Clinical trial NCT03032471: Swiss SOS MoCA - DCI Study
Official title: Impact of Delayed Cerebral Ischemia (DCI) on the Neuropsychological Outcome After Aneurysmal Subarachnoid Hemorrhage - a SWISS SOS Multicentre Observational Study
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Subarachnoid Hemorrhage
Delayed Cerebral Ischemia
Stroke
Complication
Cognitive Impairment
Cognitive Deficit
Cognitive Deterioration
Cognitive Deficits Following Cerebral Infarction
Keywords: Subarachnoid Hemorrhage
Delayed cerebral ischemia
Cognitive Impairment
Montreal Cognitive Assessment
MoCA
Cognitive Deterioration
Lead sponsor: Swiss SOS Study Group
Sponsor class: OTHER
Collaborators: name: Insel Gruppe AG, University Hospital Bern
name: Département des Neurosciences cliniques, Service de Neurochirurgie, Hôpitaux Universitaires de Genève
name: Primario Neurochirurgia, EOC Ospedale Regionale di Lugano - Civico e Italiano
name: Klinik für Neurochirurgie, Kantonsspital St. Gallen
name: Klinik für Neurochirurgie, Universitätsspital Zürich
name: Primario Neurologia, EOC Ospedale Regionale di Lugano - Civico e Italiano
name: Abteilung für Neuropsychologie, Klinik für Neurologie, Kantonsspital St.Gallen
name: Abteilung für Neuropsychologie, Klinik für Neurologie, Universitätsspital Zürich
name: Département des Neurosciences cliniques, Service de Neurochirurgie, CHUV, Lausanne
name: Département des Neurosciences cliniques, Service de Neurologie, CHUV, Lausanne
name: Département des Neurosciences cliniques, Service de Neurologie, Hôpitaux Universitaires de Genève
First posted: 2017-01-26
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For part 1 of the study, patients with aneurysmal subarachnoid hemorrhage are recruited.

For part 2 of the study, patients with acute brain injury are recruited.

Brief summary: The primary objective of this multicenter observational study is to determine the effect size of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months after aSAH.

Secondary objectives are the feasibility to administer and the validity of the MoCA in an intensive care unit setting, as well as the test/retest reliability of the MoCA in patients with acute brain damage in absence of aSAH.

Detailed description: Background and rationale:

Delayed cerebral ischemia (DCI) is the independent most important predictor of neurological disability in survivors following aneurysmal subarachnoid hemorrhage (aSAH). DCI could also be identified as the most important predictor of moderate to severe neuropsychological impairment following aSAH. Only few prospective studies so far specifically analyzed the effect size of the relationship between DCI and neuropsychological impairment, and all studies had a methodological weakness: lack of a baseline neuropsychological assessment before the onset of DCI.

In studies analyzing the neuropsychological outcome after aSAH, the Montreal Cognitive Assessment (MoCA) is the most comprehensive, sensitive and specific instrument among the short tests. The MoCA is increasingly used in the aSAH population, while its validity and reliability has only been demonstrated in the normal population or patients suffering from diseases different from aSAH, such as e.g. Parkinson's disease or dementia. Today, neuropsychological examinations find entry into clinical routine for aSAH patients to estimate the need for inpatient rehabilitation. However, the MoCA is often applied to aSAH patients in a busy intensive or intermediate care unit, while it remains largely unknown whether the distraction in such an environment represents a bias to the obtained results.

This study therefore evaluates aSAH patients before and after the phase of DCI, as well as three months after aSAH, in order to estimate the impact of DCI on neuropsychological impairment. In addition, the extent and location of cerebral ischemia, as measured with the Alberta Stroke Program Early CT Score (ASPECTS) is correlated with the neuropsychological outcome.

Furthermore, the study measures the test/retest reliability of the MoCA, as well as the influence of the intensive care environment on the MoCA results in a randomized fashion in subjects with acute brain damage (and no aSAH).

Objectives:

The primary objective of this multicenter observational study is to determine the effect size of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months after aSAH.

Secondary objectives are the feasibility to administer and the validity of the MoCA in an intensive care unit setting, as well as the test/retest reliability of the MoCA in patients with acute brain damage in absence of aSAH.

Outcomes:

The primary endpoint is the proportion of patients with or without DCI that show worsening on the MoCA 3 months after the ictus as compared to before the DCI phase by at least two points.

Key secondary endpoints for part 1 of the study are:

* The proportion of patients with or without DCI that show worsening on the MoCA 14-28 days after the ictus as compared to before the DCI phase by at least two points.
* The absolute difference of the MoCA before and after the active phase of DCI in patients with versus without DCI.
* The absolute difference of the MoCA before the active phase of DCI and 3 months after aSAH in patients with versus without DCI
* The rate of patients with versus without DCI that show cognitive impairment at 14-28 days and 3 months (defined as MoCA \< 26 points)
* The correlation of neuropsychological outcome with the extent and location of ischemic lesions on brain CT-scan 12-21 days post-SAH, graded by the semi-quantitative ASPECT-grading
* Health-related quality of life at 3 months in patients with versus without DCI
* Home-time at 3 months in patients with versus without DCI
* Death and dependency at 3 months in patients with versus without DCI
* The absolute MoCA result, health-related quality of life and home-time at 3 months in patients with versus without hydrocephalus requiring shunting
* The absolute MoCA result, health-related quality of life and home-time at 3 months in patients with surgical versus endovascular aneurysm occlusion

Key secondary endpoints for part 2 of the study are:

* The test/retest reliability of the MoCA in patients with acute brain damage
* The influence of the intensive care environment on the MoCA in patients with acute brain damage

Eligibility criteria: Inclusion Criteria:

For part 1 of the study:

Participants fulfilling all of the following inclusion criteria are eligible for the study:

* Consent of the patient or consent of patient's next of kin (plus consent of an independent physician if patient is unable to consent)
* Aneurysmal SAH
* Age: ≥18
* Time of aSAH known (IMPORTANT: at least approximated. Time of aSAH refers to the bleed that lead to hospital admission; warning leaks in the patient history are not considered aSAH in this context)
* Complete aneurysm occlusion therapy within 48h after aSAH
* Glasgow coma scale (GCS) ≥ 13 points at time point 48h - 72h after aSAH
* Fluent language skills in either English, German, French, or Italian

For part 2 of the study:

Participants fulfilling all of the following inclusion criteria are eligible for the study:

* Consent of the patient or consent of patient's next of kin (plus consent of an independent physician if patient is unable to consent)
* Age: ≥18
* Acute brain injury that requires a in-patient treatment, e.g. for (surgical) treatment of a brain tumor, a cerebral hemorrhage, a hydrocephalus, stroke, or traumatic brain injury, with stable neurological and general health status
* Glasgow coma scale (GCS) ≥ 13 points
* Fluent language skills in either English, German, French, or Italian

Exclusion Criteria:

For part 1 of the study:

The presence of any one of the following exclusion criteria will lead to exclusion of the participant:

* SAH due to any other cause than aneurysm or structural abnormality of the brain (arterio-venous malformation, dural arterio-venous fistula, cavernous malformation, dissection, tumor, trauma)
* Comatose patients or patients with a reduced vigilance of GCS \< 13 at time point 48h - 72h after aSAH
* No aneurysm occlusion therapy within 48h after aSAH
* Clear signs of arterial vasospasm in the initial (CT-)angiography; indicating that aSAH had occurred already several days prior to admission
* Neurologic or psychiatric diseases other than aSAH that can potentially influence the test-performance of a patient on the MoCA (e.g., dementia, multiple sclerosis, bipolar disorder)
* Foreseeable difficulties in follow-up due to geographic reasons (e.g., patients living abroad)
* Patients who are not fluent in English, German, French, or Italian
* Patients requiring sedative or other medication that would interfere with the neuropsychological evaluation

For part 2 of the study:

The presence of any one of the following exclusion criteria will lead to exclusion of the participant:

* Instable neurological or general health-status of the patient, that makes a transport of the patient on the ICU or the office for neuropsychological testing impossible
* Suspected fluctuation of the neurological condition and the vigilance of the patient between first and second testing
* Known psychiatric disease that can potentially influence the test-performance on the MoCA (e.g., dementia, bipolar disorder)
* Patients who are not fluent in English, German, French, or Italian
* Patients requiring sedative or other medication that would interfere with the neuropsychological evaluation

Primary outcomes:
measure: Neuropsychological deterioration on the MoCA
timeFrame: 3 months after Subarachnoid Hemorrhage
Secondary outcomes:
measure: Neuropsychological deterioration on the MoCA
timeFrame: Up to 28 days after Subarachnoid Hemorrhage (directly after the DCI phase)
measure: Neuropsychological outcome
timeFrame: Up to 3 months after Subarachnoid Hemorrhage
measure: Reliability of the MoCA in patients with acute brain injury
timeFrame: Up to 1 month following acute brain injury
measure: Test-retest reliability of the MoCA in patients with acute brain injury
timeFrame: Up to 1 month following acute brain injury
measure: Correlation between MoCA and CT-imaging
timeFrame: Up to 72 hours after Subarachnoid Hemorrhage
measure: Correlation between MoCA and CT-imaging
timeFrame: Up to 28 days after Subarachnoid Hemorrhage (directly after the DCI phase)
measure: Correlation between MoCA and CT-imaging
timeFrame: 3 months after Subarachnoid Hemorrhage
measure: Dependency/Mortality
timeFrame: 3 months after Subarachnoid Hemorrhage
measure: Health-related quality of life (HRQoL)
timeFrame: 3 months after Subarachnoid Hemorrhage
measure: Shunt dependency (ventriculo-peritoneal or ventriculo-atrial shunt)
timeFrame: 3 months after Subarachnoid Hemorrhage
measure: Home time
timeFrame: 3 months after Subarachnoid Hemorrhage
measure: Minimum Clinically Important Difference (MCID) of the MoCA
timeFrame: Up to 3 months after Subarachnoid Hemorrhage
Other outcomes:
measure: Random number generation
timeFrame: Up to 1 month following acute brain injury
measure: Outcomes in patients with hydrocephalus vs. without hydrocephalus
timeFrame: Up to 3 months after Subarachnoid Hemorrhage
measure: Outcomes in patiens treated surgically vs. endovascularly (aneurysm occlusion)
timeFrame: Up to 3 months after Subarachnoid Hemorrhage
Locations:
city: Lugano
country: Switzerland
facility: Primario Neurochirurgia, EOC Ospedale Regionale di Lugano - Civico e Italiano
state: Ticino
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
city: Bern
country: Switzerland
facility: Universitätsklinik für Neurochirurgie, Inselspital Bern
city: Genève
country: Switzerland
facility: Département des Neurosciences cliniques, Service de Neurochirurgie, Hôpitaux Universitaires de Genève
city: St.Gallen
country: Switzerland
facility: Klinik für Neurochirurgie, Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: Klinik für Neurochirurgie, Universitätsspital Zürich
Study officials:
References:
citation: Stienen MN, Germans MR, Zindel-Geisseler O, Dannecker N, Rothacher Y, Schlosser L, Velz J, Sebok M, Eggenberger N, May A, Haemmerli J, Bijlenga P, Schaller K, Guerra-Lopez U, Maduri R, Beaud V, Al-Taha K, Daniel RT, Chiappini A, Rossi S, Robert T, Bonasia S, Goldberg J, Fung C, Bervini D, Maradan-Gachet ME, Gutbrod K, Maldaner N, Neidert MC, Fruh S, Schwind M, Bozinov O, Brugger P, Keller E, Marr A, Roux S, Regli L; MoCA-DCI Study Group; MoCA-DCI Study Group Contributors. Longitudinal neuropsychological assessment after aneurysmal subarachnoid hemorrhage and its relationship with delayed cerebral ischemia: a prospective Swiss multicenter study. J Neurosurg. 2022 Apr 29;137(6):1742-1750. doi: 10.3171/2022.2.JNS212595. Print 2022 Dec 1.