Clinical trial NCT04570865: Dapagliflozin And Pulmonary Artery Hemodynamics in Heart Failure With Reduced Ejection Fraction Patients With CardioMEMS®
Official title: Dapagliflozin And Pulmonary Artery Hemodynamics in Heart Failure With Reduced Ejection Fraction Patients With CardioMEMS®
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure, Systolic
Lead sponsor: Scripps Health
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The focus of this study is to investigate the use of Dapagliflozin in HFrEF (NYHA II-IV) patients with or without diabetes who have CardioMEMS® implanted to assess the impact on pulmonary artery pressure measurements after 12 weeks of therapy.
Primary purpose: TREATMENT

Brief summary: The focus of this study is to investigate the use of Dapagliflozin in HFrEF (NYHA II-IV) patients with or without diabetes who have CardioMEMS® implanted to assess the impact on pulmonary artery pressure measurements after 12 weeks of therapy.

Detailed description: Prior studies have demonstrated an association between the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors for diabetic patients and reductions in composite primary outcomes of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke, as well as reductions in heart failure among patients with diabetes. The 2019 DAPA-HF trial studied whether the addition of the SCLT-2 inhibitor dapagliglozin could benefit patients with heart failure with reduced ejection fraction (HFrEF), either with or without diabetes. Results indicated that that SGLT-2 inhibitors resulted in 4.9% absolute reduction in the cardiovascular death or worsening heart failure and a 2.3% absolute reduction in all-cause mortality in patients with and without diabetes. Dapagliflozin is FDA approved to reduce the risk of cardiovascular death or hospitalization in patients with HFrEF with or without Type 2 diabtes. The mechanisms of cardiovascular benefit remain unclear, however it is likely to be driven by a reduction in heart failure death given that rates of myocardial infarction were similar between treatment arms.

The CardioMEMS® system is an implantable device that can measure pulmonary artery systolic, diastolic and mean pressure on a daily basis. It has been shown convincingly that monitoring the MEMS device results in reduced pulmonary pressures and in turn a reduction in heart failure hospitalizations.

The focus of this study is to investigate the use of Dapagliflozin in HFrEF (NYHA II-IV) patients with or without diabetes who have CardioMEMS® implanted to assess the impact on pulmonary artery pressure measurements after 12 weeks of therapy.

Eligibility criteria: Inclusion Criteria

1. Diagnosis of HFrEF and existing CardioMEMs in place
2. Patients who have historically been compliant with CardioMEMS followup
3. Ejection fraction \< or = to 40%
4. New York Heart Association (NYHA) class II-IV heart failure
5. Able to read and write in English Exclusion Criteria

1. creatinine clearance less than or equal to 45 2. History of renal transplant 3. systolic blood pressure less than 85 on time of initiation of drug 4. intolerance/allergy to farxiga 5. pregnant patients or those who are planning to become pregnant during the study period 6. unable to read and write in English 7. acutely hospitalized patients or those who were hospitalized in the past 30 days 8. history of noncompliance with CardioMEMS followup 9. History of frequent mycotic urinary tract infections 10. History of organ transplantation

Primary outcomes:
measure: Effect of Dapagliflozin on pulmonary diastolic pressure from baseline to 12 weeks of therapy Secondary End Points
timeFrame: 12 weeka
measure: Compare the change in PA pressures, systolic and mean, from baseline to 12 weeks.
timeFrame: 12 weeks
Secondary outcomes:
measure: Describe the change in NT-ProBNP from baseline to 12 weeks
timeFrame: 12 weeks
Other outcomes:
measure: Compare total diuretic dose from baseline to 12 weeks.
timeFrame: 12 weeks
measure: Determine the change in 6 min walk distance from baseline to 12 weeks
timeFrame: 12 weeks
measure: Compare the change in KCCQ from baseline to 12 weeks.
timeFrame: 12 weeks
measure: Change in renal function estimated GFR from baseline to 12 weeks
timeFrame: 12 weeks
measure: Change in weight baseline to 12 weeks
timeFrame: 12 weeks
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
Study officials:
References:
citation: 1. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657. doi:10.1056/NEJMoa1611925 2. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720 3. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. doi:10.1056/NEJMoa1812389 4. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303 5. Abraham WT, Adamson PB, Bourge RC, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: A randomised controlled trial. Lancet. 2011;377(9766):658-666. doi:10.1016/S0140-6736(11)60101-3