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

Primary Purpose

HF - Heart Failure, Diabetes Mellitus

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Bumetanide 0.5 mg, dapaglifozin 5 mg, eplerenone 25 mg

About this trial

This is an interventional treatment trial for HF - Heart Failure focused on measuring HFpEF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adults (≥18 years old)
English speaker
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.
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)
Type 2 diabetes mellitus, regardless of background insulin use

Exclusion Criteria:

Known contraindication to bumetanide, eplerenone, or dapagliflozin.
Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements at visit 1.
Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment.
Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment.
HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
Type 1 diabetes mellitus
Symptomatic bradycardia or second or third-degree heart block without a pacemaker.
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).
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).
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.
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.
Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to participate in the study.
Inability or unwillingness to provide written informed consent.
Involvement in the planning and/or conduct of the study.
Receiving current treatment with sulfonylureas.
Unable to complete study procedures.

Sites / Locations

Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Low-Dose, Triple Polydiuretic Therapy (LDTPT)

Arm Description

Polydiuretic therapy will consist of bumetanide 0.5 mg + eplerenone 25 mg + dapaglifozin 5 mg once daily for 4 weeks.

Outcomes

Primary Outcome Measures

Change in NT-proBNP

Change in NT-proBNP after 4 weeks of treatment

Secondary Outcome Measures

Change in Systolic and Diastolic Blood pressure

Change in blood pressure after 4 weeks of treatment

Change in body weight

Change in weight after 4 weeks of treatment

Compliance

Overall compliance with polydiuretic as assessed by pill count

Full Information

NCT ID

NCT04697485

First Posted

December 7, 2020

Last Updated

May 4, 2022

Sponsor

Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT04697485

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Enrollment and funding challenges

Study Start Date

January 8, 2021 (Actual)

Primary Completion Date

January 1, 2022 (Actual)

Study Completion Date

March 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief 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).

Detailed 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HF - Heart Failure, Diabetes Mellitus

Keywords

HFpEF

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Model Description

This will be a proof-of-concept, non-randomized, pilot study of patients with HFpEF and diabetes mellitus to receiving polydiuretic therapy (bumetanide 0.5 mg + eplerenone 25 mg + dapaglifozin 5 mg) on top of background therapy

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low-Dose, Triple Polydiuretic Therapy (LDTPT)

Arm Type

Experimental

Arm Description

Polydiuretic therapy will consist of bumetanide 0.5 mg + eplerenone 25 mg + dapaglifozin 5 mg once daily for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Bumetanide 0.5 mg, dapaglifozin 5 mg, eplerenone 25 mg

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in NT-proBNP

Description

Change in NT-proBNP after 4 weeks of treatment

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Change in Systolic and Diastolic Blood pressure

Description

Change in blood pressure after 4 weeks of treatment

Time Frame

4 weeks

Title

Change in body weight

Description

Change in weight after 4 weeks of treatment

Time Frame

4 weeks

Title

Compliance

Description

Overall compliance with polydiuretic as assessed by pill count

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adults (≥18 years old) English speaker 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. 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) Type 2 diabetes mellitus, regardless of background insulin use Exclusion Criteria: Known contraindication to bumetanide, eplerenone, or dapagliflozin. Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements at visit 1. Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment. Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease. Type 1 diabetes mellitus Symptomatic bradycardia or second or third-degree heart block without a pacemaker. 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). 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). 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. 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. Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to participate in the study. Inability or unwillingness to provide written informed consent. Involvement in the planning and/or conduct of the study. Receiving current treatment with sulfonylureas. Unable to complete study procedures.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sadiya Khan, MD

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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