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

NCT04697485 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: STU00213243
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

HF - Heart Failure; Diabetes Mellitus

Keywords

HFpEF

Outcome Measures

Primary Outcomes (1)

• Change in NT-proBNP

  Change in NT-proBNP after 4 weeks of treatment

  4 weeks

Secondary Outcomes (3)

• Change in Systolic and Diastolic Blood pressure

  4 weeks

• Change in body weight

  4 weeks

• Compliance

  4 weeks

Study Arms (1)

Low-Dose, Triple Polydiuretic Therapy (LDTPT)

EXPERIMENTAL

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

Drug: Bumetanide 0.5 mg, dapaglifozin 5 mg, eplerenone 25 mg

Interventions

Bumetanide 0.5 mg, dapaglifozin 5 mg, eplerenone 25 mg DRUG

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

Low-Dose, Triple Polydiuretic Therapy (LDTPT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Heart Failure; Diabetes Mellitus

Interventions

Bumetanide; Eplerenone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Sadiya Khan, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: January 6, 2021
• Study Start: January 8, 2021
• Primary Completion: January 1, 2022
• Study Completion: March 30, 2022
• Last Updated: May 10, 2022

Record last verified: 2022-05

Locations

US (1)