MPO Inhibitor A_Zeneca for HFpEF

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

Detailed Description
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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.

Official Title
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Hemodynamic Effects of a Novel Myeloperoxidase Inhibitor With Exercise in Heart Failure With Preserved Ejection Fraction - A Randomized, Double-Blind, Placebo Controlled Proof of Principle Study

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: AZD4831 Oral Myeloperoxidase Inhibitor
* Drug: Placebo oral capsule


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

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single Administration of study drug
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD4831 Oral myeloperoxidase inhibitor<br>Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization. | Drug: AZD4831 Oral Myeloperoxidase Inhibitor<br>* A single administration dose of 30 mg oral MPO inhibitor given orally following baseline, resting and exercise testing in patients during right heart catheterization.<br>* Other names: Oral MPO inhibitor AZD4831;|
| Placebo Comparator: Placebo<br>Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization. | Drug: Placebo oral capsule<br>* A single administration dose of 30 mg placebo given orally following baseline, resting and exercise testing in patients during right heart catheterization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Pulmonary capillary wedge pressure (PCWP) | Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg | Baseline | 
| Exercise Pulmonary capillary wedge pressure (PCWP) | Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg | 30min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Ejection Fraction, Preserved, Myeloperoxidase Inhibitor, Exercise