Delayed Versus Early Antihyperglycemic Treatment for Severe Stroke

Delayed Versus Early Antihyperglycemic Treatment for Severe Stroke: A Prospective, Randomized, Controlled, Open-Label, Blinded-Endpoint Clinical Trial

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.

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.