Antidiabetic Triple Therapy Effects on Surrogate Tests After Stroke

• Status: Recruiting
• Trial end date: 2023-01-31
• Target enrollment: 0
• Participant gender: All

Summary

Background: Diabetes mellitus is a major risk factor of ischemic stroke. It is unsettled issue for which antidiabetic drugs is the best strategy for stroke patients with diabetes mellitus. Therefore it is important to figure out the most efficient way to prevent cardiovascular event in stroke patients. High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation and its level can independently predict risk of cardiovascular disease and can be used as a surrogate for future cardiovascular event.

Objective: To clarify whether triple therapy with combination with metformin, pioglitazone, and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) for 6 months can reduce hsCRP in stroke patients with diabetes mellitus.

Methods: This study will be conducted in 8 hospitals in Taiwan, enrolling 200 patients. Inclusion criteria were ischemic stroke within 6 months, having diabetes with Hb1c > 7%, eGFR > 45, no history of heart failure or amputation, and willing to sign informed consent. Patients will be randomly assigned to active treatment and conventional groups. In active arm, physicians will prescribe metformin, pioglitazone, and an SGLT2 inhibitor. In control arm, physicians will prescribe antidiabetic drug based on their personal experience. Treatment duration will be 6 months. The primary endpoint is hsCRP change from baseline in active vs control arm. The secondary endpoints are insulin resistance, BNP, albuminuria change from baseline in active vs control arm.

Expectation: IF combination therapy with metformin, pioglitazone, and an SGLT2 inhibitor is able to reduce inflammation and other biomarkers, such approach can be considered as priority therapy for ischemic stroke patients with diabetes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chang Gung Memorial Hospital
• Collaborators: Chiayi Christian Hospital; National Taiwan University Hospital
• Treatments: Metformin; Pioglitazone; Sodium-Glucose Transporter 2 Inhibitors

Criteria

Inclusion Criteria:

1. Ischemic stroke within 6 months of randomization

2. Type 2 diabetes mellitus and Hba1C > 7.0% and under metformin currently or previously with or without other antidiabetic drugs

3. Estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m2

4. Age ≥ 20 y at study entry

5. Ability and willingness to provide informed consent

Exclusion Criteria:

1. History of congestive heart failure (NYHA class 1-4)

2. History of bladder cancer

3. History of repeated (> 2 episodes) urinary tract infection or genital tract infection

4. History of amputation

5. Irreversible medical conditions with predicted survival < 1 years

6. ALT > 100 mg/dl

7. Currently use insulin injection to control blood glucose

8. Currently use Glucagon-like peptide-1 receptor agonist to control blood glucose

9. Currently use pioglitazone or SGLT-2 inhibitor