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

Phase 3

• Conditions: Hyperglycemia; Acute Stroke
• Interventions: Drug: Insulin Glargine; Drug: Regular Insulin

• Registration Number: NCT02607943
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-11-04
• Study First Submitted QC: 2015-11-17
• Study First Posted: 2015-11-18
• Study Start: 2015-12
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-17
• Last Update Posted: 2016-08-19
• Primary Completion: 2018-07
• Study Completion: 2018-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin Glargine	Insulin Glargine	subcutaneous long acting basal insulin (insulin glargine) with added short acting regular insulin to correct hyperglycemic events
Regular Insulin	Regular Insulin	short acting regular insulin pre-meal with added NPH at bed time if start eating

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Good functional outcome at 3 months post stroke	3 months after stroke	Good functional outcome is defined as modified Rankin Scale \<2
Stroke in evolution	one week after stroke onset	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.
Blood glucose variability via continuous glucose monitoring	72 hours after recruitment	Blood glucose is monitored 24 hours per day via continuous glucose monitoring for 72 hours after recruitment to evaluate the variability.
Blood biomarkers	72 hours after recruitment	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
Urine biomarkers	72 hours after recruitment	Urine biomarkers include catecholamines such as normetanephrine and vanillylmandelic acid (VMA)

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan