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.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Stroke
• Intervention / Treatment: Drug: Intravenous insulin

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delayed Antihyperglycemic Group; Antihyperglycemic treatment is delayed for 72 hours after enrollment. Insulin therapy is initiated on Day 4 targeting blood glucose 7.8-10.0 mmol/L until ICU discharge or Day 14.	Drug: Intravenous insulin; 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.
Active Comparator: Early Antihyperglycemic Group; Antihyperglycemic treatment is initiated on Day 1. Insulin therapy targets blood glucose 7.8-10.0 mmol/L until ICU discharge or Day 14.	Drug: Intravenous insulin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Poor Functional Outcome at 90 Days	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).	from enrollment to day 90 post-enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality at ICU Discharge or Day 14	Proportion of patients who die from any cause by ICU discharge or Day 14, whichever occurs first	from admission to ICU discharge within 14 days
Neurological Status at ICU Discharge or Day 14	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	from admission to ICU discharge within 14 days
Level of Consciousness at ICU Discharge or Day 14	Level of consciousness assessed by Glasgow Coma Scale (GCS) score. GCS ranges from 3 to 15, with lower scores indicating impaired consciousness	from admission to ICU discharge within 14 days
All-cause Mortality at 90 Days	Proportion of patients who die from any cause within 90 days post-randomization	from admission to discharge at 90 days
Length of ICU Stay	Total duration of intensive care unit (ICU) hospitalization, measured in days	From admission to ICU discharge, an average of 11 days
Incidence of Adverse Events	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	From randomization to ICU discharge or Day 14, whichever occurs first
Incidence of Serious Adverse Events	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	From randomization to 90 day post-randomization

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wannan Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 202603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No