PolyPreventHF: Polypill for Prevention of Cardiomyopathy

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06143566

Collaborator

(none)

Enrollment

Location

Arms

11.1

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will investigate the utility of a polypill-based strategy for patients with type 2 diabetes mellitus and high risk of heart failure (HF), as assessed via the WATCH-DM risk score. Polypill therapy will consist of empagliflozin 12.5 mg, losartan 50 or 100 mg, and finerenone 10 mg daily. The study duration is 3 months, and participants will be randomized to either polypill therapy or usual care. The primary outcome is change in peak VO2 and adherence to usual care. The investigators hypothesize that the use of a polypill is feasible and improves medication adherence and peak VO2 as compared to those receiving usual care.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes High Blood Pressure	Drug: Polypill	Phase 1/Phase 2

Detailed Description

Heart failure (HF) is a major cause of cardiovascular morbidity and mortality. One of the risk factors for HF is diabetes mellitus (DM). Altered glucose and lipid metabolism in DM leads to fibrosis and cardiac remodeling, ultimately causing ventricular dysfunction. While there is no consensus on the definition of "diabetic cardiomyopathy", broadly it can be defined as presence of pathological left ventricular hypertrophy, fibrosis and left ventricular diastolic/systolic dysfunction. A risk prediction score called "WATCH-DM" that includes clinical, laboratory and echocardiographic data has been developed to predict HF risk in those with type 2 DM. Every unit increase was associated with a 24% increase in relative risk of HF within 5 years. Drugs that decrease HF incidence could potentially be used in patients with Type 2 DM to alleviate HF burden. This many also improve medication adherence, which is poor for patients with polypharmacy. The rationale for the study is as follows:

Heart failure represents a major contributor to mortality, morbidity, and healthcare costs
Adherence to medications that prevent heart failure is low.
A polypill strategy is an innovative approach to heart failure prevention that also promotes adherence, especially in underserved population.

The investigators propose a single-center, open-label, pragmatic, randomized pilot study of 30 participants with T2DM and high risk of heart failure, as determined by a WATCH-DM risk score greater than or equal to 11. Duration of follow up will be 3 months. The target population is patients receiving care at UT Southwestern Medical Center or Parkland Health for Type 2 Diabetes Mellitus and high risk of heart failure. 15 participants will receive polypill and 15 will receive usual care.The polypill will contain empagliflozin 12.5 mg, losartan 50 or 100 mg, and finerenone 10 mg and is dosed once daily. Our primary outcome will be the change in peak VO2 during a cardiopulmonary exercise test from baseline to 3 months. Secondary outcomes will include adherence, which will be assessed by the Morisky Medication Adherence Score - 8 (MMAS-8), pill count at baseline, 1 month and 3 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Participants will be randomized in 1:1 fashion.Participants will be randomized in 1:1 fashion.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Polypill Strategy for Prevention of Cardiomyopathy Among Patients With Diabetes at Risk of Heart Failure

Anticipated Study Start Date :

Dec 29, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Polypill Participants will take a polypill containing finerenone 10 mg, empagliflozin 12.5 mg, and losartan (50 mg or 100 mg) daily.	Drug: Polypill A combination of finerenone 10 mg, empagliflozin 12.5 mg, and losartan 50 mg or 100 mg within a polycapsule. Other Names: (Finerenone, Empagliflozin, Losartan)
No Intervention: Usual Care Participants will continue to take normal medications for diabetes and high blood pressure.

Arm

Intervention/Treatment

Experimental: Polypill

Participants will take a polypill containing finerenone 10 mg, empagliflozin 12.5 mg, and losartan (50 mg or 100 mg) daily.

Drug: Polypill

A combination of finerenone 10 mg, empagliflozin 12.5 mg, and losartan 50 mg or 100 mg within a polycapsule.

Other Names:

(Finerenone, Empagliflozin, Losartan)

No Intervention: Usual Care

Participants will continue to take normal medications for diabetes and high blood pressure.

Outcome Measures

Primary Outcome Measures

Oxygen uptake during peak exercise (Peak VO2) [Baseline and 3-month (study end)]
The ability of a polypill to improve or prevent declines in exercise capacity as measured by changes in peak oxygen uptake at exercise will be assessed.

Secondary Outcome Measures

Urine albumin to creatinine ratio [Baseline and 3 months]
The ratio of urinary albumin to creatinine will be measured.

Other Outcome Measures

Medication Adherence [Baseline, 1 month, and 3 month.]
Assessed via the Morisky Medication Adherence Score - 8. The score ranges from 0 to 8, with 8 meaning highest adherence.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with Type 2 DM and urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300 and an estimated glomerular filtration rate (eGFR) of 25 to 90 ml per minute per 1.73 m2 of body-surface area (stage 2 to 4 CKD) with either a:
High risk of HF as defined by High Watch-DM score (≥11) or
Elevated natriuretic peptides or
Diastolic dysfunction or left ventricular hypertrophy on echocardiography