Cilostazol With Nimodipine to Improve Outcome After Aneurysmal Subarachnoid Hemorrhage

NCT07144956 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: D24-0092024-516468-27-00
• Study Type: interventional
• Target: 630
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

Cilostazol; Nimodipine; Vasospasm; Modified Rankin Scale (mRS); Neurological outcome; Double-blind; Randomized Controlled Trial; Multicenter clinical trial

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Scale (mRS) Score at 6 Months After Aneurysmal Subarachnoid Hemorrhage

  Neurological functional outcome will be measured using the modified Rankin Scale (mRS) at 6 months post-aneurysmal subarachnoid hemorrhage. The mRS is a 7-point ordinal scale ranging from 0 (no symptoms) to 6 (death), assessing the degree of disability or dependence in daily activities.

  At 6 months after aneurysmal subarachnoid hemorrhage

Secondary Outcomes (8)

• Functional Outcome at 6 Months Measured by the Subarachnoid Hemorrhage Outcome Tool (SAHOT)

  6 months

• In-hospital morbidity and mortality

  28 days

• Clinical and radiological events predictive of functional status

  6 months

• Incidence of Cilostazol-Related Major and Minor Adverse Events

  6 months.

• Cognitive Function at 6 Months Measured by the Montreal Cognitive Assessment (MoCA)

  6 months

Study Arms (2)

Cilostazol + Nimodipine

EXPERIMENTAL

In the cilostazol arm, patients will receive standard care for aneurysmal subarachnoid hemorrhage, including nimodipine administration as recommended by French and European guidelines for delayed cerebral ischemia (DCI) prevention. In addition, participants will receive cilostazol 100 mg twice daily, administered orally or via gastric tube if swallowing is not possible, for 14 consecutive days, starting within 96 hours of hemorrhage onset. Cilostazol tablets may be crushed for enteral administration. All other preventive and curative treatments for vasospasm or DCI-such as hypertensive therapy, milrinone, or endovascular interventions-are permitted at the discretion of the treating physician. Monitoring will include clinical status, occurrence of vasospasm, DCI, cerebral infarction, and cilostazol-related adverse events. Follow-up visits and safety assessments will be identical to the placebo arm.

Biological: Cilostazol (Pletal®) 100 mg Tablets; Drug: Nimodipine group

Nimodipine + Placebo

PLACEBO COMPARATOR

In the placebo arm, patients will receive standard care for aneurysmal subarachnoid hemorrhage, which must include nimodipine for the prevention of delayed cerebral ischemia (DCI) as per French and European guidelines. Nimodipine will be administered orally/enterally or intravenously, with dose, route, and duration decided by the treating physician according to patient status and local practice. Participants will receive a placebo, visually identical to cilostazol tablets, given orally or via gastric tube twice daily for 14 days, starting within 96 hours of hemorrhage onset. All other preventive or curative treatments for vasospasm or DCI-such as hypertensive therapy, milrinone, or endovascular procedures-are allowed at the physician's discretion. Monitoring, follow-up, and safety assessments will be performed in the same manner as in the experimental arm.

Drug: Placebo; Drug: Nimodipine group

Interventions

Cilostazol (Pletal®) 100 mg Tablets BIOLOGICAL

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.

Cilostazol + Nimodipine

Placebo DRUG

Oral or enteral placebo, visually identical to cilostazol, twice daily for 14 days, starting within 96 hours after hemorrhage onset.

Also known as: Placebo (matching Cilostazol)

Nimodipine + Placebo

Nimodipine group DRUG

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.

Cilostazol + Nimodipine; Nimodipine + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Cilostazol

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Caroline SCHIMPF, Doctor

  Chef de service Anesthésie - Réanimation GHU Paris - Neuro Sainte-Anne

  STUDY CHAIR

• Aurélien MAZERAUD, DOCTOR

  Anesthésie - Réanimation GHU Paris - Neuro Sainte-Anne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Khaoussou SYLLA, DR

CONTACT

01.45.65.76.78; K.SYLLA@ghu-paris.fr

OUIZA MANSEUR, Project manager

CONTACT

01 45 65 84 86; ouiza.manseur@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The CASH study is a phase III, multicenter, randomized, double-blind, placebo-controlled clinical trial with a parallel-group, adaptive sequential design. Adult patients admitted to intensive care within 96 hours of an aneurysmal subarachnoid hemorrhage (aSAH), and after successful aneurysm securing (clipping or coiling), are randomized into two groups. The experimental group receives cilostazol (100 mg twice daily for 14 days) in addition to standard nimodipine (21 days), while the control group receives placebo plus nimodipine. The primary objective is to assess neurological outcome at 6 months using the modified Rankin Scale. The total study duration is 49 months, including 42 months of enrollment and 6 months of follow-up. Two interim analyses are planned. The study is funded by a PHRC and monitored by an independent Data Safety Monitoring Board (DSMB).

Study Record Dates

• First Submitted: August 4, 2025
• First Posted: August 28, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): December 14, 2029
• Study Completion (Estimated): December 14, 2029
• Last Updated: September 10, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share