Polypill for Prevention of Cardiomyopathy

Phase 1

Recruiting

• Conditions: Type 2 Diabetes; High Blood Pressure
• Interventions: Drug: Polypill; Drug: Combined prescription of the individual medications

• Registration Number: NCT06143566
• Lead Sponsor: University of Texas Southwestern Medical Center

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 25, 50 or 100 mg, and finerenone 10 mg daily. The study duration is 6 months, and participants will be randomized to either polypill therapy or simultaneous prescription of the individual drugs. 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.

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 study of 200 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 6 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. 100 participants will receive polypill and 100 will receive simultaneous individual prescriptions.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 6 months. Secondary outcomes will include change in urine albumin creatine ratio, adherence, which will be assessed by the Morisky Medication Adherence Score - 8 (MMAS-8), pill count at baseline, 1 month and 3 months, and 6 months.

Study Timeline

• Study First Submitted: 2023-11-16
• Study First Submitted QC: 2023-11-16
• Study First Posted: 2023-11-22
• Study Start: 2024-03-11
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-12
• Last Update Posted: 2025-06-17
• Primary Completion: 2027-09-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Patients with Type 2 DM
• History of chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) of 25 to 90 per minute per 1.73 m2 of body-surface area (stage 2 to 4 CKD) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of less than 5000
• 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

Exclusion Criteria

• eGFR < 25
• Congestive heart failure
• Hyperkalemia > 5.0
• Contraindication to any component of polypill
• Pregnancy
• Creatinine >2.0mg/dL in men and >1.8mg/dL in women
• Inability to calculate WATCH-DM score
• Inability to undergo exercise testing

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Polypill	Polypill	Participants will take a polypill containing finerenone 10 mg, empagliflozin 12.5 mg, and losartan (25, 50 mg, or 100 mg) daily.
Combined prescription of the individual medications	Combined prescription of the individual medications	Participants will be initiated on an SGLT2i, ARB, or finerenone if they are not already on the medication class.

Primary Outcome Measures

Name	Time	Method
Oxygen uptake during peak exercise (Peak VO2)	Baseline, 3-month, and 6-month	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

Name	Time	Method
Urine albumin to creatinine ratio	Baseline, 3 month, and 6 month	The ratio of urinary albumin to creatinine will be measured.

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States