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

Mayo Clinic

Status and phase: Completed; Phase 2; Phase 1

Conditions: Heart Failure

Treatments: Drug: AZD4831 Oral Myeloperoxidase Inhibitor; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03611153

17-002907

UL1TR000135 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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30 participants in 2 patient groups, including a placebo group

AZD4831 Oral myeloperoxidase inhibitor

Experimental group

Description:

Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.

Treatment:

Drug: AZD4831 Oral Myeloperoxidase Inhibitor

Placebo

Placebo Comparator group

Description:

Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization.

Treatment:

Drug: Placebo oral capsule