MPO Inhibitor A_Zeneca for HFpEF

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT03611153

Collaborator

(none)

Enrollment

Location

Arms

43.8

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Oral Myeloperoxidase Inhibitor Drug: Placebo oral capsule	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single Administration of study drugSingle Administration of study drug

Masking:

Double (Participant, Investigator)

Masking Description:

Only research pharmacy staff will be aware of randomization scheme and all study personnel and subjects will remain blinded.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 1, 2018

Actual Primary Completion Date :

Feb 11, 2022

Actual Study Completion Date :

Feb 24, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral myeloperoxidase inhibitor Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.	Drug: 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
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.

Arm

Intervention/Treatment

Experimental: Oral myeloperoxidase inhibitor

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

Drug: 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

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.

Outcome Measures

Primary Outcome Measures

Exercise Pulmonary capillary wedge pressure (PCWP) [Baseline]
Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg
Exercise Pulmonary capillary wedge pressure (PCWP) [30min]
Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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