Back to resultsMPO Inhibitor A_Zeneca for HFpEF
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD4831 Oral Myeloperoxidase Inhibitor
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Ejection Fraction, Preserved, Myeloperoxidase Inhibitor, Exercise
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD4831 Oral myeloperoxidase inhibitor
Placebo
Arm Description
Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.
Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization.
Outcomes
Primary Outcome Measures
Exercise Pulmonary capillary wedge pressure (PCWP)
Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg
Exercise Pulmonary capillary wedge pressure (PCWP)
Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg
Secondary Outcome Measures
Full Information
NCT ID
NCT03611153
First Posted
July 26, 2018
Last Updated
January 24, 2023
Sponsor
Mayo Clinic
Collaborators
National Center for Advancing Translational Sciences (NCATS)
1. Study Identification
Unique Protocol Identification Number
NCT03611153
Brief Title
MPO Inhibitor A_Zeneca for 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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
February 11, 2022 (Actual)
Study Completion Date
February 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Center for Advancing Translational Sciences (NCATS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart Failure, Ejection Fraction, Preserved, Myeloperoxidase Inhibitor, Exercise
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Single Administration of study drug
Masking
ParticipantInvestigator
Masking Description
Only research pharmacy staff will be aware of randomization scheme and all study personnel and subjects will remain blinded.
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD4831 Oral myeloperoxidase inhibitor
Arm Type
Experimental
Arm Description
Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization.
Intervention Type
Drug
Intervention Name(s)
AZD4831 Oral Myeloperoxidase Inhibitor
Other Intervention Name(s)
Oral MPO inhibitor AZD4831
Intervention Description
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
Intervention Name(s)
Placebo oral capsule
Intervention Description
A single administration dose of 30 mg placebo given orally following baseline, resting and exercise testing in patients during right heart catheterization.
Primary Outcome Measure Information:
Title
Exercise Pulmonary capillary wedge pressure (PCWP)
Description
Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg
Time Frame
Baseline
Title
Exercise Pulmonary capillary wedge pressure (PCWP)
Description
Exercise PCWP values at 20 Watt workload. Measured in mmHg. Normal values are 4-12 mmHg
Time Frame
30min
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barry A Borlaug, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
MPO Inhibitor A_Zeneca for HFpEF
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