Clinical trial NCT04419337: Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Patients With Stroke
Official title: Comparison of Combined Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Diabetic Patients With Ischemic Stroke: Rationale and Study Design
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diabetes Mellitus
Stroke
Keywords: stroke
diabetes mellitus
sodium-glucose transport protein 2 inhibitor
pioglitazone
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital
name: Chiayi Christian Hospital
name: Tainan Sin-lau Hospital
First posted: 2020-06-05
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: HbA1C
timeFrame: 6 months from baseline in active vs control arms
Secondary outcomes:
measure: UACR
timeFrame: 6 months from randomization in active vs control arms
measure: hs-CRP
timeFrame: 6 months from randomization
measure: NT-proBNP
timeFrame: 6 months from randomization
measure: insulin resistance
timeFrame: 6 months from randomization
Other outcomes:
Locations:
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital, Chiayi Branch
Study officials:
affiliation: Chang Gung Memorial Hospital, Chiayi Branch
name: Meng Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: