Cilostazol With Nimodipine to Improve Outcome After Aneurysmal Subarachnoid Hemorrhage
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Cilostazol (Pletal®) 100 mg Tablets, Placebo, Nimodipine group.
- Who it may be relevant to
- Registry conditions: Aneurysmal Subarachnoid Hemorrhage. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Is Adding Cilostazol to Nimodipine Improving Neurological Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage? A Randomized, Double Blind, Placebo-controlled Trial
Overview
The CASH study is a randomized, double-blind, placebo-controlled trial evaluating whether adding cilostazol to standard nimodipine therapy improves neurological outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). The primary objective is to assess functional outcome at 6 months using the modified Rankin Scale. A total of 630 patients will be enrolled within 96 hours of aSAH onset and treated for 14 days. The study is conducted across 9 centers in France, funded by a PHRC, and overseen by an independent monitoring board.
Detailed description
The CASH trial (Cilostazol in Aneurysmal Subarachnoid Hemorrhage) is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial investigating whether the addition of cilostazol to standard nimodipine therapy improves long-term neurological outcomes in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH).
Secondary brain injury following aSAH, particularly delayed cerebral ischemia (DCI) and vasospasm, remains a major cause of mortality and long-term disability. Currently, nimodipine is the only drug with proven efficacy in improving neurological outcomes after aSAH. However, emerging data-mostly from studies conducted in Japan-suggest that cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor with antiplatelet and vasodilatory effects, may further reduce the risk of ischemic complications and disability when added to standard care.
The cilostazol mechanism includes inhibition of platelet aggregation via cAMP enhancement, vasodilation via nitric oxide release, and endothelial protection. Experimental studies also suggest neuroprotective effects such as attenuation of cortical spreading depolarizations and inhibition of vascular smooth muscle cell proliferation.
The trial will enroll 630 adult patients admitted to intensive care units within 96 hours of a confirmed aSAH due to a ruptured aneurysm that has been secured by either surgical clipping or endovascular coiling. Patients will be randomly assigned to receive either cilostazol 100 mg twice daily for 14 days (administered orally or via gastric tube) or placebo, alongside the standard 21-day nimodipine regimen.
The primary endpoint is the neurological outcome at 6 months, assessed by the modified Rankin Scale (mRS). Secondary outcomes include cognitive performance (MoCA score), return to work, independence in daily activities, hospital and ICU stay durations, 28-day mortality, and incidence of DCI, vasospasm, and cerebral infarctions as defined by imaging or clinical criteria.
The study will be conducted over 49 months (42 months of enrollment + 6 months of follow-up), across 9 French centers, with an expected inclusion rate of 1.9 patients per center per month. Two interim analyses are planned. The study is funded by a Programme Hospitalier de Recherche Clinique (PHRC) and monitored by an independent data safety monitoring board (DSMB).
While cilostazol is generally well tolerated, especially in short-term use, potential side effects include headache, palpitations, diarrhea, arrhythmias, bleeding, and allergic reactions. Previous short-term studies suggest an acceptable safety profile in aSAH patients.
If positive, the CASH study may significantly impact clinical guidelines by supporting the inclusion of cilostazol as an adjunct therapy in the management of aneurysmal subarachnoid hemorrhage.
Interventions
- Biological Cilostazol (Pletal®) 100 mg Tablets
100 mg orally or via feeding tube twice daily for 14 days, starting within 96 hours after aneurysmal subarachnoid hemorrhage onset. Tablets may be crushed for enteral administration. - Drug Placebo
Oral or enteral placebo, visually identical to cilostazol, twice daily for 14 days, starting within 96 hours after hemorrhage onset. - Drug Nimodipine group
Administered orally, enterally, or intravenously for 21 days as part of standard of care. Dose, route, and duration determined by treating physician according to clinical condition and guidelines.
Primary outcome measures
- Modified Rankin Scale (mRS) Score at 6 Months After Aneurysmal Subarachnoid Hemorrhage [Time frame: At 6 months after aneurysmal subarachnoid hemorrhage]
Secondary outcome measures (8)
- Functional Outcome at 6 Months Measured by the Subarachnoid Hemorrhage Outcome Tool (SAHOT) [Time frame: 6 months]
- In-hospital morbidity and mortality [Time frame: 28 days]
- Clinical and radiological events predictive of functional status [Time frame: 6 months]
- Incidence of Cilostazol-Related Major and Minor Adverse Events [Time frame: 6 months.]
- Cognitive Function at 6 Months Measured by the Montreal Cognitive Assessment (MoCA) [Time frame: 6 months]
- Return to Work at 6 Months [Time frame: 6 months]
- Activities of Daily Living (ADL) at 6 Months [Time frame: 6 months]
- Instrumental Activities of Daily Living (IADL) at 6 Months [Time frame: 6 months]
Eligibility criteria
Inclusion criteria
- Adult patients admitted to an ICU with SAH related to a ruptured cerebral aneurysm occurring within the last 96 hours.
- Aneurysm successfully secured by surgical clipping or endovascular coiling
- Consent of the patient or, if not possible, from a proxy (emergency clause).
- Registration in a national health care system
Exclusion criteria
- \- Precritical modified Rankin Scale (mRS) > 2
- Nonaneurysmal SAH
- Delayed >96h admission after first symptoms of SAH
- Coma defined by GCS of 3-5 with untreatable aneurysm will be excluded"
- Known allergy to cilostazol
- Pregnancy
- Pre-existing major hepatic, renal, pulmonary or cardiac disease
- Concomitant use of one other anti-platelet and/or anticoagulant agent
- SAH diagnosed on Lumbar puncture with no evidence of blood on CT.
- Tutelage or guardianship
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Triple blind
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07144956 · D24-009 · 2024-516468-27-00