Polydiuretic Therapy for Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus

Diabetes Mellitus Clinical Trial

Official title:

Polydiuretic Therapy for Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus: A Pilot Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04697485
• Other study ID #: STU00213243
• Status: Withdrawn
• Phase: Phase 4
• Start date: January 8, 2021
• Est. completion date: March 30, 2022

Study information

• Verified date: May 2022
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-center, non-randomzied pilot study investigating a combination of targeted therapies as possible treatment for heart failure with preserved ejection fraction (HFpEF).

The study interviention is a Low-Dose, Triple Polydiuretic Therapy (LDTPT, or polydiuretic) including loop diuretic (bumetanide), mineralocorticoid receptor antagonist (eplerenone), and Sodium-glucose co-transporter 2 inhibitors (SGLT2i) therapy (dapaglifozin).

Description:

Patients with HFpEF and diabetes mellitus will receive polydiuretic therapy consisting of bumetanide 0.5 mg + eplerenone 25 mg + dapaglifozin 5 mg on top of background therapy. These medicines are currently FDA approved and recommended by clinical practice guidelines for the treatment of HFpEF (bumetanide, eplerenone) and diabetes mellitus (dapaglifozin).

This study is designed to evaluate if combination pharmacotherapies with synergistic or additive diuretic properties can improve adherence, treatment efficacy, and effectiveness with fewer side effects

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 30, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults (=18 years old)

2. English speaker

3. Established diagnosis of NYHA Class II or III heart failure with preserved ejection fraction, which has been present for at least 2 months

a. NB: Patients in which additional pharmacological or device therapy is contemplated, or should be considered, must not be enrolled until therapy has been optimized and is stable for =1 month.

4. NT-proBNP >600 pg/ml (or if hospitalized for heart failure within the previous 12 months, NT-proBNP =400 pg/ml) at enrolment (Visit 1)

a. If concomitant atrial fibrillation at Visit 1, NT-proBNP must be =900 pg/ml (irrespective of history of heart failure hospitalization)

5. Type 2 diabetes mellitus, regardless of background insulin use

Exclusion Criteria:

1. Known contraindication to bumetanide, eplerenone, or dapagliflozin.

2. Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements at visit 1.

3. Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment.

4. Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment.

5. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.

6. Type 1 diabetes mellitus

7. Symptomatic bradycardia or second or third-degree heart block without a pacemaker.

8. Evidence of secondary cause of hypertension e.g., renal artery stenosis; significant renal impairment (eGFR <50 ml/min/1.73 m2), raised serum potassium (above lab normal limit of 5.5 mEq/L).

9. Women who are pregnant, breast feeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods).

10. Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment.

11. Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.

12. Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to participate in the study.

13. Inability or unwillingness to provide written informed consent.

14. Involvement in the planning and/or conduct of the study.

15. Receiving current treatment with sulfonylureas.

16. Unable to complete study procedures.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Heart Failure
• HF - Heart Failure

Intervention

Drug:
• Bumetanide 0.5 mg, dapaglifozin 5 mg, eplerenone 25 mg
Low-Dose, Triple Polydiuretic Therapy (LDTPT) Treatment consists of: Loop diuretic (bumetanide 0.5 mg) Mineralocorticoid receptor antagonist (eplerenone 25 mg) Sodium-glucose co-transporter 2 inhibitor (SGLT2i): Farxiga® (dapagliflozin) 5 mg

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in NT-proBNP	Change in NT-proBNP after 4 weeks of treatment	4 weeks
Secondary	Change in Systolic and Diastolic Blood pressure	Change in blood pressure after 4 weeks of treatment	4 weeks
Secondary	Change in body weight	Change in weight after 4 weeks of treatment	4 weeks
Secondary	Compliance	Overall compliance with polydiuretic as assessed by pill count	4 weeks