Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation

Critical Illness Clinical Trial

— NONSEDA  

Official title:

Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation. The NONSEDA-trial. An Investigator-initiated, Randomised, Clinical, Parallel-group, Multinational, Superiority Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01967680
• Other study ID #: S-20130025
• Status: Completed
• Phase: N/A
• First received: October 18, 2013
• Last updated: April 5, 2018
• Start date: January 2014
• Est. completion date: April 2018

Study information

• Verified date: April 2018
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: Every year 30,000 Danish patients are admitted to Intensive Care Units (ICU), accounting for 2-3% of all patients in hospital and 30% of the yearly hospital expenditure. The mortality in the ICU is 12.7 % and the 30-day mortality is 21.2 % according to the national Danish Intensive Care Database. Through many years, the standard care has been to use continuous sedation of critically ill patients during me-chanical ventilation. However, recent research indicates that it is beneficial to reduce the sedation level in these patients. A randomised trial found that continuous sedation with a daily wake-up trial compared to continuous sedation reduced the time on me-chanical ventilation and the length of stay in the intensive care unit. Further, a ran-domised trial comparing continuous sedation with a daily wake-up trial to no sedation found that patients in the non-sedated group needed mechanical ventilation for a shorter time and had a shorter length of stay in the ICU and in the hospital. The trial also indicated a beneficial effect on mortality, however the trial was not a priori de-signed or powered with respect to mortality. No randomised trial has been published comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.

Objective: To assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients in ICU.

Design: 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.

Inclusion criteria: Mechanically ventilated patients with expected duration of me-chanical ventilation > 24 hours.

Exclusion criteria: non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2<9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.

Experimental intervention: Non-sedation supplemented with pain management during mechanical ventilation.

Control intervention: Sedation with a daily wake-up trial.

The primary hypothesis is that non-sedation compared to sedation and a daily wake-up trial will reduce mortality.

The secondary hypotheses are that non-sedation compared to sedation and a daily wake-up trial will:

• Reduce the incidence of a composite outcome of death, acute myocardial in-farction (AMI), stroke, pulmonary embolism and other thromboembolic events.

• Reduce the number of organ failures.

• Increase the days alive without mechanical ventilation.

• Increase the days alive outside the ICU.

• Increase the days alive outside the hospital.

Outcomes: The primary outcome is all-cause mortality at 90 days. Secondary out-comes are time to death in the trial period, the frequency of the trombo-embolic com-plications, acute renal failure, days alive without mechanical ventilation, days alive outside the ICU and hospital. Explorative outcomes are mortality at 28 days, organ failure and coma-free, delirium-free days.

Trial size: The investigators will include 700 participants (2 x 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Endotracheally intubated Expected time on ventilator > 24 h. 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

Related Conditions & MeSH terms

• Critical Illness
• Respiration, Artificial

Intervention

Procedure:
• Non-sedation for intubated, mechanically ventilated patients

• Controlgroup, sedation with daily wake-up trial

Locations

Country	Name	City	State
Denmark	AArhus university Hospital, Noerrebrogade	AArhus
Denmark	Sydvestjysk Sygehus	Esbjerg	Region Of Southern Denmark
Denmark	Kolding Hospital	Kolding
Denmark	Odense University Hospital	Odense
Denmark	Svendborg Hospital	Svendborg
Norway	Vestfold Hospital	Tonsberg
Norway	University Hospital of North Norway	Tromsoe
Sweden	Linkjøbing University Hospital	Linkoping

Sponsors (3)

Lead Sponsor	Collaborator
Palle Toft	Aase and Ejnar Danielsens Foundation, The Danish Medical Research Council

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

References & Publications (1)

Strøm 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	All cause mortality at 28 days after randomisation.	28 days
Other	Discharge fro ICU	Days until discharge from the intensive care unit (within 90 days from randomization)	90 days
Other	End of mechanical ventilation	Days until the participant is without without mechanical ventilation (within 90 days from randomization)	90 days
Other	Discharge from hospital	Days until discharge from the hospital (within 90 days from randomization).	90 days
Other	Number of organ failures	Organ failure when the patient is discharged from the ICU.	ICU-admission
Other	Accidental extubation	Number of accidental extubations requiring re-intubation within 1 hour	ICU-admission
Other	Accidental removal of cental venous line	Number of accidental removals of central venous lines, requiring re-insertion within 4 hours	ICU-admission
Other	Oxygenation	Worst oxygenation status measured by; highest fraction of oxygen in inspired air (FiO2); worst paO2/FiO2-ratio registered daily	During ventilator treatment
Other	1-year survival	Number of patients alive 1 year after randomisation in each group	1 year from randomisation
Primary	Mortality	All cause mortality at 90 days after randomization	90 days
Secondary	Days until death	Days until death throughout the total observation period	1 year
Secondary	Cardiovascular event	Proportion of participants with a major cardiovascular outcome (acute myocardial infarction, cerebral infarction, cerebral hemorrhage, pulmonary embolus, deep vein thrombosis, other thrombo-embolic event) at 90 days after randomization.	90 days
Secondary	Coma and deliriumfree days	Number of coma- and delirium-free days (defined as RASS = 3 and no positive CAM-ICU scorings the particular day) within 28 days from randomization	28 days
Secondary	RIFLE-score	Highest Rifle-score within 28 days from randomization (Rifle-categories: Rifle-R: Increase in serum creatinine x 1.5 from baseline OR urine output < 0.5 mL/kg/hr x 6 h.; Rifle-I: Increase in serum creatinine x 2 from baseline OR urine output < 0.5 mL/kg/hr x 12 h.; Rifle-F: Increase in serum creatinine x 3 from baseline OR urine output < 0.3 mL/kg/hr x 24h OR creatinine = 350µmol/L with acute rise = 44 µmol/L in < 24h)	28 days
Secondary	Days until discharge	Days until discharge from ICU (within 28 days from randomization).	28 days
Secondary	Days until the participant is without mechanical ventilation	Days until the participant is without mechanical ventilation (within 28 days from randomization).	28 days