Association of Osmotic Drugs With Clinical Outcomes in Acute Large Hemispheric Infarction

Official title

Association of Osmotic Drugs With Clinical Outcomes in Acute Large Hemispheric Infarction: a Prospective, Multicenter, Observational Cohort Study

Overview

Stroke remains the second leading cause of death worldwide, with 2%-8% of these being large hemispheric infarction (LHI) with an occupying effect and the worst prognosis. Even with medical and surgical treatment, the mortality of LHI with cerebral edema is as high as 20% to 30%. Current guidelines recommend supportive supervision, osmotic drugs, and decompressive hemicraniectomy (DHC) for the treatment of LHI, but not all patients with LHI are suitable for DHC, and not all of them can afford the high cost of DHC. In the real-world, the use of osmotic drugs is more common than DHC. The guideline recommends using mannitol or hypertonic saline to reduce cerebral edema and tissue displacement in patients with cerebral edema. Mannitol is the most widely used and longest-standing osmotic drug, and since 1965, hypertonic saline has been used to treat intracranial hypertension. Most of the previous studies compare the efficacy of DHC over medical therapy or compare the efficacy of mannitol with hypertonic saline, but there is an absence of clinical data on whether osmotic drug therapy can improve the clinical prognosis of patients with large hemispheric infarction at 90 days or even longer. Therefore, the purpose of this study was to investigate the association between the osmotic drug and clinical outcomes in large hemispheric infarction, with the aim of informing clinical decisions.

Detailed description

Diagnostic criteria for large hemispheric infarction (LHI): CT within 6 hours of onset showing hypointense areas \> 1/3 of the middle cerebral artery territory, or hypointense areas \> 50% of the middle cerebral artery territory within 6 hours to 72h of onset. LHI is strongly associated with severe cerebral edema, which can occur to varying degrees cerebral edema within hours or days of LHI. In recent years, endovascular treatment has significantly improved the revascularization of patients with large vessel occlusive cerebral infarction and reduced the incidence of malignant progression and mortality in patients with acute LHI, but many patients still suffer from malignant brain edema (MBE), which leads to the worsening of the disease.

Interventions

• Drug Osmotic drugs
  Patients had used osmotic drugs within 72 hours of admission.

Primary outcome measures

• 90-day mortality [Time frame: 90 days after onset]
• Incidence of acute renal impairment [Time frame: one year after onset]

Secondary outcome measures (10)

• 90-day mRS [Time frame: 90 days after onset]
• 90-day mRS score change [Time frame: 90 days after onset]
• one year mRS [Time frame: 1 year after onset]
• Incidence of early neurological deterioration [Time frame: 30 days after onset]
• Incidence of malignant cerebral edema [Time frame: 1 year after onset]
• Clinical correction rate of brain herniation before decompressive hemicraniectomy [Time frame: Up to 3 days]
• Incidence of need for decompressive hemicraniectomy [Time frame: up to 24 hours]
• The actual incidence of decompressive hemicraniectomy [Time frame: up to 24 hours]
• Incidence of Symptomatic intracranial hemorrhage [Time frame: up to 24 hours]
• Incidence of drug-related adverse events [Time frame: up to 24 hours]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Within 72 hours of onset of the stroke
• Meets the diagnostic criteria for acute ischaemic stroke in the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018"
• Meeting the diagnostic criteria for massive cerebral infarction in the "Guidelines for the Surgical Treatment of Massive Cerebral Infarction": CT within 6 hours of onset showing hypointense areas > 1/3 of the middle cerebral artery territory, or > 50% of the middle cerebral artery territory within 6 hours to 72 hours of onset;
• The patient consented and signed an informed consent form.

Exclusion criteria

• Women who are pregnant or breastfeeding;
• in combination with other serious comorbidities resulting in a life expectancy of less than 3 months
• Those who are allergic or intolerant to osmotic drugs;
• Those who have participated in other interventional clinical studies (which affecting the observation of outcomes in this cohort);
• Those with a previous history of stroke and significant residual neurological disability (mRS ≥ 2 points)
• Those who, in the judgment of the investigator, are not suitable for participation in this study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 19 centers

• Fujian Medical University Union Hospital — Fuzhou
• Dongguan donghua hospital — Dongguan
• Dongguan People's Hospital — Dongguan
• Guangdong Provincial Hospital of Traditional Chinese Medicine — Guangzhou
• Huadu District People's Hospital of Guangzhou — Guangzhou
• The Fourth Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Heyuan people's Hospital — Heyuan
• Huizhou Municipal Central Hospital — Huizhou
• … and 11 more centers

Identifiers

NCT: NCT05914272 · NFEC-2023-039

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗