MPO Inhibitor A_Zeneca for HFpEF

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03611153
• Other study ID #: 17-002907
• Secondary ID: UL1TR000135
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 1, 2018
• Est. completion date: February 24, 2022

Study information

• Verified date: January 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 24, 2022
• Est. primary completion date: February 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exercise Pulmonary capillary wedge pressure (PCWP)	Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg	Baseline
Primary	Exercise Pulmonary capillary wedge pressure (PCWP)	Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg	30min

External Links

•   Mayo Clinic Clinical Trials