Heart FailurePhase 1/2NCT03611153
Myeloperoxidase (MPO) Inhibitor A_Zeneca for Heart Failure With Preserved Ejection Fraction (HFpEF)
A Phase 1/2 study testing AZD4831 Oral Myeloperoxidase Inhibitor in people with Heart Failure, run by Mayo Clinic at 1 site in United States.
Trial summary
Researchers are studying the effect of a single dose of oral myeloperoxidase on heart failure versus placebo. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- AZD4831 Oral Myeloperoxidase Inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2018to 24 Feb 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females of non-childbearing potential
- Age ≥ 30 years
- Symptoms of dyspnea (II-IV) at the time of screening
- Ejection Fraction (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)
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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
Researchers are studying the effect of a single dose of oral myeloperoxidase on heart failure versus placebo.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- AZD4831 Oral Myeloperoxidase Inhibitor, Placebo oral capsule
- Keywords
- Heart Failure, Ejection Fraction, Preserved, Myeloperoxidase Inhibitor, Exercise
- Medical subject headings
- Heart Failure, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4831 Oral Myeloperoxidase InhibitorDrug
Also called Oral MPO inhibitor AZD4831
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 capsuleDrug
A single administration dose of 30 mg placebo given orally following baseline, resting and exercise testing in patients during right heart catheterization.
| Study group | Role | What they receive |
|---|---|---|
| AZD4831 Oral myeloperoxidase inhibitor | Experimental | Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization. Receives: Drug: AZD4831 Oral Myeloperoxidase Inhibitor |
| Placebo | Placebo comparator | Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.
Measured: Baseline, approximately 30 minutes after study drug administration
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.
Measured: Baseline
Secondary outcomes (5)
Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch while in resting state, measured in mmHg.
Measured: Baseline, approximately 30 minutes after study drug administration
Change in Exercise Central Pressures
Exercise values after receiving study drug minus exercise values before study drug, obtained at 20 Watt workload, measured in mmHg.
Measured: Baseline, approximately 30 minutes after study drug administration
Change in Resting Central Pressures
Resting values after receiving study drug minus resting values before study drug, measured in mmHg.
Measured: Baseline, approximately 30 minutes after study drug administration
Change in Exercise Transmyocardial Lactate Ratio
Obtained at 20 Watt workload, determined by the lactate extraction ratio, which is calculated as lactate arterial minus lactate coronary sinus (CS) divided by lactate arterial. Negative values are indicative of myocardial ischemia.
Measured: Baseline, approximately 30 minutes after drug administration
Change in Resting Transmyocardial Lactate Ratio
Obtained during resting state, determined by the lactate extraction ratio, which is calculated as lactate arterial minus lactate coronary sinus (CS) divided by lactate arterial. Negative values are indicative of myocardial ischemia.
Measured: Baseline, approximately 30 minutes after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study start1 Jul 2018
- Primary completion11 Feb 2022
- Study completion24 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single Administration of study drug
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Barry Borlaug, Mayo Clinic
- Investigators
- Barry A Borlaug, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03611153
- Sponsor's protocol ID
- 17-002907
- Other IDs
- UL1TR000135
- Status last verified
- Dec 2024
- First submitted
- 26 Jul 2018
- Last updated
- 8 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03611153
- Acronym / sponsor ID
- 17-002907
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Ejection Fraction, Preserved, Myeloperoxidase Inhibitor, Exercise
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 11 Feb 2022 (actual)
- Study completion
- 24 Feb 2022 (actual)
- First posted
- 2 Aug 2018 (actual)
- Results
- Posted 8 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Single Administration of study drug
| Arm | Type | Receives |
|---|---|---|
| AZD4831 Oral myeloperoxidase inhibitor | Experimental | Drug: AZD4831 Oral Myeloperoxidase InhibitorPatient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization. |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePatient may take 30 mg of placebo oral capsule following baseline right heart catheterization. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males and females of non-childbearing potential
- Age ≥ 30 years
- Symptoms of dyspnea (II-IV) at the time of screening
- Ejection Fraction (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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4831 Oral Myeloperoxidase InhibitorAlso: Oral MPO inhibitor AZD4831A single administration dose of 30 mg oral MPO inhibitor given orally following baseline, resting and exercise testing in patients during right heart catheterization. | Drug | AZD4831 Oral myeloperoxidase inhibitor |
| Placebo oral capsuleA single administration dose of 30 mg placebo given orally following baseline, resting and exercise testing in patients during right heart catheterization. | Drug | Placebo |
Primary outcome
Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Time frame: Baseline, approximately 30 minutes after study drug administration
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
Time frame: Baseline
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.
5 secondary outcomes
Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)
Time frame: Baseline, approximately 30 minutes after study drug administration
Change in Exercise Central Pressures
Time frame: Baseline, approximately 30 minutes after study drug administration
Change in Resting Central Pressures
Time frame: Baseline, approximately 30 minutes after study drug administration
Change in Exercise Transmyocardial Lactate Ratio
Time frame: Baseline, approximately 30 minutes after drug administration
Change in Resting Transmyocardial Lactate Ratio
Time frame: Baseline, approximately 30 minutes after drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barry A Borlaug, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD4831 Oral Myeloperoxidase Inhibitor in people with Heart Failure, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP) (time frame: Baseline, approximately 30 minutes after study drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.