Léčba aneuryzmatického subarachnoidálního krvácení založená na monitorování intrakraniálního tlaku (ASTIM)
Léčba aneuryzmatického subarachnoidálního krvácení založená na monitorování intrakraniálního tlaku: multicentrická, randomizovaná, kontrolovaná studie
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.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
Subarachnoid hemorrhage (SAH) is a severe type of cerebral hemorrhage, characterized by high mortality and disability rates. Approximately 85% of SAH cases are caused by ruptured intracranial aneurysms and are classified as 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). Elevated ICP can impair cerebral perfusion and contribute to secondary brain injury and poor functional outcomes. A systematic review and meta-analysis found that the incidence rate of elevated ICP (ICP >20 mmHg) in patients with aSAH was 70.69%, with elevated ICP being more common in patients with higher disease severity grades, including higher Hunt-Hess, WFNS, or modified Fisher grades.
Intraventricular ICP monitoring provides continuous, real-time quantitative ICP data and may facilitate a stepwise ICP-lowering strategy and goal-directed management based on quantitative ICP values. However, the role of continuous ICP monitoring and protocolized ICP-targeted management in aSAH remains uncertain, and high-quality randomized evidence remains limited. Given this evidence gap, this study was designed to determine whether a structured management strategy guided by continuous intraventricular ICP monitoring improves functional outcomes in patients with aSAH compared with standard care, and to assess the safety of this management strategy.
Typ studie
Zápis (Aktuální)
Fáze
- Nelze použít
Kontakty a umístění
Studijní místa
-
-
Shanghai Municipality
-
Shanghai, Shanghai Municipality, Čína, 200000
- Department of Neurosurgery, Huashan Hospital, Fudan University
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion criterias
- 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.
- Age ≥ 18 years.
- Symptom onset within 72 hours.
- Hunt-Hess grade 2-4 and modified Fisher grade 2-4 on CT imaging.
- Written informed consent obtained from the participant or legal representative.
Exclusion criteria included
- Pregnancy or lactation;
- Bilateral fixed dilated pupils on admission;
- Malignancy, bleeding disorders, or other severe systemic comorbidities, including chronic obstructive pulmonary disease, multiple organ dysfunction, severe diabetes, heart failure, or chronic kidney disease;
- Pre-existing neurological disability due to previous brain disease or neurosurgery, defined as a premorbid modified Rankin Scale (mRS) score ≥3;
- Significant structural abnormalities on neuroimaging, such as extensive encephalomalacia or marked mass effect;
- Subarachnoid haemorrhage caused by non-aneurysmal aetiologies;
- Moyamoya disease associated aneurysmal rupture;
- Other underlying diseases expected to substantially affect prognosis;
- Active request for ICP monitoring by the patient or family;
- Any other condition considered unsuitable for enrolment by two investigators;
- Concurrent participation in another clinical trial.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Singl
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: aSAH management guided by continuous intraventricular ICP monitoring
In the acute phase of aSAH (following endovascular or microsurgical occlusion of the ruptured aneurysm), an intraventricular ICP catheter is placed for continuous ICP monitoring. Postoperative ICP management is guided by continuous quantitative ICP measurements according to a predefined ICP-targeted treatment protocol. Other guideline-based treatments are provided in the same manner as in the control group. |
The postoperative management of ICP is guided by continuous quantitative intraventricular ICP measurements according to a predefined ICP-targeted treatment protocol. The treatment target is ICP ≤20 mmHg, and a predefined stepwise ICP-lowering protocol is initiated if ICP remains >20 mmHg for more than 15 minutes. CSF drainage through the intraventricular catheter is permitted when clinically indicated. Other guideline-based treatments are provided in the same manner as in the control group. |
|
Žádný zásah: Guideline-based Standard Care Group
Guideline-based standard aSAH management is provided without continuous intraventricular ICP monitoring or the predefined ICP-targeted treatment protocol. ICP-related management is not guided by continuous quantitative ICP measurements and is instead based on clinical assessment, imaging findings, and treating physician judgment. Clinically indicated CSF diversion and other standard ICP-lowering treatments are permitted. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Favourable functional outcome at 3 months
Časové okno: 3 months after ictus
|
The proportion of patients with modified Rankin Scale (mRS) scores of 0-2. The mRS is an ordinal scale ranging from 0 to 6, with higher scores indicating greater disability. An mRS score of 0-2 is defined as a favourable functional outcome. |
3 months after ictus
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Favourable functional outcome assessed by mRS
Časové okno: 1 month and 6 months after ictus
|
Proportion of patients with mRS scores 0-2 |
1 month and 6 months after ictus
|
|
Favourable functional outcome assessed by Glasgow Outcome Scale-Extended (GOS-E)
Časové okno: 1 month, 3 months, and 6 months after ictus
|
The GOS-E is an ordinal scale ranging from 1 to 8, with lower scores indicating greater disability. A GOS-E score ≥5 is defined as a favourable functional outcome. |
1 month, 3 months, and 6 months after ictus
|
|
All-cause mortality
Časové okno: 1 month, 3 months, and 6 months after ictus
|
Proportion of patients who died. |
1 month, 3 months, and 6 months after ictus
|
|
Symptomatic hydrocephalus requiring permanent CSF shunting
Časové okno: 3 months after ictus
|
Proportion of patients with symptomatic hydrocephalus requiring ventriculoperitoneal or lumboperitoneal shunt placement. |
3 months after ictus
|
|
Delayed cerebral ischemia (DCI)
Časové okno: 3 months after ictus
|
Proportion of patients with DCI. DCI is defined according to the consensus criteria proposed by Vergouwen et al. Clinical DCI is defined as a new focal neurological impairment or a decrease of at least 2 points on the GCS, lasting for at least 1 hour, not apparent immediately after aneurysm occlusion, and not attributable to other causes. DCI-related cerebral infarction is defined as a new cerebral infarction identified on CT or MRI within 6 weeks after SAH that was absent on imaging obtained 24-48 hours after aneurysm occlusion and cannot be attributed to other causes. |
3 months after ictus
|
|
New-onset seizures
Časové okno: 3 months after ictus
|
Proportion of patients with clinically or electroencephalographically confirmed new-onset seizures. |
3 months after ictus
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Rebleeding
Časové okno: 3 months
|
New subarachnoid, intracerebral, or intraventricular haemorrhage attributable to rerupture of the index aneurysm after randomisation, confirmed by neuroimaging. |
3 months
|
|
Catheter tract haemorrhage
Časové okno: 3 months
|
New intraparenchymal or intraventricular haemorrhage along the trajectory of an intraventricular ICP monitoring catheter or EVD after catheter placement or removal, confirmed by CT, with an estimated haemorrhage volume ≥5 mL. |
3 months
|
|
Intracranial infection
Časové okno: 3 months
|
Intracranial infection meeting the prespecified microbiological and/or clinical cerebrospinal fluid criteria, with suspected events adjudicated according to the prespecified definition. |
3 months
|
|
Wound-related complications
Časové okno: 3 months
|
Infection, dehiscence, cerebrospinal fluid leakage, or other clinically significant wound complication at the ICP monitoring catheter or EVD insertion site requiring resuturing, procedural intervention, or prolonged wound care. |
3 months
|
|
Serious adverse events (SAEs)
Časové okno: 6 months
|
All serious adverse events are systematically recorded through completion of the 6-month follow-up. |
6 months
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Wei Zhu, Ph.D., Department of Neurosurgery, Huashan Hospital, Fudan University
- Vrchní vyšetřovatel: Xuehai Wu, Ph.D., Department of Neurosurgery, Huashan Hospital, Fudan University
Publikace a užitečné odkazy
Obecné publikace
- Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. doi: 10.1161/STROKEAHA.110.589275. Epub 2010 Aug 26.
- 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.
- Claassen J, Park S. Spontaneous subarachnoid haemorrhage. Lancet. 2022 Sep 10;400(10355):846-862. doi: 10.1016/S0140-6736(22)00938-2. Epub 2022 Aug 16.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- KY2024-050
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .