Effect of Empagliflozin as adjunctive therapy versus placebo on serum level of oxidative stress biomarkers in diabetic patients with systolic heart failure: a double-blind randomized clinical trial

To assess the effect of Empagliflozin as adjunctive therapy versus placebo on serum level of oxidative stress biomarkers in diabetic patients with systolic heart failure

This is a Phase III double-blind randomized clinical trial with a control group, in which eligible patients will be randomly assigned to the intervention and control groups using block randomization.

This study will be conducted at the Farshchian Heart Hospital in Hamadan city, involving 80 eligible diabetic patients with systolic heart failure. The patients will be randomly assigned to the intervention and control groups through the block randomization. This trial will be double-blinded.

Inclusion criteria: Age 18 to 80 years Type 2 diabetes Controlled systolic heart failure for at least 6 months Hemoglobin A1c less than 6.5 Stable clinical and hemodynamic status Exclusion criteria: Pregnancy or breastfeeding Inflammatory, respiratory, infectious or malignant diseases History of myocardial infarction, stroke, angioplasty or CABG in the last 3 months Embedding Pacemaker in the last 3 months Use of anti-oxidant or anti-inflammatory drugs or corticosteroids in the last 3 months

Intervention group: Routine treatment plus tablet Empagliflozin 10 mg (manufactured by Abidi Pharmaceutical Co.) daily for 3 months Control group: Routine treatment plus tablet placebo (manufactured by Abidi Pharmaceutical Co.) daily for 3 months

Primary outcome: Serum levels of oxidative stress factors (malonaldehyde, superoxide dismutase, glutathione peroxidase), serum iron level, serum transferrin level, serum ferritin level

In this study, random assignment of patients to the intervention and control groups will be carried out using block randomization. To achieve this, four sheets of paper will be prepared - two with the name of the intervention and two with the name of the control. These paper sheets will be pooled and placed in a container. Patients will be selected one at a time without replacement, and for each patient, a paper sheet will be randomly drawn from the container. After each draw, the paper sheets will be returned to the container, and the process will be repeated until the desired sample size is reached.

Both the medications and placebos will have the same shape. Consequently, patients will remain unaware of the type of intervention they receive. Moreover, the randomization process will be conducted by a separate individual from the one who examines the patients, ensuring that the examining person remains unaware of the intervention. The analyzer responsible for evaluating the trial's results will also be kept blind to the type of interventions. Therefore, the trial will be conducted as a double-blind study.