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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke
• Intervention / Treatment: Drug: Osmotic drugs

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.

• Study Type: Observational
• Enrollment (Estimated): 2592

Contacts and Locations

• Study Contact: Name: Suyue Pan, MD PH.D.; Phone Number: 13556184981; Email: pansuyue@smu.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
      • Contact: Shenggen Chen, M.D.; Phone Number: 13459480275
  • Guangdong
    • Dongguan, Guangdong, China
      • Dongguan People's Hospital
    • Dongguan, Guangdong, China
      • Dongguan Donghua Hospital
      • Contact: Lingyu Sun, M.D.; Phone Number: 13829203368
    • Guangzhou, Guangdong, China
      • Guangdong Provincial Hospital of Traditional Chinese Medicine
      • Contact: Lixin Wang, M.D.; Phone Number: 13922793886
    • Guangzhou, Guangdong, China
      • Huadu District People's Hospital of Guangzhou
      • Contact: Guangning Li, M.D.; Phone Number: 13926239656
    • Guangzhou, Guangdong, China
      • The Fourth Affiliated Hospital of Guangzhou Medical University
      • Contact: Wangchi Luo, M.D.; Phone Number: 13710895142
    • Heyuan, Guangdong, China
      • Heyuan People's Hospital
      • Contact: Minzhen Zhu, M.D.; Phone Number: 15007622318
    • Huizhou, Guangdong, China
      • Huizhou Municipal Central Hospital
      • Contact: Lizhi Wang, M.D.; Phone Number: 13802872076
  • Hainan
    • Haikou, Hainan, China
      • Haikou People's Hospital
      • Contact: Guoshuai Yang, M.D.; Phone Number: 13876006248
    • Haikou, Hainan, China
      • Hainan Traditional Chinese Medicine Hospital
      • Contact: Yong Gu, M.D.; Phone Number: 15521280288
    • Haikou, Hainan, China
      • Hainan People's Hospital
      • Contact: Fan Zhang, M.D.; Phone Number: 17389897580
  • Hunan
    • Changsha, Hunan, China
      • The First Hospital of Changsha
      • Contact: Xu Peng, M.D.; Phone Number: 15802507292
    • Hengyang, Hunan, China
      • The Second Hospital University of South China
      • Contact: Yanhong Hu, M.D.; Phone Number: 13265004191
    • Yueyang, Hunan, China
      • Yueyang People's Hospital
      • Contact: Yuan Zhou; Phone Number: 15107309796
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Sinopharm North Hospital
      • Contact: Lifei Xing, M.D; Phone Number: 15354919958
    • Hohhot, Inner Mongolia, China
      • The Affiliated Hospital of Inner Mongolia Medical University
      • Contact: Lihua Sun, M.D.; Phone Number: 18686292585
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • Ganzhou City People's Hospital
      • Contact: Zhaohui Lai, M.D.; Phone Number: 13879729792
  • Xinjiang
    • Kashgar, Xinjiang, China
      • Kashgar 1st People's Hospital
      • Contact: Qingbo Lu, M.D.; Phone Number: 13201186636
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Second Affiliated Hospital of Wenzhou Medical University
      • Contact: Saijun Zhou, M.D.; Phone Number: 13857746659

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Acute large hemispheric 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.

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Within 72 hours of onset of the stroke
3. Meets the diagnostic criteria for acute ischaemic stroke in the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018"
4. 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;
5. The patient consented and signed an informed consent form.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
trement group; Patient has used osmotic drugs within 72 hours of admission.	Drug: Osmotic drugs; Patients had used osmotic drugs within 72 hours of admission.
control group; Patient has not used osmotic drugs within 72 hours of admission.	Drug: Osmotic drugs; Patients had used osmotic drugs within 72 hours of admission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day mortality	Mortality within 90 days after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	90 days after onset
Incidence of acute renal impairment	Incidence of acute renal impairment after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	one year after onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day mRS	Modified Rankin Scale score within 90 days after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	90 days after onset
90-day mRS score change	Modified Rankin Scale score change within 90 days after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	90 days after onset
one year mRS	Modified Rankin Scale score within 1 year after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	1 year after onset
Incidence of early neurological deterioration	Incidence of early neurological deterioration within 30 days after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	30 days after onset
Incidence of malignant cerebral edema	Incidence of malignant cerebral edema within 1 year after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	1 year after onset
Clinical correction rate of brain herniation before decompressive hemicraniectomy	Clinical correction rate of brain herniation before decompressive hemicraniectomy	Up to 3 days
Incidence of need for decompressive hemicraniectomy	Incidence of need for decompressive hemicraniectomy after onset	up to 24 hours
The actual incidence of decompressive hemicraniectomy	The actual incidence of decompressive hemicraniectomy after onset	up to 24 hours
Incidence of Symptomatic intracranial hemorrhage	Incidence of Symptomatic intracranial hemorrhage within 1 year after onset in patients with large hemispheric infarction who were eligible for inclusion criteria	up to 24 hours
Incidence of drug-related adverse events	Incidence of adverse events due to drugs within 1 year after the onset of large hemispheric infarction in patients who met the inclusion criteria	up to 24 hours

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Second Affiliated Hospital of Guangxi Medical University; Guangdong Provincial Hospital of Traditional Chinese Medicine; Fujian Medical University Union Hospital; Second Affiliated Hospital of Wenzhou Medical University; Dongguan People's Hospital; Huizhou Municipal Central Hospital; The Affiliated Hospital of Inner Mongolia Medical University; Hainan People's Hospital; Huadu District People's Hospital of Guangzhou; The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine; Kashgar 1st People's Hospital; The Second Hospital University of South China; Haikou People's Hospital; Ganzhou City People's Hospital; The Fourth Affiliated Hospital of Guangzhou Medical University; Sinopharm North Hospital; Hainan Traditional Chinese Medicine Hospital
• Investigators: Principal Investigator: Suyue Pan, Department of Neurology, Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; large hemispheric infarction; osmotic drugs
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Infarction
• Other Study ID Numbers: NFEC-2023-039

Drug and device information, study documents

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