Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation
Brief summary
This is a multicenter trial to evaluate the impact of treatment with dapagliflozin versus placebo following catheter ablation of atrial fibrillation (AF) on the burden of AF during 6-12 months of follow-up. This prospective, randomized, multicenter, placebo-controlled trial aims to enroll 25 subjects with AF (paroxysmal or persistent) who are scheduled to undergo catheter ablation of patients.
Detailed description
This is a multicenter trial to evaluate the impact of treatment with dapagliflozin versus placebo following catheter ablation of AF on the burden of AF during 6-12 months of follow-up. This prospective, randomized, multicenter, placebo-controlled trial aims to enroll 25 subjects with AF (paroxysmal or persistent) who are scheduled to undergo catheter ablation of patients. All enrolled subjects will be required to have a cardiac implantable electronic device (CIED) capable of assessing the burden of AF. Following catheter ablation for AF and functional CIED subjects will be randomized to treatment with dapagliflozin 10 mg once daily versus placebo. The primary endpoint for the trial will be AF burden assessed at 6-12 months following catheter ablation of AF. The Investigational Drug Services at the University of Rochester will be in charge of dispensing all study related drugs to subject.
Interventions
DRUGdapagliflozin
Subjects will take 1 blinded tablet of study drug (dapagliflozin 10 mg) dosed once daily, for 12 months.
DRUGPlacebo
Subjects will take 1 blinded capsule of placebo drug dosed once daily
Sponsors
AstraZeneca
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eligible for treatment with dapagliflozin per current FDA-approved indications, including: 1) heart failure (NYHA class II-IV) with reduced left ventricular ejection fraction (\<50%), or 2) type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors, or 3) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, 4) adults with chronic kidney disease at risk of progression as defined by the National Kidney Foundation as estimated GFR \<60 ml/minute/1.73 m2. * Scheduled to undergo ablation of symptomatic paroxysmal or persistent AF prior to date of randomization per current guideline indications. * A glycated hemoglobin level \< 10.5% during the past 6 calendar months prior to consent only in patients with type 2 diabetes mellitus * Age \> 18 years * Existing functional CIED or planned to undergo CIED implant as SOC before or within 24 hours following the AF ablation procedure and prior to randomization date.
Exclusion criteria
* Type 1 diabetes mellitus * History of diabetic keto-acidosis * Child Pugh Class C liver disease * Last measured estimated GFR \< 25 ml/minute/1.73 m2 * Pregnancy, plan to become pregnant \<1 year after consent or breast feeding * Current therapy with an SGLT2 inhibitor * Hypersensitivity to dapagliflozin * On heart transplant list or likely to undergo heart transplant * Unwilling or unable to cooperate with the protocol * Participation in other clinical trials (observational registries are allowed with approval). * Unwilling to sign the consent for participation * Life expectancy \<1 year after consent date for any medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage of Time Spent in Atrial Fibrillation | 12 months | For the primary endpoint of AF burden, defined as percentage of time spent in AF (i.e. amount of time spent in AF divided by the total amount of time a patient was monitored), the student's t-test will be used to statistically compare the placebo group vs. the active treatment group. This approach is subject to an examination of the distribution of the percent time in AF. AF data will be collected using a cardiac implantable electronic device (CIED). AF burden assessed at 6-12 months following catheter ablation of AF, defined as percentage of time spent in AF (i.e. amount of time spent in AF divided by the total amount of time a subject was monitored). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Health Care Utilization | 6-12 months | Rate of health care utilization (recurrent hospitalizations, unplanned office visits, need for emergency room visits) |
| Percentage of Participants Hospitalized for Heart Failure Post Catheter Ablation of AF | 6-12 months | — |
| Mean Quality of Life Score Using the QualiTy-of-life (AFEQT) Questionnaire | Final visit, approximately 12 months | The AFEQT questionnaire is an AF-specific health-related quality of life questionnaire designed to be used in clinical research. The responses on the AFEQT are scored on a Likert scale, 1 = Not at all… to 7 = Extremely. Scores range from 0 to 100. A score of 0 corresponds to complete disability and a score of 100 corresponds to no disability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Management Arm (Dapagliflozin) 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, for 12 months. Each subject will be dispensed 35 blinded doses per month, during each month of participation in the trial. Quarterly pill counts will be performed to track compliance.
dapagliflozin: Subjects will take 1 blinded tablet of study drug (dapagliflozin 10 mg) dosed once daily, for 12 months. | 12 |
| Control Arm (Placebo) Subjects will take 1 blinded tablet of placebo drug dosed once daily, per the randomization scheme, for 12 months. Each subject will be dispensed 35 blinded doses per month, during each month of participation in the trial. Quarterly pill counts will be performed to track compliance.
Placebo: Subjects will take 1 blinded capsule of placebo drug dosed once daily | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | Intervention Management Arm (Dapagliflozin) | Total | Control Arm (Placebo) |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 12 | 64 years STANDARD_DEVIATION 11 | 67 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 24 Participants | 13 Participants |
| Region of Enrollment United States | 12 participants | 25 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 6 / 12 | 5 / 13 |
| serious Total, serious adverse events | 1 / 12 | 1 / 13 |
Outcome results
Primary
Mean Percentage of Time Spent in Atrial Fibrillation
For the primary endpoint of AF burden, defined as percentage of time spent in AF (i.e. amount of time spent in AF divided by the total amount of time a patient was monitored), the student's t-test will be used to statistically compare the placebo group vs. the active treatment group. This approach is subject to an examination of the distribution of the percent time in AF. AF data will be collected using a cardiac implantable electronic device (CIED). AF burden assessed at 6-12 months following catheter ablation of AF, defined as percentage of time spent in AF (i.e. amount of time spent in AF divided by the total amount of time a subject was monitored).
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Management Arm (Dapagliflozin) | Mean Percentage of Time Spent in Atrial Fibrillation | 2.74 percentage of time | Standard Deviation 6.31 |
| Control Arm (Placebo) | Mean Percentage of Time Spent in Atrial Fibrillation | 5.85 percentage of time | Standard Deviation 12.85 |
Secondary
Mean Quality of Life Score Using the QualiTy-of-life (AFEQT) Questionnaire
The AFEQT questionnaire is an AF-specific health-related quality of life questionnaire designed to be used in clinical research. The responses on the AFEQT are scored on a Likert scale, 1 = Not at all… to 7 = Extremely. Scores range from 0 to 100. A score of 0 corresponds to complete disability and a score of 100 corresponds to no disability.
Time frame: Final visit, approximately 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Management Arm (Dapagliflozin) | Mean Quality of Life Score Using the QualiTy-of-life (AFEQT) Questionnaire | 20.7 score on a scale | Standard Deviation 8.8 |
| Control Arm (Placebo) | Mean Quality of Life Score Using the QualiTy-of-life (AFEQT) Questionnaire | 15.4 score on a scale | Standard Deviation 26.8 |
Secondary
Percentage of Participants Hospitalized for Heart Failure Post Catheter Ablation of AF
Time frame: 6-12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Management Arm (Dapagliflozin) | Percentage of Participants Hospitalized for Heart Failure Post Catheter Ablation of AF | 0 percentage of participants |
| Control Arm (Placebo) | Percentage of Participants Hospitalized for Heart Failure Post Catheter Ablation of AF | 0 percentage of participants |
Secondary
Rate of Health Care Utilization
Rate of health care utilization (recurrent hospitalizations, unplanned office visits, need for emergency room visits)
Time frame: 6-12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Management Arm (Dapagliflozin) | Rate of Health Care Utilization | 132 events |
| Control Arm (Placebo) | Rate of Health Care Utilization | 104 events |