NCT03611153

Myeloperoxidase (MPO) Inhibitor A_Zeneca for Heart Failure With Preserved Ejection Fraction (HFpEF)

Completed Phase 1, PHASE2 Results posted Last updated 8 January 2025

What this trial tests

Phase 1, PHASE2 trial testing AZD4831 Oral Myeloperoxidase Inhibitor in Heart Failure in 30 participants. Completed in 24 February 2022.

Timeline

1 July 2018

Primary endpoint
11 February 2022

24 February 2022

Quick facts

Lead sponsor	Mayo Clinic
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	30
Start date	1 July 2018
Primary completion	11 February 2022
Estimated completion	24 February 2022
Sites	1 location across United States

Drugs / interventions tested

• AZD4831 Oral Myeloperoxidase Inhibitor — full drug profile →
• Placebo oral capsule

Conditions studied

• Heart Failure — all drugs for Heart Failure →

Sponsor

Mayo Clinic

Who can join

30 and older, any sex, with Heart Failure. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP) Primary · 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.

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	-1	± 3
Placebo	-4	± 5

Exercise Pulmonary Capillary Wedge Pressure (PCWP) Primary · 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.

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	31	± 6
Placebo	32	± 7

Change in Resting Pulmonary Capillary Wedge Pressure (PCWP) Secondary · 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 while in resting state, measured in mmHg.

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	-2	± 3
Placebo	-2	± 2

Change in Exercise Central Pressures Secondary · Baseline, approximately 30 minutes after study drug administration

Exercise values after receiving study drug minus exercise values before study drug, obtained at 20 Watt workload, measured in mmHg.

Right atrial pressure

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	0	± 3
Placebo	0	± 2

Pulmonary artery systolic pressure

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	-2	± 5
Placebo	-4	± 5

Mean pulmonary artery pressure

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	-1	± 4
Placebo	-4	± 5

Change in Resting Central Pressures Secondary · Baseline, approximately 30 minutes after study drug administration

Resting values after receiving study drug minus resting values before study drug, measured in mmHg.

Right atrial pressure

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	0	± 2
Placebo	0	± 1

Pulmonary artery systolic pressure

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	-3	± 5
Placebo	-3	± 5

Mean pulmonary artery pressure

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	-1	± 3
Placebo	-2	± 3

Change in Exercise Transmyocardial Lactate Ratio Secondary · Baseline, approximately 30 minutes after drug administration

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.

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	0.05	± 0.17
Placebo	-0.01	± 0.15

Change in Resting Transmyocardial Lactate Ratio Secondary · Baseline, approximately 30 minutes after drug administration

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.

Group	Value	95% CI
AZD4831 Oral Myeloperoxidase Inhibitor	0.16	± 0.49
Placebo	0.10	± 0.23

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected on each participant from the start of the invasive testing procedure and study drug administration, through the follow-up visit, which was approximately 9-14 days later; for a total of approximately 15 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD4831 Oral Myeloperoxidase Inhibitor

Serious: 0/15 (0%)

Deaths: 0/15

Placebo

Serious: 1/15 (7%)

Deaths: 0/15

Serious adverse events (1 terms)

Reaction	System	AZD4831 Oral Myeloperoxida…	Placebo
Hospitalization for Heart Failure	Cardiac disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	AZD4831 Oral Myeloperoxida…	Placebo
Nausea	General disorders	—	—
Vomiting	General disorders	—	—
Diarrhea	General disorders	—	—
Lower extremity deep vein thrombosis	General disorders	—	—

Most-reported serious reactions: Hospitalization for Heart Failure.

Data from ClinicalTrials.gov NCT03611153 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inflammation in Human Heart Failure: Major Mediators and Therapeutic Targets.
   Reina-Couto M, Pereira-Terra P, Quelhas-Santos J, Silva-Pereira C, et al · · 2021 · cited 108× · PMID 34707513 · DOI 10.3389/fphys.2021.746494
2. The many roles of myeloperoxidase: From inflammation and immunity to biomarkers, drug metabolism and drug discovery.
   Siraki AG. · · 2021 · cited 87× · PMID 34455146 · DOI 10.1016/j.redox.2021.102109
3. Chronic low-grade inflammation in heart failure with preserved ejection fraction.
   Mesquita T, Lin YN, Ibrahim A. · · 2021 · cited 77× · PMID 34382743 · DOI 10.1111/acel.13453
4. Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction.
   Nelander K, Lagerstrom-Fermer M, Amilon C, Michaëlsson E, et al · · 2021 · cited 33× · PMID 32770730 · DOI 10.1111/cts.12859
5. Safety, tolerability, pharmacokinetics and effect on serum uric acid of the myeloperoxidase inhibitor AZD4831 in a randomized, placebo-controlled, phase I study in healthy volunteers.
   Gan LM, Lagerström-Fermér M, Ericsson H, Nelander K, et al · · 2019 · cited 33× · PMID 30618054 · DOI 10.1111/bcp.13855
6. Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction-Profibrotic and Proinflammatory Pathways and Genes.
   Ye B, Bradshaw AD, Abrahante JE, Dragon JA, et al · · 2023 · cited 20× · PMID 37582166 · DOI 10.1161/circheartfailure.123.010395
7. Biomarkers in Peripartum Cardiomyopathy-What We Know and What Is Still to Be Found.
   Kryczka KE, Demkow M, Dzielińska Z. · · 2024 · cited 16× · PMID 38254703 · DOI 10.3390/biom14010103
8. Pathological mechanisms and crosstalk among various cell death pathways in cardiac involvement of systemic lupus erythematosus.
   Wei J, Wang A, Li B, Li X, et al · · 2024 · cited 8× · PMID 39301029 · DOI 10.3389/fimmu.2024.1452678