Status and phase
Conditions
Treatments
About
Type 2 diabetes mellitus (T2DM) is one of the most important risk factors for atherosclerotic heart disease. Strategies focused solely on glycemic control have failed to demonstrate vascular events reduction in this population. On the other hand, new antidiabetic drugs recently have demonstrated significant decrease of cardiovascular mortality, raising the hypothesis that possible effects beyond glycemia control could explain this benefit. Aim: This study is intended to evaluate possible pleiothropic effects of dapaglifozin, a SGLT-2 (sodium glucose cotransporter 2) inhibitor, in individuals admitted with a diagnosis of Acute Myocardial Infarction (AMI). Methods: This is a prospective, randomized, double-blind, placebo controlled trial. Individuals presenting with AMI whithin the first seven days of evolution will be randomized to dapaglifozin or placebo. The investigators's goal is to analyze platelet aggregability 48 hours after randomization (primary endpoint), as well as glycemic control, cardiac biomarkers, corrected QT interval electrocardiographic analysis, autonomic modulation through spectral analysis of the RR interval and inflammatory biomarkers at inclusion and 30 days after starting study drug (secondary endpoints). Sample size calculation resulted in 80 individuals (40 per group). Expected results: This study will seek to aggregate new insights to the current knowledge about this new antidiabetic drug class. Previous randomized clinical trials have demonstrated that SGLT-2 inhibitors significantly reduced the composite endpoint of cardiovascular death, AMI or stroke, as well as Heart Failure (HF) hospitalization. Therefore, this study is supposed to clarify possible mechanisms that could explain these results aforementioned.
Full description
Study design: Single-center, prospective, randomized, double-blind, placebo-controlled, parallel-group clinical study.
Primary Outcome: To compare platelet aggregation in the dapagliflozin and placebo groups by the Multiplate Analyzer® test (using ADP as an agonist) in hospitalized patients with a diagnosis of AMI within seven days of evolution, using dual antiplatelet therapy with acetylsalicylic acid (ASA) and an anti-platelet ADP, 48 ± 12 hours after starting dapagliflozin/placebo treatment. Due to the rapid oral absorption of the medication, reaching maximum plasma concentration after 2 hours and as its pharmacokinetics does not change with food or other concomitant medications, our hypothesis is that there may be an antiplatelet effect that can be detected early
Other exploratory analyses:
Analyze the primary objective of the study in the following pre-specified subgroups:
Study plan: Eligible patients will be enrolled within the first seven days of symptom onset. After signing the Informed Consent Form, laboratory tests will be collected, as previously specified in the methodology. Subsequently, patients will be randomized to use dapagliflozin or placebo in a double-blind manner. Randomization will be performed using the Graphipad® program, with distribution of numbered vials containing the study medication (dapagliflozin 10 mg tablets or placebo-equivalent), randomly between the two groups. All patients must be using dual antiplatelet therapy and the results will be stratified by the type of treatment performed for AMI. Study medication, once initiated, will be maintained until the final platelet assessment, scheduled for 30 days, is performed. The other medications, including other oral antidiabetics and insulin, will be used according to the institution's routines, except for prohibited medications, as stated in the exclusion criteria. After the end of the study, the sealed envelopes will be opened to identify the blinding codes.
Glycemic control: According to institutional routines, the cut-off value of 140 mg/dL will be used in two sequential capillary blood glucose levels as the threshold for starting treatment with subcutaneous insulin. Patients whose diabetes control is not adequate, as evidenced by a capillary blood glucose value maintained greater than 250 mg/dL, will receive the intravenous insulin protocol, also in accordance with the institutional routines (summary below).The HbA1c target will be of < 7.5%.
Inclusion criteria:
Exclusion criteria:
Casuistry: To calculate the sample size, the following assumptions were taken into account consideration :
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
80 participants in 2 patient groups, including a placebo group
Loading...
Central trial contact
Jose JN Nicolau
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal