aSAH Treatment Based on Intraventricular ICP Monitoring: A Prospective, Multicenter, Randomized and Controlled Trial (ASTIM)

Aneurysmal Subarachnoid Hemorrhage Treatment Based on Intraventricular Intracranial Pressure Monitoring: A Prospective, Multicenter, Randomized and Controlled Trial

ASTIM is a multicenter, prospective, randomised, blinded end-point assessed trial, to investigate the efficacy and safety of treatment based on intracranial pressure monitoring in improving the prognosis of patients with aneurysmal subarachnoid hemorrhage.

Study Overview

• Status: Active, not recruiting
• Conditions: Aneurysmal Subarachnoid Hemorrhage; Intacranial Hypertension
• Intervention / Treatment: Device: Intraventricular intracranial pressure monitoring

Detailed Description

Subarachnoid hemorrhage (SAH) is a severe type of cerebral hemorrhage, characterized by a high mortality and disability rate, approximately 85% of SAH cases are attributed to ruptured intracranial aneurysms (RIAs), which is called aneurysmal SAH (aSAH). Improving the prognosis of patients with aSAH has become a pressing and significant issue.

The rupture of an aneurysm results in a significant amount of blood entering the subarachnoid space, triggering an increase in intracranial pressure (ICP). This escalated ICP, coupled with the compression from the hematoma, severely impairs brain tissue function, leading to a cascade of irreversible neurological impairments, such as abnormal blood pressure, respiratory arrest, and cardiac arrest. Systematic reviews and meta-analysis found that the incidence rate of elevated ICP (ICP > 20mmHg) in post-aSAH patients was 70.69%, with higher levels (according to the Hunt-Hess scale, WFNS scale, or modified Fisher grade) being more prevalent for increased ICP.

The utilization of Intraventricular ICP monitoring in patients with aSAH offers the advantage of obtaining real-time, accurate data on intracranial pressure, enabling more precise and timely control of cranial pressure. However, there is a dearth of high-level randomized controlled trial evidence supporting the use of ICP in the treatment of aSAH. Given the potential utility of ICP monitoring in aSAH management and its current lack of high-level evidence in evidence-based medicine, we intend to pursue the research.

• Study Type: Interventional
• Enrollment (Estimated): 372
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Department of Neurosurgery, Huashan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criterias

1. Definite diagnosis of aSAH: presence of SAH symptoms confirmed by CT, with rupture of an intracranial aneurysm identified by CTA or DSA. The ruptured aneurysm is scheduled for definitive treatment (clipping or endovascular therapy) within 72 hours of onset.
2. Age ≥ 18 years.
3. Symptom onset within 72 hours.
4. Hunt-Hess grade 2-4 and modified Fisher grade 2-4 on CT imaging.
5. Written informed consent obtained from the participant or legal representative.

Exclusion criteria included

1. Pregnancy or lactation;
2. Bilateral fixed dilated pupils on admission;
3. Malignancy, bleeding disorders, or other severe systemic comorbidities, including chronic obstructive pulmonary disease, multiple organ dysfunction, severe diabetes, heart failure, or chronic kidney disease;
4. Pre-existing neurological disability due to previous brain disease or neurosurgery, defined as a premorbid modified Rankin Scale (mRS) score ≥3;
5. Significant structural abnormalities on neuroimaging, such as extensive encephalomalacia or marked mass effect;
6. Subarachnoid haemorrhage caused by non-aneurysmal aetiologies;
7. Moyamoya disease associated aneurysmal rupture;
8. Other underlying diseases expected to substantially affect prognosis;
9. Active request for ICP monitoring by the patient or family;
10. Any other condition considered unsuitable for enrolment by two investigators;
11. Concurrent participation in another clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aSAH treatment based on Intraventricular ICP monitoring; In the acute phase of aSAH (following endovascular or craniotomy occlusion of the aneurysm), a ventricular ICP monitoring probe is surgically implanted. And the postoperative management of ICP is guided by quantifiable ICP parameters. The remaining treatments are consistent with those in the control group.	Device: Intraventricular intracranial pressure monitoring; The postoperative management of ICP is guided by quantifiable Intraventricular ICP parameters. The remaining treatments are consistent with those in the control group.
No Intervention: aSAH treatment without Intraventricular ICP monitoring; Only aSAH treatment surgery is performed without intraventricular ICP monitoring probe implantation. The treatment is not guided by ICP monitoring, and instead, aSAH treatment is conducted based on clinical signs and CT imaging to assess ICP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of good neurological functional prognosis	The proportion of patients with modified Rankin Scale (mRS) scores 0-2. The mRS is an ordinal hierarchical scale ranging from 0 to 6, with higher scores indicating more severe disability. A mRS ≤ 2 indicated a good clinical outcome, and a mRS 5-6 indicated a poor clinical outcome.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of good neurological functional prognosis	Proportion of patients with modified Rankin Scale (mRS) scores 0-2	30 days, 180days
The rate of good prognosis by Glasgow Outcome Scale-Extended (GOS-E)	The GOS-E is an ordinal hierarchical scale ranging from 1 to 8, with lower scores indicating more severe disability.	30 days, 90 days, 180days
Incidence of Delayed Cerebral Ischemia	Proportion of delayed cerebral ischemia occurring within 90 days.	90 days
Incidence of epilepsy	Proportion of symptomatic epilepsy occurring within 90 days.	90 days
All-cause mortality	Proportion of patients who died.	90 days
Incidence of hydrocephalus	Incidence of symptomatic hydrocephalus requiring surgical intervention	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rebleeding	Rebleeding related to aneurysmal rupture confirmed by imaging	90 days
Catheter tract haemorrhage	Catheter tract haemorrhage associated with ICP monitoring or external ventricular drainage	90 days
Intracranial infection	Intracranial infection, defined by clinical symptoms and cerebrospinal fluid findings consistent with infection, adjudicated by the Clinical Event Adjudication Committee	90 days
Wound-related complications	Wound-related complications, including infection, dehiscence, or cerebrospinal fluid leakage requiring intervention	90 days
Failure of ICP control	Defined as sustained intracranial hypertension requiring definitive surgical intervention, such as decompressive craniectomy	90 days
Symptomatic hydrocephalus	Symptomatic hydrocephalus requiring shunt surgery	90days
Seizures	Seizures confirmed clinically or by electroencephalography	90 days
Deep vein thrombosis	Deep vein thrombosis confirmed by imaging and requiring treatment	90 days
Severe sepsis or septic shock	Severe sepsis or septic shock resulting in organ dysfunction	90 days
Other unexpected serious adverse events		90 days

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Principal Investigator: Wei Zhu, Ph.D., Department of Neurosurgery, Huashan Hospital, Fudan University; Principal Investigator: Xuehai Wu, Ph.D., Department of Neurosurgery, Huashan Hospital, Fudan University

Publications and helpful links

General Publications

• Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017 Feb 11;389(10069):655-666. doi: 10.1016/S0140-6736(16)30668-7. Epub 2016 Sep 13.
• Etminan N, Chang HS, Hackenberg K, de Rooij NK, Vergouwen MDI, Rinkel GJE, Algra A. Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage According to Region, Time Period, Blood Pressure, and Smoking Prevalence in the Population: A Systematic Review and Meta-analysis. JAMA Neurol. 2019 May 1;76(5):588-597. doi: 10.1001/jamaneurol.2019.0006.
• Neifert SN, Chapman EK, Martini ML, Shuman WH, Schupper AJ, Oermann EK, Mocco J, Macdonald RL. Aneurysmal Subarachnoid Hemorrhage: the Last Decade. Transl Stroke Res. 2021 Jun;12(3):428-446. doi: 10.1007/s12975-020-00867-0. Epub 2020 Oct 19.
• Ironside N, Buell TJ, Chen CJ, Kumar JS, Paisan GM, Sokolowski JD, Liu KC, Ding D. High-Grade Aneurysmal Subarachnoid Hemorrhage: Predictors of Functional Outcome. World Neurosurg. 2019 May;125:e723-e728. doi: 10.1016/j.wneu.2019.01.162. Epub 2019 Feb 6.
• Seule M, Oswald D, Muroi C, Brandi G, Keller E. Outcome, Return to Work and Health-Related Costs After Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2020 Aug;33(1):49-57. doi: 10.1007/s12028-019-00905-2.
• Heuer GG, Smith MJ, Elliott JP, Winn HR, LeRoux PD. Relationship between intracranial pressure and other clinical variables in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2004 Sep;101(3):408-16. doi: 10.3171/jns.2004.101.3.0408.
• Robba C, Graziano F, Rebora P, Elli F, Giussani C, Oddo M, Meyfroidt G, Helbok R, Taccone FS, Prisco L, Vincent JL, Suarez JI, Stocchetti N, Citerio G; SYNAPSE-ICU Investigators. Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study. Lancet Neurol. 2021 Jul;20(7):548-558. doi: 10.1016/S1474-4422(21)00138-1.
• Hoh BL, Ko NU, Amin-Hanjani S, Chou SH-Y, Cruz-Flores S, Dangayach NS, Derdeyn CP, Du R, Hanggi D, Hetts SW, Ifejika NL, Johnson R, Keigher KM, Leslie-Mazwi TM, Lucke-Wold B, Rabinstein AA, Robicsek SA, Stapleton CJ, Suarez JI, Tjoumakaris SI, Welch BG. 2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2023 Jul;54(7):e314-e370. doi: 10.1161/STR.0000000000000436. Epub 2023 May 22.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): July 29, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: February 25, 2024
• First Submitted That Met QC Criteria: February 25, 2024
• First Posted (Actual): March 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Aneurysmal subarachnoid hemorrhage; Intraventricular intracranial pressure monitoring; Multicenter randomized clinical trail
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Subarachnoid Hemorrhage
• Other Study ID Numbers: KY2024-050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No