Sedation of Cerebrovascular Ventilated Critical Care PatientsPhase 2MODERNISENCT02317497

Sedation Depth in Neurocritical Care

A Phase 2 study testing Intensive Care Sedation (depth, level), Vasopressors to maintain normal blood pressure values, if needed and Osmotherapeutics to lowr intracranial pressure, if needed in people with Sedation of Cerebrovascular Ventilated Critical Care Patients, run by Heidelberg University at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Sedation of Cerebrovascular Ventilated Critical Care Patients
What is being tested?: Intensive Care Sedation (depth, level), Vasopressors to maintain normal blood pressure values, if needed and Osmotherapeutics to lowr intracranial pressure, if needed
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 100 participants
Where: 1 siteGermany
Study dates: Sep 2016to Nov 2018
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

age 18 years or older, either sex,
one of the following confirmed admission diagnoses:
non-traumatic acute ischemic infarction (AIS)
non-traumatic intracerebral hemorrhage (ICH)
non-traumatic subarachnoid hemorrhage (SAH),
ventilated with expected need of further artificial ventilation for more than 72h,
expected ICU-LOS of more than 5 days,
informed consent by a legal representative.

Who cannot join

pregnancy
intubation and artificial ventilation for less than 3 days
severe adult respiratory distress Syndrome (ARDS)
severe sepsis
other systemic disorders that demand deep sedation
extreme agitation

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need of pharmacological paralysis
epileptic state
refractory intracranial hypertension
participation in any other interventional trial
life expectancy < 3 weeks, very poor prognosis

Trial locations and contacts

1 site in 1 country.

Julian Bösel, MD contact

+49 6221 5639145

julian.boesel@med.uni-heidelberg.de

Germany1 site

NeuroIntensive Care Unit, Department of Neurology, University Hospital Heidelberg
Heidelberg, D-69120

Other trials in Germany

About this study

Official title: MOderate vs DEep Regimen in NeuroIntensive Care SEdation

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.

Read the 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.

Conditions: Sedation of Cerebrovascular Ventilated Critical Care Patients
Being tested: Intensive Care Sedation (depth, level), Vasopressors to maintain normal blood pressure values, if needed, Osmotherapeutics to lowr intracranial pressure, if needed, Endovascular stroke care to treat brain vessel occlusions, if needed, Decompressive neurosurgery, if needed
Keywords: Neurocritical care, Severe Stroke, Ischemic stroke, Intracerebral hemorrhage, Subarachnoid hemorrhage, Sedation, RASS, BIS
Medical subject headings: Stroke, Ischemic Stroke, Cerebral Hemorrhage, Subarachnoid Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intensive Care Sedation (depth, level)Other
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.
Vasopressors to maintain normal blood pressure values, if neededDrug
Osmotherapeutics to lowr intracranial pressure, if neededDrug
Endovascular stroke care to treat brain vessel occlusions, if neededProcedure or surgery
Decompressive neurosurgery, if neededProcedure or surgery

Study groups in NCT02317497
Study group	Role	What they receive
Moderate sedation (M)	Experimental	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. Receives: 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
Deep sedation (D)	Active comparator	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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

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]
Measured: Admission to Discharge, ca. 3 weeks from onset

Secondary outcomes (17)

In-hospital stay
[days from admission until discharge from hospital]
Measured: 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]
Measured: 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]
Measured: within hospital stay, ca. 3 weeks from onset
Sedation duration
[Sum of half-days on any sedative medication (irrespective of analgesic drugs)]
Measured: within hospital stay, ca. 3 weeks from onset
Opioid Analgesia duration
[Sum of half-days on any opioid medication (irrespective of sedative drugs)]
Measured: 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]
Measured: 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
Measured: 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]
Measured: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Vasopressor Dependence
[Sum of half-days spent under any vasopressors]
Measured: 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]
Measured: 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]
Measured: 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]
Measured: 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]
Measured: within hospital stay, ca. 3 weeks from onset
Complications [number and type of pre-defined complications ]
[number and type of pre-defined complications ]
Measured: within hospital stay, ca. 3 weeks from onset
Functional Outcome [modified Rankin Scale (mRS)
[modified Rankin Scale (mRS) at 3 months from insult]
Measured: 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]
Measured: 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]
Measured: within hospital stay, ca. 3 weeks from onset

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2016Nov 2018

First posted16 Dec 2014 (estimated)
Study startSep 2016
Primary completionJan 2018 (estimated)
Study completionNov 2018 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Sedation of Cerebrovascular Ventilated Critical Care PatientsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 100 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02317497
Sponsor's protocol ID: MODERNISE_Prot_HD
Acronym: MODERNISE
Status last verified: Jun 2016
First submitted: 19 Nov 2014
Last updated: 21 Jun 2016
Results posted: No
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 21 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: MOderate vs DEep Regimen in NeuroIntensive Care SEdation
ClinicalTrials.gov ID: NCT02317497
Acronym / sponsor ID: MODERNISE / MODERNISE_Prot_HD
Conditions: Sedation of Cerebrovascular Ventilated Critical Care Patients
Keywords: Neurocritical care, Severe Stroke, Ischemic stroke, Intracerebral hemorrhage, Subarachnoid hemorrhage, Sedation, RASS, BIS
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 100 participants (estimated)
Lead sponsor: Heidelberg UniversityUniversity, hospital or other
Study start: Sep 2016
Primary completion: Jan 2018 (estimated)
Study completion: Nov 2018 (estimated)
First posted: 16 Dec 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Moderate sedation (M)	Experimental	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 needed1. 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.
Deep sedation (D)	Active comparator	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 needed2. 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

age 18 years or older, either sex,
one of the following confirmed admission diagnoses:
ventilated with expected need of further artificial ventilation for more than 72h,
expected ICU-LOS of more than 5 days,
informed consent by a legal representative.

Key exclusion criteria (11 listed)

pregnancy
intubation and artificial ventilation for less than 3 days
severe adult respiratory distress Syndrome (ARDS)
severe sepsis
other systemic disorders that demand deep sedation

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intensive Care Sedation (depth, level)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.	Other	Deep sedation (D), Moderate sedation (M)
Vasopressors to maintain normal blood pressure values, if needed	Drug	Deep sedation (D), Moderate sedation (M)
Osmotherapeutics to lowr intracranial pressure, if needed	Drug	Deep sedation (D), Moderate sedation (M)
Endovascular stroke care to treat brain vessel occlusions, if needed	Procedure or surgery	Deep sedation (D), Moderate sedation (M)
Decompressive neurosurgery, if needed	Procedure or surgery	Deep sedation (D), Moderate sedation (M)

Primary outcome

Intensive Care Unit Length of Stay (ICU-LOS)
Time frame: Admission to Discharge, ca. 3 weeks from onset
• Intensive care unit length of stay (ICU-LOS) [days from admission until discharge from the intensive care unit]

17 secondary outcomes

In-hospital stay
Time frame: within hospital stay, ca. 3 weeks from onset
Ventilation-free ICU-LOS
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Ventilation
Time frame: within hospital stay, ca. 3 weeks from onset
Sedation duration
Time frame: within hospital stay, ca. 3 weeks from onset
Opioid Analgesia duration
Time frame: within hospital stay, ca. 3 weeks from onset
Time within sedation goal
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Ventilator Weaning
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Analgesia and Sedation Dependence
Time frame: within hospital stay, ca. 3 weeks from onset
Accumulated Duration of Vasopressor Dependence
Time frame: within hospital stay, ca. 3 weeks from onset
Average ICP during sedation target period (if available)
Time frame: within hospital stay, ca. 3 weeks from onset
Average BIS during sedation target period
Time frame: within hospital stay, ca. 3 weeks from onset
Average BIS after sedation target period
Time frame: within hospital stay, ca. 3 weeks from onset
Occurrence and Duration of Sepsis
Time frame: within hospital stay, ca. 3 weeks from onset
Complications [number and type of pre-defined complications ]
Time frame: within hospital stay, ca. 3 weeks from onset
Functional Outcome [modified Rankin Scale (mRS)
Time frame: 3 months from insult
Mortality
Time frame: during the ICU-stay or in-hospital stay or within 3 months after admission
Cost of Treatment
Time frame: within hospital stay, ca. 3 weeks from onset

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2016.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Julian Bösel, MD contact

+49 6221 5639145

julian.boesel@med.uni-heidelberg.de

Julian Bösel, MD principal investigator

Dep. of Neurology, University of Heidelberg, Germany

Alejandro Rabinstein, MD principal investigator

Dep. of Neurology, Mayo Clinic, Rochester, USA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Julian Bösel, MD (+49 6221 5639145, julian.boesel@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intensive Care Unit Length of Stay (ICU-LOS) (time frame: Admission to Discharge, ca. 3 weeks from onset). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02317497.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2016.