Dapagliflozin (DAPA) Effects in HFpEF

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether treatment with Dapagliflozin (DAPA) for 6 months will improve pulmonary capillary wedge pressure (PCWP) during exercise in heart failure/preserved ejection fraction (HFpEF) and improve cardiac metabolism.

Official Title
-----------------
Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction (CAMEO-DAPA): A Phase II, Prospective, Double-Blind Study

Conditions
-----------------
Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
-----------------
* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent prior to any study specific procedures. Male or female. Symptoms of dyspnea (NYHA II-III) with no non-cardiac or ischemia explanation. EF ≥ 50% + BMI ≥ 30 kg/m^2 Elevated pulmonary capillary wedge pressure (PCWP) during exercise (≥ 25 mmHg) ascertained at Visit 1. Patients that have consented to study procedures but do not meet this invasive criterion will be considered as screen failures and will not be randomized . Exclusion Criteria: Type I diabetes. Type II diabetes with poor control (HgbA1C ≥ 10%). Recent hospitalization (< 30 days) or revascularization (< 90 days). Primary cardiomyopathy (such as amyloid). Constrictive pericarditis. Dyspnea due to primary lung disease or myocardial ischemia in the opinion of the investigator. Severe anemia (hemoglobin < 9gm/dl. Significant left-sided valvular heart disease (> mild stenosis, > moderate regurgitation), Severe kidney disease (estimated glomerular filtration rate (GFR) < 30) or liver disease,

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin Group<br>Subjects with HFpEF will take the study drug dapagliflozin daily | Drug: Dapagliflozin<br>* 10 mg orally once a day<br>|
| Placebo Comparator: Placebo Group<br>Subjects with HFpEF will take a placebo daily | Drug: Placebo<br>* Taken orally once a day, the placebo looks identical to the study drug but it contains no active ingredient<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Capillary Wedge Pressure (PCWP) at Maximal Exercise | Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter during exercise. | Baseline, 24 weeks | 
| Pulmonary Capillary Wedge Pressure (PCWP) at Rest | Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter during rest. | Baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Change in body weight as measured in kilograms (kg) | Baseline, 24 weeks | 
| Change in Total Blood Volume | Total blood volume was assessed using a radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique with the BVA-100 Blood Volume Analyzer. Measured in millimeters (mL) | Baseline, 24 weeks | 
| Change in Plasma Volume | Plasma volume was assessed using a radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique with the BVA-100 Blood Volume Analyzer. Measured in millimeters (mL) | Baseline, 24 weeks | 
| Change in Right Atrial (RA) Pressure at Maximal Exercise | Right Atrial (RA) pressure is a measure of cardiac filling pressure, measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter during exercise. | Baseline, 24 weeks | 
| Change in Right Atrial (RA) Pressure at Rest | Right Atrial (RA) pressure is a measure of cardiac filling pressure, measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter during rest. | Baseline, 24 weeks | 
| Change in Mean Pulmonary Arterial Pressure (PA) at Maximal Exercise | Pulmonary Arterial (PA) pressure is a measure of cardiac filling pressure, measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter during exercise. | Baseline, 24 weeks | 
| Change in Mean Pulmonary Arterial Pressure (PA) at Rest | Pulmonary Arterial (PA) pressure is a measure of cardiac filling pressure, measured using a high-fidelity micromanometer advanced through the lumen of a fluid-filled catheter during rest. | Baseline, 24 weeks |