UMIN-CTR Clinical Trial

Public title

Prospective registry for searching mediators of neurovascular events after aneurysmal subarachnoid hemorrhage

Acronym

pSEED

Scientific Title

Prospective registry for searching mediators of neurovascular events after aneurysmal subarachnoid hemorrhage

Scientific Title:Acronym

pSEED

Region

Japan

Condition

aneurysmal subarachnoid hemorrhage

Classification by specialty

Neurosurgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate if blood levels of matricellular proteins are useful for early diagnosis or prediction of neurovascular events such as early brain injury, cerebral vasospasm, delayed cerebral ischemia, and hydrocephalus after subarachnoid hemorrhage

Basic objectives2

Others

Basic objectives -Others

To investigate if blood levels of matricellular proteins predict outcomes after subarachnoid hemorrhage.

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

3-month outcome
Delayed cerebral infarction

Key secondary outcomes

Matricellular protein levels in blood at days 1-3, 4-6, 7-9, and 10-12
Early brain injury
Cerebral vasospasm
Delayed cerebral ischemia
Chronic hydrocephalus

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Written informed consent
2. More than 20 years of age at onset
3. modified Rankin Scale 0-2 before onset
4. Subarachnoid hemorrhage (SAH) on computed tomography (CT) scans or lumbar puncture
5. Saccular aneurysm as the cause of SAH confirmed on digital subtraction angiography or CT angiography
6. Aneurysmal obliteration by clipping or coiling within 48 hours of onset

Key exclusion criteria

1. Non-idiopathic saccular aneurysms including traumatic, dissecting, tumor-related, and inflammatory aneurysms
2. Aneurysm treatment by parent artery occlusion
3. Patients with procedure-related complications
4. Severe systemic complications limiting routine post-operative managements
5. Diseases that potentially affect matricellular protein levels
6. Patients who are judged as being inappropriate by attending neurosurgeons

Target sample size

500

Name of lead principal investigator

1st name	Hidenori
Middle name
Last name	Suzuki

Organization

Mie University

Division name

Graduate School of Medicine, Department of Neurosurgery

Zip code

514-8507

Address

2-174 Edobashi, Tsu, Mie 514-8507, Japan

TEL

059-231-5503

Email

suzuki02@clin.medic.mie-u.ac.jp

Name of contact person

1st name	Hidenori
Middle name
Last name	Suzuki

Organization

Mie University

Division name

Graduate School of Medicine, Department of Neurosurgery

Zip code

514-8507

Address

2-174 Edobashi, Tsu, Mie 514-8507, Japan

TEL

059-231-5503

Homepage URL

Email

suzuki02@clin.medic.mie-u.ac.jp

Institute

Mie University Graduate School of Medicine,
Department of Neurosurgery

Institute

Department

Personal name

Organization

Mie University Graduate School of Medicine,
Department of Neurosurgery

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

The ethical committee of Mie University Hospital

Address

2-174 Edobashi, Tsu, Mie 514-8507, Japan

Tel

059-231-5246

Email

s-kenkyu@mo.medic.mie-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

07

Month

07

Day

URL releasing protocol

https://doi.org/10.1016/j.hest.2024.02.001

Publication of results

Partially published

URL related to results and publications

https://doi.org/10.1016/j.clineuro.2024.108634

Number of participants that the trial has enrolled

305

Results

A total of 229 aneurysmal subarachnoid hemorrhage (aSAH) patients were analyzed, and chronic hydrocephalus (CH) occurred in 67 patients. Multivariate logistic regression analyses using clinical variables related to CH on univariate analyses and plasma fibulin-5 (FBLN5) levels at days 4-6 post-aSAH revealed that more than 366.4 ng/mL of FBLN5 levels at days 4-6 post-aSAH (adjusted odds ratio, 3.14) were an independent determinant of subsequent CH development.

Results date posted

2025

Year

07

Month

13

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The inclusion criteria were as follows: more than 20 years of age at onset, pre-onset modified Rankin scale 0-2, subarachnoid hemorrhage (SAH) diagnosed using computed tomography (CT) scans, saccular aneurysm as the cause of SAH confirmed on CT angiography or digital subtraction angiography, and aneurysmal obliteration via surgical clipping or endovascular coiling. The following patients were excluded, following the recommendations of previous studies, because their pathology is different from SAH caused by a ruptured saccular aneurysm: patients with dissecting, traumatic, mycotic, and arteriovenous malformation-related aneurysms or SAH of unknown etiology. After angiographic confirmation of a ruptured intracranial aneurysm, surgical clipping or endovascular coiling of the lesion was performed as judged by the attending neurosurgeon to be appropriate for the individual patient.

Participant flow

The present study investigated the data of consecutive patients registered to the Prospective Registry for Searching Mediators of Neurovascular Events after Aneurysmal Subarachnoid Hemorrhage (aSAH) (pSEED), which was conducted in nine tertiary referral centers in Mie prefecture in Japan from September 2013 to December 2016. In the registry, clinical variables were recorded, and plasma samples were serially collected at days 1-3, 4-6, 7-9, and 10-12 after onset of aSAH. The exclusion criteria were (1) past history of chronic hydrocephalus (CH); (2) missing data of clinical variables; (3) no stocked plasma samples; (4) aneurysmal treatments other than clipping or coiling, that is, parent artery occlusion with or without bypass surgery, aneurysmal wrapping or coating, and use of off-label devices in Japan such as stents; and (5) coexistence of inflammatory diseases that may upregulate fibulin-5 (FBLN5). Plasma FBLN5 levels were measured with stocked samples, and clinical variables were retrospectively analyzed.

Adverse events

None.

Outcome measures

Delayed cerebral ischemia, delayed cerebral infarction, angiographic vasospasm, chronic hydrocephalus, and modified Rankin scale at discharge and 3 monnths after subarachnoid hemorrhage onset

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2013

Year

05

Month

14

Day

Date of IRB

2013

Year

05

Month

14

Day

Anticipated trial start date

2013

Year

05

Month

14

Day

Last follow-up date

2023

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This is an observational study to investigate the relationships between blood levels of various matricellular proteins at days 1-3, 4-6, 7-9, and/or 10-12, and neurovascular events and/or 3-month outcome after aneurysmal subarachnoid hemorrhage.

Registered date

2018

Year

07

Month

07

Day

Last modified on

2025

Year

07

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037982