsors and Collaborators

Palle Toft

Kolding Sygehus

University of Southern Denmark

The Danish Council for Strategic Research

Investigators

• Principal Investigator: Helene Joergensen, MD; Lillebaelt Hospital, Kolding

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nedergaard HK, Jensen HI, Stylsvig M, Lauridsen JT, Toft P. Non-sedation versus sedation with a daily wake-up trial in critically ill patients recieving mechanical ventilation - effects on long-term cognitive function: Study protocol for a randomized controlled trial, a substudy of the NONSEDA trial. Trials. 2016 Jun 1;17(1):269. doi: 10.1186/s13063-016-1390-5.

• Responsible Party: Palle Toft, Professor, Odense University Hospital
• ClinicalTrials.gov Identifier: NCT02035436
• Other Study ID Numbers: S-20130025c
• First Posted: January 14, 2014
• Last Update Posted: March 15, 2019
• Last Verified: March 2019

Keywords provided by Palle Toft, Odense University Hospital:

Respiration, artificial; Critcal care

Additional relevant MeSH terms:

Delirium; Cognition Disorders; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders