Dapagliflozin in Patients With Atrial Fibrillation (DAPA-AF)

Study Overview
=================
Brief Summary
-----------------
The study will investigate the effect of Dapagliflozin on atrial fibrillation (AF) burden. AF burden will be defined as the percent of time spent in AF over a 2-week period, assessed by noninvasive continuous heart rhythm monitoring at baseline and at 3 months, quality of life (QOL) and validated echocardiographic indices of atrial myopathy. This knowledge will enable us to study the therapeutic potential of SGLT2i as a novel adjunct treatment for patients with DM and AF. Patients with paroxysmal AF (AF that terminates spontaneously or with intervention within seven days of onset) and DM and randomize them to Dapagliflozin or placebo. Continuous heart rhythm monitoring patch for AF burden will be used, measure of QOL with the help of AF Effect on Quality-of-life survey and perform an echocardiogram with measurement of left atrial volume index, left atrial strain and atrial tissue dopplers. All measurements will be performed at baseline and at study completion. The central hypothesis is that SGLT2i will lead to reduced AF burden that will translate into improvement in QOL, and the underlying mechanism is improvement in atrial myopathy.

Detailed Description
-----------------
Patients with diabetes mellitus (DM) and atrial fibrillation (AF) represent a high-risk cohort that is at an increased risk of cardiovascular complications as compared to AF patients without DM. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of diabetic drugs and large clinical trials have established their multiple cardiovascular benefits. However, none of these clinical trials studied AF as a primary outcome. SGLT2i have multiple properties that can be protective against AF and the role of SGLT2i in preventing recurrent AF remains an important knowledge gap. In this translational research proposal, we aim to fill this knowledge gap by studying the effect of Dapagliflozin on AF burden. AF burden will be defined as the percent of time spent in AF over a 2-week period, assessed by noninvasive continuous heart rhythm monitoring at baseline and at 3 months, quality of life (QOL) and validated echocardiographic indices of atrial myopathy. This knowledge will enable us to study the therapeutic potential of SGLT2i as a novel adjunct treatment for patients with DM and AF. Patients with paroxysmal AF (AF that terminates spontaneously or with intervention within seven days of onset) and DM will be enrolled. Subjects will be randomized to Dapagliflozin or placebo. Continuous heart rhythm monitoring patch for AF burden, measure QOL with the help of AF Effect on Quality-of-life survey and perform an echocardiogram with measurement of left atrial volume index, left atrial strain and atrial tissue dopplers. All measurements will be performed at baseline and at study completion. Our central hypothesis is that SGLT2i will lead to reduced AF burden that will translate into improvement in QOL, and the underlying mechanism is improvement in atrial myopathy.

Official Title
-----------------
Dapagliflozin in Patients With Atrial Fibrillation

Conditions
-----------------
Diabetes Mellitus, Atrial Fibrillation

Intervention / Treatment
-----------------
* Drug: Dapagliflozin 10Mg Tab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with DM Paroxysmal AF Exclusion Criteria: Type 1 DM, Symptoms of hypotension or systolic blood pressure <90mmHg, Severe renal impairment with eGFR<30mL/minute/1.73m2, History of lower limb amputation, Hypersensitivity to Dapagliflozin, Currently taking any SGLT2i, Pregnancy, Currently taking anti-arrhythmic drugs Undergoing catheter ablation will be excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double blind, placebo-controlled trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Arm (Placebo)<br>Subjects will take 1 blinded tablet of placebo drug dosed once daily, per the randomization scheme. | Drug: Placebo<br>* Subjects will take 1 blinded capsule of placebo drug dosed once daily<br>|
| Active Comparator: Intervention Arm (Dapagliflozin)<br>A block randomization method will be use to randomize subjects to treatment with dapagliflozin 10 mg once daily. Subjects will take 1 blinded tablet of study drug (dapagliflozin) dosed once daily, per the randomization scheme | Drug: Dapagliflozin 10Mg Tab<br>* Subjects will take 1 blinded tablet of study drug (dapagliflozin 10 mg) dosed once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of Dapagliflozin on change in burden of atrial fibrillation | To determine the effect of Dapagliflozin on change in AF burden in patients with AF and DM. AF burden will be defined as the percent of time spent in AF over a 2-week period, assessed by noninvasive continuous heart rhythm monitoring at baseline and at 3 months. The AF burden between Dapagliflozin vs Placebo will be compared. | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Dapagliflozin on change in AF Effect on Quality of Life Survey | To determine the effect of Dapagliflozin on change in quality of life in patients with AF and DM. AF Effect on Quality of Life Survey will be used to compare QOL between Dapagliflozin vs Placebo. | Baseline and 3 months |