A Phase 2 interventional study of Intensive Care Sedation (depth, level) and Vasopressors to maintain normal blood pressure values, if needed in Sedation of Cerebrovascular Ventilated Critical Care Patients, sponsored by Heidelberg University. Status unknown at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-06-21.
Sponsored by Heidelberg University · Phase 2, Interventional, and Supportive care
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.
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.
Heidelberg University is the lead sponsor of 279 studies on the registry; 17 are open to participants now.
Counted across the registry records on this site, refreshed daily.
one of the following confirmed admission diagnoses:
Exclusion Criteria:
1. Moderate sedation defined by target RASS of \>= -3. The intervention (M) is sedation by use of any sedative and/or analgesic medication(s) left at the discretion of the treating physicians targeted at a RASS of \>= -3 (patient responds to verbal stimulus) from randomization for the next 72h. RASS will be assessed once every 8 h (at he beginning of each shift) and measures undertaken to achieve the target level. If safety-limits are violated, sedation may have to be deepened below the target level for 8h and re-assessed at the beginning of the next shift with the aim to approach the target level of the intervention group again.
Other: Intensive Care Sedation (depth, level) · Drug: Vasopressors to maintain normal blood pressure values, if needed · Drug: Osmotherapeutics to lowr intracranial pressure, if needed · Procedure: Endovascular stroke care to treat brain vessel occlusions, if needed · Procedure: Decompressive neurosurgery, if needed
2. Deep sedation defined by target RASS of \< -3. The control (D) is sedation by use of any sedative and/or analgesic medication(s) left at the discretion of the treating physicians targeted at a RASS of \< -3 (patient does not respond to verbal stimulus) from randomization for the next 72h. RASS will be assessed once every 8 h (at he beginning of each shift) and measures undertaken to achieve the target level. If safety-limits are violated, sedation may have to be reduced above the target level for 8h and re-assessed at the beginning of the next shift with the aim to approach the target level of the control group again.
Other: Intensive Care Sedation (depth, level) · Drug: Vasopressors to maintain normal blood pressure values, if needed · Drug: Osmotherapeutics to lowr intracranial pressure, if needed · Procedure: Endovascular stroke care to treat brain vessel occlusions, if needed · Procedure: Decompressive neurosurgery, if needed
As far as sedation is concerned, this will be adapted to all patients before randomization in the first 3 days according to what the diagnosis and acute treatment of the underlying disease demands. This will be deep sedation or even general anesthesia (for operative procedures) in most cases. After 72h at the sedation level of the respective randomization result, both groups will tried to be weaned from sedation with the goal of awakening, weaning from ventilation, overall de-escalation and transfer to rehabilitation as far as the course of the disease and the occurrence of complications allows. This reduction of sedation will follow individual regimes at he discretion of the treating physician. However, if cessation of sedation violates safety-limits (see below, Tab. 2) or is not feasible for other reasons, return to the level the patient was initially randomized for (or even below that) is mandatory with a re-assessment of safety for sedation weaning after 12h aimed for.
Intensive Care Unit Length of Stay (ICU-LOS)
• Intensive care unit length of stay (ICU-LOS) \[days from admission until discharge from the intensive care unit\]
Time frame: Admission to Discharge, ca. 3 weeks from onset
In-hospital stay
\[days from admission until discharge from hospital\]
Time frame: within hospital stay, ca. 3 weeks from onset
Ventilation-free ICU-LOS
\[days from ventilator-independence for 24 h until discharge from the intensive care unit\]
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Ventilation
\[Sum of half-days on the ventilator until the patient is ventilator-independent for 24 h\]
Time frame: within hospital stay, ca. 3 weeks from onset
Sedation duration
\[Sum of half-days on any sedative medication (irrespective of analgesic drugs)\]
Time frame: within hospital stay, ca. 3 weeks from onset
Opioid Analgesia duration
\[Sum of half-days on any opioid medication (irrespective of sedative drugs)\]
Time frame: within hospital stay, ca. 3 weeks from onset
Time within sedation goal
\[Sum of 8h-shifts fulfilling the randomized sedation target during the 72h after randomization or above that target afterwards within the first NICU week\]
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Ventilator Weaning
\[Sum of half-days spent under the application of a ventilator weaning protocol
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Analgesia and Sedation Dependence
\[ Sum of half-days requiring the application of sedatives and analgesics\]
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Vasopressor Dependence
\[Sum of half-days spent under any vasopressors\]
Time frame: within hospital stay, ca. 3 weeks from onset
Average ICP during sedation target period (if available)
\[Median and interquartile range of 3 x 3 maximum ICP measurements per shift during the 72h after randomization\]
Time frame: within hospital stay, ca. 3 weeks from onset
Average BIS during sedation target period
\[Median and interquartile range of 3 x 3 x average BIS measurements per shift during the 72h from randomization\]
Time frame: within hospital stay, ca. 3 weeks from onset
Average BIS after sedation target period
\[Median and interquartile range of 3 x 3 x average BIS measurements per shift from 72h after randomization to discharge\]
Time frame: within hospital stay, ca. 3 weeks from onset
Occurrence and Duration of Sepsis
\[number of episodes and duration of sepsis as defined by international criteria\]
Time frame: within hospital stay, ca. 3 weeks from onset
Complications [number and type of pre-defined complications ]
\[number and type of pre-defined complications \]
Time frame: within hospital stay, ca. 3 weeks from onset
Functional Outcome [modified Rankin Scale (mRS)
\[modified Rankin Scale (mRS) at 3 months from insult\]
Time frame: 3 months from insult
Mortality
\[death of any cause and type of death during the ICU-stay or in-hospital stay or within 3 months after admission\]
Time frame: during the ICU-stay or in-hospital stay or within 3 months after admission
Cost of Treatment
\[total ICU-cost estimated by length of stay and severity-based disease-related Groups\] multiplicator of each individual patient\] \[total ICU-cost estimated by length of stay and severity-based DRG multiplicator of each individual patient\]
Time frame: within hospital stay, ca. 3 weeks from onset
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Heidelberg University