Insulin Glargine Versus Regular Insulin Based Regimens in Glycemic Control After Acute Stroke (ICAS)

Insulin Glargine Versus Regular Insulin Based Regimens in Glycemic Control After Acute Stroke: A Multi-center, Randomized Control Study

Hyperglycemia is common during acute ischemic stroke. However, the optimal strategy to control hyperglycemia during acute ischemic stroke has not been established. The object of this multicenter randomized controlled study is to determine the efficacy and safety of early initiation of subcutaneous once-daily insulin glargine, in comparison with regular insulin, based on a protocolized sliding scale regimen to achieve proper sugar control in acute stroke patients with hyperglycemia admitted to the intensive care unit.

Study Overview

• Status: Unknown
• Conditions: Hyperglycemia; Acute Stroke
• Intervention / Treatment: Drug: Insulin Glargine; Drug: Regular Insulin

Detailed Description

Study Rationale: Hyperglycemia is common during acute ischemic stroke. It has been shown that persistent in-hospital hyperglycemia during the first 24 hours (h) after stroke is associated with worse outcomes than normoglycemia. However, the optimal strategy to control hyperglycemia during acute ischemic stroke has not been established.

Aims: The object of this multicenter randomized controlled study is to determine the efficacy and safety of early initiation of subcutaneous once-daily insulin glargine, in comparison with regular insulin, based on a protocolized sliding scale regimen to achieve proper sugar control in acute stroke patients with hyperglycemia admitted to the intensive care unit (ICU).

Design: This is a 3-year, randomized, multicenter trial. Approximate 120 hyperglycemic acute stroke patients will receive either (a) subcutaneous long acting basal insulin (insulin glargine) with added short acting regular insulin to correct hyperglycemic events or (b) short acting regular insulin pre-meal with added NPH at bed time if start eating, for 72 h, starting within 24 h of stroke symptom onset. The inclusion criteria are patients who admitted to stroke ICU within 24 hours of acute stroke onset and have repeated random blood glucose >200 mg/dL with a 2 hours interval. The exclusion criteria include patients with age <20 years, pregnancy, shock, severe infection, end stage renal disease requiring dialysis, type I DM or current steroid usage. Capillary blood glucose will be measured every 4-hours to adjust the next insulin dose. Glucometric parameters will also be analyzed by continuous blood glucose monitoring system. 10 ml blood and same amount of urine from 24 hours urine collection will be collected every day for further measurement of a variety of blood inflammatory markers and urine catecholamine levels.

Study outcomes: The primary endpoint is the percentage of time in the range of 80-180 mg/dL during the sugar monitoring period. The secondary endpoints include: (1) good functional outcome at 3 months post stroke (modified Rankin Scale <2), (2) stroke in evolution, (3) 24 hours blood glucose variability via continuous glucose monitoring, and (4) blood and urine biomarkers.

In summary, this trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia. It will determine the potential benefits and risks of application of long acting basal insulin during very early stage of acute stroke.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Sung-Chun Tang, MD. PhD; Phone Number: 63280 +88623123456; Email: tangneuro@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who admitted to stroke ICU within 24 hours of acute stroke onset and have repeated random blood glucose >200 mg/dL with a 2 hours interval

Exclusion Criteria:

• Patients with age <20 years,
• pregnancy,
• shock, severe infection, end stage renal disease requiring dialysis,
• type I DM or current steroid usage.

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: Insulin Glargine; subcutaneous long acting basal insulin (insulin glargine) with added short acting regular insulin to correct hyperglycemic events	Drug: Insulin Glargine; Insulin Glargine Versus Regular Insulin Based Regimens in Glycemic Control; Other Names: Lantus
Active Comparator: Regular Insulin; short acting regular insulin pre-meal with added NPH at bed time if start eating	Drug: Regular Insulin; Insulin Glargine Versus Regular Insulin Based Regimens in Glycemic Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of time in the range of 80-180 mg/dL during the sugar monitoring period	72 hours after recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Good functional outcome at 3 months post stroke	Good functional outcome is defined as modified Rankin Scale <2	3 months after stroke
Stroke in evolution	Stroke in evolution is defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 2 points excluding other attributable medical or systemic causes.	one week after stroke onset
Blood glucose variability via continuous glucose monitoring	Blood glucose is monitored 24 hours per day via continuous glucose monitoring for 72 hours after recruitment to evaluate the variability.	72 hours after recruitment
Blood biomarkers	Blood biomarkers include soluble form of receptor for glycation end-product (sRAGE), high mobility group box 1(HMGB1), heat shock protein 70 (HSP 70), C-reactive protein (CRP), D-dimer, fibrinogen	72 hours after recruitment
Urine biomarkers	Urine biomarkers include catecholamines such as normetanephrine and vanillylmandelic acid (VMA)	72 hours after recruitment

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Chang Gung Memorial Hospital; Taipei Medical University Shuang Ho Hospital
• Investigators: Principal Investigator: Jiann-Shing Jeng, MD. PhD, National Taiwan University Hospital

Publications and helpful links

General Publications

• Tang SC, Shih SR, Lin SY, Chen CH, Yeh SJ, Tsai LK, Yang WS, Jeng JS. A randomized trial to investigate the efficacy and safety of insulin glargine in hyperglycemic acute stroke patients receiving intensive care. Sci Rep. 2021 Jun 1;11(1):11523. doi: 10.1038/s41598-021-91036-2.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: November 17, 2015
• First Posted (Estimate): November 18, 2015

Study Record Updates

• Last Update Posted (Estimate): August 19, 2016
• Last Update Submitted That Met QC Criteria: August 17, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: hyperglycemia; long-acting insulin; acute stroke; regular insulin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hyperglycemia; Stroke; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: 201504075MINC