Dapagliflozin And Pulmonary Artery Hemodynamics in Heart Failure With Reduced Ejection Fraction Patients With CardioMEMS® (DAPA-MEMS)

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure, Systolic
• Intervention / Treatment: Drug: Dapagliflozin; Device: CardioMEMS

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Dapagliglozin; 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.

Drug: Dapagliflozin; 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.; Device: CardioMEMS; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Dapagliflozin on pulmonary diastolic pressure from baseline to 12 weeks of therapy Secondary End Points	PA diastolic pressure change	12 weeka
Compare the change in PA pressures, systolic and mean, from baseline to 12 weeks.	PA pressure changes	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the change in NT-ProBNP from baseline to 12 weeks	NTproBNP change	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare total diuretic dose from baseline to 12 weeks.	diuretic dose	12 weeks
Determine the change in 6 min walk distance from baseline to 12 weeks	6 MWT	12 weeks
Compare the change in KCCQ from baseline to 12 weeks.	KCCQ	12 weeks
Change in renal function estimated GFR from baseline to 12 weeks	renal function	12 weeks
Change in weight baseline to 12 weeks	weight	12 weeks

Collaborators and Investigators

• Sponsor: Scripps Health

Publications and helpful links

General Publications

• 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

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2020
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): February 1, 2022

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (ACTUAL): September 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: DAPA-MEMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes