Is adding Cilostazol to nimodipine improving neurological outcome of patients with Aneurysmal Subarachnoid Hemorrhage? A randomized, double blind, placebo-controlled trial. CASH

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Apr 2026 → ongoing

Decision date (initial)

2025-05-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Our main objective is to show that 100mg twice a day of cilostazol over 14 days improves the modified Rankin scale at 6-months in aneurysmal SAH treated with nimodipine, against placebo

Secondary objectives 5

1. Secondary objectives are the functional status assessed at 6 months: -SubArachnoid Hemorrhage Outcome Tool (SAHOT) Score (Appendix 2) -MOCA score (Appendix 3) -Return to work -Activities of Daily Living (Appendix 4) -Instrumental Activities of Daily Living (Appendix 5)
2. And In-hospital morbi-mortality: -Length of ICU stay -Length of hospital stay -28-day mortality
3. Delayed cerebral ischemia, defined as the occurrence of focal neurological impairment or a decrease of at least 2 points on the Glasgow Coma Scale, which does not occur immediately after aneurysm occlusion and which is not ascribable to other causes.
4. Cerebral artery vasospasm, defined as a reduction of the diameter of the proximal cerebral vessels seen on either CT-, MR- or catheter angiography
5. Cerebral infarcts, detected on the CT scan or MRI performed with 6 weeks, (or on the latest CT scan or MRI performed before death within 6 weeks, or at autopsy), but not present on the earlier CT or MRI scan performed between 24 and 48 h after early aneurysm occlusion and not ascribable to other causes

Conditions and MedDRA coding

Aneurysmal Subarachnoid Hemorrhage

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adult patients admitted to an ICU with SAH related to a ruptured cerebral aneurysm occurring within the last 96 hours.
2. Aneurysm successfully secured by surgical clipping or endovascular coiling
3. Consent of the patient or, if not possible, from a proxy (emergency clause).
4. Registration in a national health care system

Exclusion criteria 8

1. Precritical modified Rankin Scale (mRS) > 2
2. Non-aneurysmal SAH
3. Delayed > 96h admission after first symptoms of SAH
4. Untreatable severe SAH with Hunt and Hess grade of V - Known allergy to cilostazol
5. Pregnancy
6. Pre-existing major hepatic, renal, pulmonary or cardiac disease
7. Concomitant use of one other anti-platelet and/or anticoagulant agent
8. Tutelage or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Modified Rankin Scale (mRS) assessed at 6 months in a structured face-to-face interview. Favorable outcome is defined by an mRS score 0 to 2, and unfavorable outcome by a mRS from 3 to 6. (Appendix 1)

Secondary endpoints 10

1. The main pitfall of the modified Rankin Scale is the overrating of patients that develop cognitive impairment. We thus chose to assess separately cognitive impairment with using specific scales, including the MOCA, ADL and IADL. The SAHOT (SAH-outcome tool) will be finally assessed, as it has been recently developed and validated but not yet commonly used as the mRS (18).
2. Other generic morbidity criterion will be used: Length of Intensive Care Unit (ICU) stay. Length of hospital stay. 28-day mortality
3. Delayed cerebral ischemia, defined by the appearance of a focal neurological deficit or a decrease of at least 2 points on the Glasgow Coma Scale, which is not apparent immediately after surgical or endovascular treatment of the aneurysm and not attributable to other causes.
4. Short-term course of angiographically defined vasospasm, defined as a reduction in the caliber of proximal cerebral vessels observed by CT, MRI, or catheter angiography
5. Cerebral infarctions, defined by a diagnosis of cerebral infarction made by CT scan or MRI within 6 weeks, or on the last CT scan or MRI performed before death within 6 weeks, or at autopsy, not present on the CT scan or MRI between 24 and 48 hours after early aneurysm occlusion
6. Occurrence of DCI during the ICU stay
7. Occurrence of cerebral vasospasm on a brain imaging on digitally substracted angiography (DSA) or Magnetic resonance/computed tomography angiogram (MR/CTA) performed upon clinical signs of delayed cerebral ischemia or severe impairment of cerebral blood velocity in transcranial doppler
8. Occurrence of new cerebral infarcts
9. Occurrence of cilostazol-related major adverse events, including: arrythmia, abnormal bleeding and allergy.
10. Occurrence of cilostazol-related minor adverse events include: tachycardia, fever, fainting, nausea, vomiting and stomach pain.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Sponsor organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Address

1 Rue Cabanis

City

Paris

Postcode

75014

Country

France

Scientific contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

SYLLA

Public contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

SYLLA

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications