MPO Inhibitor A_Zeneca for HFpEF

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

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

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: AZD4831 Oral Myeloperoxidase Inhibitor

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization.	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.
Experimental: AZD4831 Oral myeloperoxidase inhibitor; Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.	Drug: 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.; Other Names: Oral MPO inhibitor AZD4831

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Barry A Borlaug, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): February 11, 2022
• Study Completion (Actual): February 24, 2022

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Exercise; Ejection Fraction; Preserved; Myeloperoxidase Inhibitor
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 17-002907; UL1TR000135 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No