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

NCT ID: NCT03611153

Last Updated: 2025-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2022-02-24

Brief Summary

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

Detailed 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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

AZD4831 Oral myeloperoxidase inhibitor

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

Group Type: EXPERIMENTAL

AZD4831 Oral Myeloperoxidase Inhibitor

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

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

Interventions

AZD4831 Oral Myeloperoxidase Inhibitor

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

Intervention Type: DRUG

Placebo oral capsule

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

Intervention Type: DRUG

Other Intervention Names

Oral MPO inhibitor AZD4831

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Barry Borlaug

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barry A Borlaug, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UL1TR000135

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-002907

Identifier Type: -

Identifier Source: org_study_id