NONSEDA-trial status November 2014

Thomas Strøm, MD, PhD Helene Korvenius Nedergaard, MD Hanne Tanghus Olsen, MD Palle Toft, Professor, DMsc Department of Intensive Care University Hospital University of Southern [email protected] I am not dead I am only

sleeping 2

Hans Christian Andersen 19th century Danish poet

17-11-2014

Number of ventilator free days in a 28 days period ICU length of stay (28 days) Total hospital length of stay (90 days) Do we need more evidence?

Richmond Agitation Sedation Scale (RASS)

0

-1

RASS -5 to +4to -5 RASS

-2

-3 1 2 3 4 5 6 7 day

No sedation (n=53) Sedation (n=58)

Laerkner, Stroem and Toft. In Press. NONSEDA-trial

An investigator-initiated, randomised, clinical, parallel- group, multinational, superiority trial

Financed by the Danish Strategic Research Council

ClinicalTrials.gov Identifier: NCT01967680 Design

Randomised, clinical, parallel-group, multinational, superiority trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden. Inclusion criteria

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

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

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

All-cause mortality at 90 days after randomization Secondary outcomes

• Proportion of patients with a major cardiovascular event within 90 days after randomisation. • Number of coma and delirium-free days within 28 days from randomisation • Highest Rifle-score within 28 days from randomization • Days until discharge from the intensive care unit within 28 days from randomisation. • Days until the participant is without mechanical ventilation within 28 days from randomisation. Sub-studies

Four sub-studies involving 250 patients from the main trial :

• Physical function • Cognitive function • Post-Traumatic Stress Disorder (PTSD) • Level of melatonin Site Investigators Denmark, Svendborg:*  Hanne Tanghus Olsen, MD, PhD-student. Department of Anaesthesiology and Intensive Care, Svendborg  Lone Juhl, RN Hospital, Odense University Hospital Denmark, Kolding:*  Helene Korvenius Jorgensen, MD, PhD-student. Department of Anaesthesiology and Intensive Care, Lillebaelt Hospital,  Trine Haberlandt, RN Kolding. Denmark, Aarhus:*  Helle Nibro, MD, PhD. Department of Anaesthesiology and Intensive Care, Aarhus University  Lasse Lundolm, RN Hospital, Aarhus Noerrebrogade. Denmark, Esbjerg:*  Jakob Oxlund, MD. Department of Anaesthesiology and Intensive Care, Esbjerg Hospital.  Randi Howard, RN Denmark, Odense:  Palle Toft, MD, professor, DMSc. Research unit, Department of Anaesthesiology and Intensive Care,  Thomas Strøm, MD, PhD, postdoc. Odense University Hospital. Denmark, Copenhagen:  Janus Christian Jakobsen, MD, PhD Copenhagen Trial Unit, Centre for Clinical Intervention Research,  Jørn Wetterslev, MD, PhD. Rigshospitalet, Copenhagen University Hospital  Jane Lindschou, Clinical Research Consultant, MSc. Norway, Tønsberg*:  Karl-André Wian, MD Department of Anaesthesiology and Intensive Care, Vestfold Hospital  Gro Aagaard, RN Tønsberg Norway, Tromsø*  Bjørn Anders Kroken, MD, PhD Department of Anaesthesiology and Intensive Care, Tromsø University  Inga Akeren, RN Hospital

Sweden, Halmstad*:  Michelle Chew, MD, PhD, Associate professor. Department of Anaesthesiology Intensive care, Hallands Hospital Halmstad* Status NON-SEDA November 2014

Patients randomized N Kolding 51 Svendborg 12 Esbjerg 8 Århus 29 Tønsberg 5 Total 105 Patients randomized

100 200 300 400 500 600 700 01jan2014 0 NON-SEDA status November 2014 November NON-SEDA status Number included Number 01jan2015 Date 01jan2016 Number projected Number 31dec2016 I am not dead

I am only 24 waiting for NON-SEDA

17-11-2014