Clinical trial NCT02317497: Sedation Depth in Neurocritical Care
Official title: MOderate vs DEep Regimen in NeuroIntensive Care SEdation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Sedation of Cerebrovascular Ventilated Critical Care Patients
Keywords: Neurocritical care
Severe Stroke
Ischemic stroke
Intracerebral hemorrhage
Subarachnoid hemorrhage
Sedation
RASS
BIS
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2014-12-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Background: Sedation of the intensive care unit (ICU) patient is necessary to relieve the patient from pain, anxiety and agitation and to enable mechanical ventilation, diagnostic investigations and invasive procedures. While sedation policy has shifted from deep sedation to moderate, minimal, or even no sedation in the general ICU, optimal sedation of the cerebrovascular ICU patient is unclear and controversial.

Method: MOderate vs DEep Regime in NeuroIntensive care SEdation (MODERNISE) is a prospective, randomized, open, two-center trial. Patients with acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage who need to be ventilated are eligible for enrollment. It is intended to enroll 50 patients per group (n=100). Patients are randomized within 72h from admission to either moderate sedation as defined by Richmond Agitation Sedation Scale (RASS) \>= -3 or to deep sedation as defined by RASS \< -3 for the next 72h, after which weaning from sedation is aimed for in a stepwise fashion in both groups. If reduction of sedation is not feasible, patients remain at their respective sedation level for another 12 hours, and sedation reduction is then tried again. Patients are multimodally monitored for systemic and cerebral parameters (the latter including bispectral index (BIS) monitoring). The primary endpoint is ICU length of stay (ICU-LOS); secondary endpoints are several pre-defined variables of the ICU course, feasibility of sedation levels without violation of pre-defined safety criteria, pre-defined complications, and short- and long-term functional outcome and mortality.

Conclusion: The feasibility, safety and benefits of moderate as opposed to deep sedation even in the acute phase of severe cerebrovascular disease needs to be clarified in a prospective randomized study. Results from this study might change sedation regimes and help prevent unwanted effects of deep sedation in the brain-injured patient.

Detailed description: Executive Summary Rationale While sedation policy has shifted from deep sedation to moderate, minimal, or even no sedation in the general ICU, optimal sedation of the cerebrovascular neuro-ICU (NICU) patient is unclear and controversial. The rationale of this study is to analyze potential benefits, feasibility and safety of moderate as opposed to deep sedation.

Aim and hypothesis MODERNISE is a pilot trial aiming to investigate the safety, feasibility and potential benefits of moderate vs. deep sedation in patients with severe ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. The primary objective is to compare moderate sedation and deep sedation with respect to ICU-LOS.

Design MODERNISE is a prospective, randomized, controlled, outcome observer-blinded, two-center trial. Patients are randomized to either moderate sedation as defined by RASS) \>= -3 or to deep sedation as defined by RASS \< -3.

Study Outcomes The primary endpoint is ICU-LOS. Secondary endpoints are the ventilation-free ICU-LOS, ventilation duration, sedation duration, complications (including episodes of treatment-demanding increases of intracranial pressure (ICP), episodes of hypotension, episodes of cerebral hypoperfusion, pneumonia, sepsis, ileus, episodes of paroxysmal sympathetic hyperactivity (PSH)), time within sedation goal, demand of sedatives, demand of analgesics, demand of vasopressors, scores (RASS, nociception coma scale (NCS), Glasgow Coma Scale (GCS), intensive care delirium screening checklist (ICDSC), confusion assessment method - ICU (CAM-ICU), ICU mortality, in-hospital mortality, modified Rankin Scale (mRS) at 90 days, PTSD at 90 days.

Discussion To clarify the benefits of moderate sedation in critical care ventilated stroke patients, a randomized multicentre trial is clearly needed. If this two-center pilot trial shows differences in relevant parameters of the ICU course and gives promising safety and feasibility results, a multi-centre trial may be planned on this basis.

Eligibility criteria: Inclusion Criteria:

1. age 18 years or older, either sex,
2. one of the following confirmed admission diagnoses:

   * non-traumatic acute ischemic infarction (AIS)
   * non-traumatic intracerebral hemorrhage (ICH)
   * non-traumatic subarachnoid hemorrhage (SAH),
3. ventilated with expected need of further artificial ventilation for more than 72h,
4. expected ICU-LOS of more than 5 days,
5. informed consent by a legal representative.

Exclusion Criteria:

1. pregnancy
2. intubation and artificial ventilation for less than 3 days
3. severe adult respiratory distress Syndrome (ARDS)
4. severe sepsis
5. other systemic disorders that demand deep sedation
6. extreme agitation
7. need of pharmacological paralysis
8. epileptic state
9. refractory intracranial hypertension
10. participation in any other interventional trial
11. life expectancy \< 3 weeks, very poor prognosis

Primary outcomes:
measure: Intensive Care Unit Length of Stay (ICU-LOS)
timeFrame: Admission to Discharge, ca. 3 weeks from onset
Secondary outcomes:
measure: In-hospital stay
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Ventilation-free ICU-LOS
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Accumulated Duration of Ventilation
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Sedation duration
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Opioid Analgesia duration
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Time within sedation goal
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Accumulated Duration of Ventilator Weaning
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Accumulated Duration of Analgesia and Sedation Dependence
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Accumulated Duration of Vasopressor Dependence
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Average ICP during sedation target period (if available)
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Average BIS during sedation target period
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Average BIS after sedation target period
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Occurrence and Duration of Sepsis
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Complications [number and type of pre-defined complications ]
timeFrame: within hospital stay, ca. 3 weeks from onset
measure: Functional Outcome [modified Rankin Scale (mRS)
timeFrame: 3 months from insult
measure: Mortality
timeFrame: during the ICU-stay or in-hospital stay or within 3 months after admission
measure: Cost of Treatment
timeFrame: within hospital stay, ca. 3 weeks from onset
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: NeuroIntensive Care Unit, Department of Neurology, University Hospital Heidelberg
Study officials:
affiliation: Dep. of Neurology, University of Heidelberg, Germany
name: Julian Bösel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Mayo Clinic, Rochester, USA
name: Alejandro Rabinstein, MD
role: PRINCIPAL_INVESTIGATOR
References: