Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Patients With Stroke

Stroke Clinical Trial

Official title:

Comparison of Combined Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Diabetic Patients With Ischemic Stroke: Rationale and Study Design

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04419337
• Other study ID #: MOST 108-2314-B-182-017-
• Status: Recruiting
• Phase: Phase 2
• Start date: September 15, 2019
• Est. completion date: January 31, 2024

Study information

• Verified date: March 2023
• Source: Chang Gung Memorial Hospital
• Contact: Meng Lee, MD
• Phone: 8863621000
• Email: menlee5126[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction: An optimal combination of antidiabetic drugs for diabetic patients with ischemic stroke is not well-established. The objective of this randomized trial is to evaluate whether combination of pioglitazone and a sodium glucose cotransporter 2 (SGLT-2) inhibitor, compared with a dipeptidyl peptidase-4 (DPP-4) inhibitor, reduces recurrent stroke in diabetic patients with recent ischemic stroke.

Methods and analysis: The trial is a randomized, parallel-group study conducted at 7 hospitals in Taiwan. Inclusion criteria are adult patients with a history of ischemic stroke within 3 months, diabetes mellitus with Hba1C > 7%, taking metformin currently or previously, and estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2. Eligible patients who sign the informed consent forms will be randomly assigned in a 1:1 ratio to receive either combination of pioglitazone and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) vs. a DPP4 inhibitor. Primary outcome is change in HbA1C between 6 months and baseline in active vs comparator groups. Additional biomarker outcomes are change in hs-CRP insulin resistance, B type natriuretic peptide, and urine albumin creatinine ratio between 6 months and baseline.

Ethics and dissemination Study protocol was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Chiayi Branch, Taiwan (201702353A3, 201802340A3 and 201902176A3). All participants will be required to sign and date an informed consent form. Study findings will be disseminated via a peer-reviewed journal.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 31, 2024
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Ischemic stroke within 3 months of randomization

2. Type 2 diabetes mellitus and Hba1C > 7.0% and under metformin therapy currently or previously

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. Irreversible medical conditions with predicted survival < 1 years

5. Current use of an insulin

6. Current use of a glucagon-like peptide-1 receptor agonist

7. Current use of pioglitazone or an SGLT-2 inhibitor

Related Conditions & MeSH terms

• Diabetes Mellitus
• Stroke

Intervention

Drug:
• Metformin plus Pioglitazone plus an SGLT2 inhibitor
Patients assigned to active group will stop their prior oral antidiabetic drugs and receive combination of metformin, pioglitazone, and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) and dose will be adjusted by their physicians.

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital, Chiayi Branch	Chiayi City

Sponsors (4)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital	Chiayi Christian Hospital, National Taiwan University Hospital, Tainan Sin-lau Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1C	blood test to evaluate glycemic control	6 months from baseline in active vs control arms
Secondary	UACR	to evaluate microalbuminuria	6 months from randomization in active vs control arms
Secondary	hs-CRP	to evaluate hs-CRP in active vs control arms	6 months from randomization
Secondary	NT-proBNP	to evaluate NT-proBNP in active vs control arms	6 months from randomization
Secondary	insulin resistance	Insulin resistance will be evaluated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	6 months from randomization