Clinical trial NCT03611153: Myeloperoxidase (MPO) Inhibitor A_Zeneca for Heart Failure With Preserved Ejection Fraction (HFpEF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Keywords: Heart Failure
Ejection Fraction
Preserved
Myeloperoxidase Inhibitor
Exercise
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2018-08-02
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single Administration of study drug
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: Baseline, approximately 30 minutes after study drug administration
measure: Exercise Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: Baseline
Secondary outcomes:
measure: Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: Baseline, approximately 30 minutes after study drug administration
measure: Change in Exercise Central Pressures
timeFrame: Baseline, approximately 30 minutes after study drug administration
measure: Change in Resting Central Pressures
timeFrame: Baseline, approximately 30 minutes after study drug administration
measure: Change in Exercise Transmyocardial Lactate Ratio
timeFrame: Baseline, approximately 30 minutes after drug administration
measure: Change in Resting Transmyocardial Lactate Ratio
timeFrame: Baseline, approximately 30 minutes after drug administration
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Barry A Borlaug, M.D.
role: PRINCIPAL_INVESTIGATOR
References: