Severe Stroke
Conditions
Brief summary
This study is a exploratory, randomized, controlled, open-label, blinded-endpoint Phase II clinical trial designed to evaluate whether delaying antihyperglycemic treatment for 72 hours improves neurological outcomes in patients with severe stroke and hyperglycemia. A total of 426 patients with severe stroke (including ischemic stroke, intracerebral hemorrhage, or aneurysmal subarachnoid hemorrhage) within 24 hours of onset and blood glucose \>10 mmol/L at randomization will be enrolled. Participants will be randomly assigned in a 1:1 ratio to either delayed antihyperglycemic treatment (initiated on Day 4) or early antihyperglycemic treatment (initiated on Day 1). Glycemic control targets (7.8-10.0 mmol/L) and insulin therapy follow current clinical guidelines. The primary outcome is the incidence of poor functional outcome (modified Rankin Scale score ≥ 3) at 90 days. Secondary outcomes include mortality, NIHSS score, GCS score, ICU length of stay, and safety events such as hypoglycemia and infections. The study aims to provide evidence on the optimal timing of glycemic control in severe stroke patients with stress hyperglycemia.
Interventions
Insulin administered intravenously to maintain blood glucose between 7.8-10.0 mmol/L. Timing of initiation differs by arm: Day 1 for early group, Day 4 for delayed group.
Sponsors
First Affiliated Hospital of Wannan Medical College
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years; 2. Severe stroke within 24 hours of onset, meeting one of the following criteria: 1）Severe ischemic stroke: Glasgow Coma Scale (GCS) score ≤ 12 or National Institutes of Health Stroke Scale (NIHSS) score ≥ 15 or CT hypodensity \> 1/3 of middle cerebral artery (MCA) territory; 2）Severe intracerebral hemorrhage: Supratentorial hematoma volume ≥ 30 mL (thalamic hemorrhage ≥ 10 mL) or infratentorial hematoma volume ≥ 10 mL (brainstem hemorrhage ≥ 5 mL); 3）Aneurysmal subarachnoid hemorrhage; 3. Blood glucose level \> 10 mmol/L at randomization; 4. Signed informed consent.
Exclusion criteria
1. Known history of type 1 diabetes mellitus; 2. Known allergy to insulin or diagnosis of insulinoma; 3. Pre-stroke modified Rankin Scale (mRS) score \> 1; 4. Hemodynamic instability refractory to medical treatment (systolic blood pressure \< 90 mmHg or diastolic blood pressure \< 60 mmHg); 5. Decompensated heart failure (New York Heart Association \[NYHA\] class III or IV); 6. Estimated glomerular filtration rate (eGFR) \< 30 mL/min; 7. Expected survival \< 90 days due to malignancy; 8. Participation in another drug or device clinical trial within the past 30 days; 9. Women of childbearing potential who refuse to use effective contraception despite negative pregnancy test, pregnant women, or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Poor Functional Outcome at 90 Days | from enrollment to day 90 post-enrollment | Proportion of patients with modified Rankin Scale (mRS) score ≥ 3, assessed at 90 days post-randomization. The mRS is a 7-point scale ranging from 0 (no symptoms) to 6 (death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality at ICU Discharge or Day 14 | from admission to ICU discharge within 14 days | Proportion of patients who die from any cause by ICU discharge or Day 14, whichever occurs first |
| Neurological Status at ICU Discharge or Day 14 | from admission to ICU discharge within 14 days | Neurological function assessed by National Institutes of Health Stroke Scale (NIHSS) score. NIHSS ranges from 0 to 42, with higher scores indicating more severe neurological deficits |
| Level of Consciousness at ICU Discharge or Day 14 | from admission to ICU discharge within 14 days | Level of consciousness assessed by Glasgow Coma Scale (GCS) score. GCS ranges from 3 to 15, with lower scores indicating impaired consciousness |
| All-cause Mortality at 90 Days | from admission to discharge at 90 days | Proportion of patients who die from any cause within 90 days post-randomization |
| Length of ICU Stay | From admission to ICU discharge, an average of 11 days | Total duration of intensive care unit (ICU) hospitalization, measured in days |
| Incidence of Adverse Events | From randomization to ICU discharge or Day 14, whichever occurs first | Proportion of patients experiencing adverse events during ICU stay, including hypoglycemia (random blood glucose \< 3.3 mmol/L), symptomatic hypoglycemia, pulmonary infection, urinary tract infection, and electrolyte disturbances |
| Incidence of Serious Adverse Events | From randomization to 90 day post-randomization | Proportion of patients experiencing serious adverse events, defined as any event resulting in death, disability, congenital anomaly, or severe hypoglycemia (random blood glucose \< 2.22 mmol/L) requiring prolonged hospitalization or re-admission |
Outcome results
None listed