Myeloperoxidase (MPO) Inhibitor A_Zeneca for Heart Failure With Preserved Ejection Fraction (HFpEF)

Mayo Clinic30 enrolled

Overview

Researchers are studying the effect of a single dose of oral myeloperoxidase on heart failure versus placebo.

Enroll subjects with a normal ejection fraction referred to the catheterization laboratory for evaluation of breathlessness or shortness of breath. Perform safety lab sampling, echocardiography, arterial tonometry for pulse wave analysis, and assessment of endothelial function prior to administration of study drug. During the catheterization researchers will perform blood draws, assess baseline exercise capacity at rest and during exercise. Researchers will also do an echocardiogram to take measurements of the heart. Subjects will be randomized to one of two groups, Oral Myeloperoxidase Inhibitor or placebo group. Study drug or placebo will be administered followed by a repeat of the baseline catheterization assessments. At the conclusion of the second exercise test the subject will be moved to a room and monitored overnight for safety. Repeat blood draws, echocardiogram, endothelial function test, and heart monitoring will be completed. The subject will be asked to follow up with the researchers between 9-14 days after the study drug dosage. The subjects history and blood work will be completed at that visit.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Heart Failure

Interventions

AZD4831 Oral Myeloperoxidase InhibitorDRUG

A single administration dose of 30 mg oral MPO inhibitor given orally following baseline, resting and exercise testing in patients during right heart catheterization.

Placebo oral capsuleDRUG

A single administration dose of 30 mg placebo given orally following baseline, resting and exercise testing in patients during right heart catheterization.

Eligibility

Sex: ALLMin age: 30 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Males and females of non-childbearing potential 2. Age ≥ 30 years 3. Symptoms of dyspnea (II-IV) at the time of screening 4. Ejection Fraction (EF) ≥ 50% as determined on imaging study within 12 months of enrollment 5. Catheterization documented elevated filling pressures at rest (PCWP ≥15) or with exercise (PCWP ≥25) Exclusion Criteria: 1. Use of nitrates, phosphodiesterase 5 inhibitors or other NO-providing therapy in the past 24 hours of screening 2. Significant valvular disease (\>moderate left-sided regurgitation, \>mild stenosis) 3. Requirement of intravenous heparin at the start of case 4. Severe pulmonary parenchymal disease 5. Acute coronary syndrome or coronary disease requiring revascularization in the judgement of investigators 6. Resting systolic blood pressure \< 100 mmHg 7. Constrictive pericarditis 8. Infiltrative, restrictive, or hypertrophic obstructive cardiomyopathies 9. Previous anaphylaxis to any drug 10. Pregnancy or breastfeeding mothers 11. High Output heart failure 12. Active thyroid disease 13. Treatment with a new chemical entity (defined as a compound which has not been approved for marketing) within the preceding 3 months 14. Patients with any prior allergy to propylthiouracil

Locations (1)

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)

Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.

Time frame: Baseline, approximately 30 minutes after study drug administration

Exercise Pulmonary Capillary Wedge Pressure (PCWP)

Time frame: Baseline

Secondary Outcomes

Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)

Time frame: Baseline, approximately 30 minutes after study drug administration

Change in Exercise Central Pressures

Exercise values after receiving study drug minus exercise values before study drug, obtained at 20 Watt workload, measured in mmHg.

Time frame: Baseline, approximately 30 minutes after study drug administration

Change in Resting Central Pressures

Resting values after receiving study drug minus resting values before study drug, measured in mmHg.

Time frame: Baseline, approximately 30 minutes after study drug administration

Data from ClinicalTrials.gov

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