Heart Failure With Preserved Ejection FractionPhase 2/3ENDEAVORNCT04986202

Study to Evaluate the Efficacy and Safety of AZD4831 in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%

A Phase 2/3 study testing AZD4831 in people with Heart Failure With Preserved Ejection Fraction, run by AstraZeneca at 171 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is a randomised, double-blind, placebo-controlled, multi-center sequential phase 2b and Phase 3 study to evaluate the efficacy and safety of AZD4831 administered for up to 48 Weeks in participants with heart failure with left ventricular ejection fraction > 40%. Read more about this study

Who is it for?: Ages 40 to 85 years
Conditions the study is for: Heart Failure With Preserved Ejection Fraction
What is being tested?: AZD4831
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 711 participants
Where: 171 sitesin 18 countries
Study dates: 30 Jun 2021to 27 Mar 2024
Phase: Phase 2/3
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 40 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Part A
≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
Documented stable symptomatic HF (New York Heart Association Class II-IV) for at least 1 month at Screening (Visit 1) (transient HF in the setting of an MI does not qualify), with a medical history of typical symptoms of HF and receiving optimal therapy for HF as determined by the health-care physician.
LVEF > 40% at Screening (Visit 1). All participants will undergo a local echocardiogram at the Screening (Visit 1) with central reading to confirm the LVEF > 40% eligibility criteria before randomisation.
6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.
KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 3)

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NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤30 kg/m2.
NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2.
The ECG performed at Screening should be used for heart rhythm evaluation.
7.At least one of the following:
Structural heart disease, ie, LA enlargement and/or left ventricular hypertrophy at the echocardiogram performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34 mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or LVMI > 95 g/m2 in women and > 115 g/m2 in men.
Spectral tissue Doppler echocardiography - E/e' ratio (average of septal and lateral) ≥ 13 at rest at the echocardiogram performed at Screening (Visit 1).
Indirectly estimated elevation of PASP by TRmax velocity > 2.8 m/s (280 cm/s) (PASP > 35 mmHg) at the echocardiogram performed at Screening (Visit 1) OR directly measured pulmonary capillary wedge pressure > 15 mmHg at rest within the past 12 months or > 25 mmHg at exercise documented by right heart catheterisation within 12 months prior to Screening (Visit 1).
HF decompensation within 6 months before Randomisation (Visit 3), defined as hospitalisation for HF or IV diuretic treatment for HF during an urgent, unscheduled visit without hospitalisation.
8.Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
9.Male or female of non-childbearing potential.
Part B
Participant must be ≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
Documented diagnosis of symptomatic HF (NYHA class II-IV) at Screening (Visit 1), and a medical history of typical symptoms/signs of heart failure ≥ 6 weeks before Screening (Visit 1), and receiving optimal therapy for HF as determined by the health-care physician, with at least intermittent need for diuretic treatment.
LVEF >40% and evidence of structural heart disease (ie, left ventricular hypertrophy or
left atrial enlargement [defined by at least one of the following:LA enlargement and/or left ventricular hypertrophy at the echocardiogram
performed at Screening (Visit 1). Left atrial enlargement is defined by at least 1 of the following: LA width
(diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm, or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LAVI > 34
mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness ≥ 1.1 cm or
LVMI > 95 g/m2 in women and > 115 g/m2 in men.]) documented by the most recent echocardiogram, or cardiac
magnetic resonance imaging within the last 12 months prior to Screening (Visit 1). If no
echocardiogram is available, it can be performed at Screening (Visit 1).
6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 2). Difference in 6MWD between Screening and Randomisation must be < 50 meters
KCCQ-TSS ≤ 90 points at Screening (Visit 1) and Randomisation (Visit 2).
NT-proBNP ≥ 250 pg/mL (sinus rhythm) or ≥ 500 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI ≤ 30 kg/m2. NT-proBNP ≥ 200 pg/mL (sinus rhythm) or ≥ 400 pg/mL (atrial fibrillation/flutter) at Screening (Visit 1) for patients with BMI > 30 kg/m2. The ECG performed at Screening should be used for heart rhythm evaluation
Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
Male or female of non-childbearing potential.

Who cannot join

Part A
1 eGFR < 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).
2. Systolic blood pressure < 90 mmHg or ≥ 160 mmHg if not on treatment with ≥ 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments at Randomisation
3. Heart rate > 110 bpm or < 50 bpm at Randomisation
4. Life expectancy < 3 years due to other reasons than cardiovascular disease.
5. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).

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6. Presence of any disease or condition rather than HF constituting the main reason for limiting the ability to exercise/reduced exercise capacity.
7. Current decompensated HF and/or NT-proBNP > 5000 pg/mL at Screening (Visit 1)
8. Documented history of ejection fraction ≤ 40%.i.e. HF with recovered ejection fraction. Transient ejection fraction decrease e.g. in the setting of an MI does not apply
9. Any planned cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
10. Any cardiac event (eg, myocardial infarction, unstable angina), coronary revascularisation (percutaneous coronary intervention or coronary artery bypass grafting), ablation of atrial fibrillation/flutter, valve repair/replacement, implantation of a cardiac resynchronisation therapy device within 12 weeks prior to Screening (Visit 1) or between Screening and Randomisation. Patients who underwent a successful atrial fibrillation/flutter cardioversion, can be enrolled in the study after 4 weeks.
14. Hb < 110 g/L (male) and < 100 g/L (female) or iron-deficiency with/without anaemia requiring ongoing or planned IV iron treatment.
15. Participants with hyperthyroidism, uncontrolled hypothyroidism (including but not limited to TSH ≥10 mIU/mL), or any clinically significant thyroid disease as judged by the investigator.
18. ALT or AST ≥ 2 × ULN at Screening (Visit 1).
19. Pulmonary arterial hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening (Visit 1).
20. Any active infection requiring oral, intravenous or intramuscular treatment at Screening (Visit 1) and/or at Randomisation.
23 Any signs or confirmation of COVID-19 infection:
Suspected (as judged by PI) or confirmed COVID-19 within the last 2 weeks prior to Screening (Visit 1) or at Randomisation.
Hospitalisation for COVID-19 within the last 12 weeks prior to Screening (Visit 1).
24. Any concomitant medications known to be a potent CYP3A4 inducers or inhibitors, eg, itraconazole, rifampicin, clarithromycin, or propylthiouracil
29. Previous enrolment and randomisation in the present study. (Participants who where screened and screen failed and not randomised in Part A can be screened for possible entry to Part B).
All exclusion criteria in Part A are applicable to Part B with the following exceptions:
Exclusion Criteria specific for Part B only [criteria numeration for Part B]
4. Life expectancy < 2 years due to other reasons than cardiovascular disease.
11. HF due to any of the following: known infiltrative cardiomyopathy (eg, amyloid, sarcoid, lymphoma, endomyocardial fibrosis), active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), or uncorrected primary valvular disease.
18. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (ie, requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory support within 12 months prior to Screening [Visit 1]).

Trial locations and contacts

171 sites in 18 countries.

Country

City, postcode or hospital

171 sites in 18 countries

United States21 sites

Research Site
Alexander City, Alabama, 35010
Research Site
Baltimore, Maryland, 21229
Research Site
Buffalo, New York, 14215
Research Site
Chapel Hill, North Carolina, 27599
Research Site
Cleveland, Ohio, 44195
Research Site
Evanston, Illinois, 60208
Research Site
Hazel Crest, Illinois, 60429
Research Site
Knoxville, Tennessee, 37916
Research Site
Little Rock, Arkansas, 72205
Research Site
Miami, Florida, 33144
Research Site
Miami Beach, Florida, 33140
Research Site
New York, New York, 10019
Research Site
Norfolk, Virginia, 23510
Research Site
Ocala, Florida, 34471
Research Site
Philadelphia, Pennsylvania, 19107
Research Site
Pinehurst, North Carolina, 28374
Research Site
Rosedale, New York, 11422
Research Site
Sacramento, California, 95821
Research Site
Shreveport, Louisiana, 71105
Research Site
St Louis, Missouri, 63136
Research Site
Tullahoma, Tennessee, 37388

Other trials in United States

Japan20 sites

Research Site
Fukui-shi, 910-8526
Research Site
Higashiohmi-shi, 527-8505
Research Site
Iwakuni-shi, 740-8510
Research Site
Kanazawa, 920-8650
Research Site
Kasugai-shi, 487-0016
Research Site
Kishiwada-shi, 596-0042
Research Site
Kure-shi, 737-0023
Research Site
Kyoto, 612-8555
Research Site
Matsumoto-shi, 390-8621
Research Site
Minamiku, 861-4193
Research Site
Nagano, 399-8695
Research Site
Naha, 902-8511
Research Site
Ōita, 870-8511
Research Site
Ōmihachiman, 523-0082
Research Site
Otaru-shi, 047-8510
Research Site
Sagamihara-shi, 252-5188
Research Site
Toshima-ku, 171-0014
Research Site
Ueda-shi, 386-8610
Research Site
Uwajima-shi, 798-8510
Research Site
Yokohama, 245-8575

Other trials in Japan

France14 sites

Research Site
Bayonne, 64100
Research Site
Dijon, 21079
Research Site
La Tronche, 38043
Research Site
Le Coudray, 28630
Research Site
Montauban, 82017
Research Site
Montpellier, 34295
Research Site
Paris, 75010
Research Site
Paris, 75015
Research Site
Pierre-Bénite, 69495
Research Site
Rennes, 35033
Research Site
Saint-Brieuc, 22027
Research Site
Toulon, 83100
Research Site
Toulouse, 31059
Research Site
Tourcoing, 59208

Other trials in France

Taiwan12 sites

Research Site
Kaohsiung City, 807
Research Site
Kaohsiung City, 81362
Research Site
Kaohsiung City, 833
Research Site
Taichung, 40201
Research Site
Taichung, 40447
Research Site
Taichung, 40705
Research Site
Tainan, 70403
Research Site
Tainan, 710
Research Site
Taipei, 100
Research Site
Taipei, 110
Research Site
Taipei
Research Site
Taoyuan, 333

Other trials in Taiwan

Brazil11 sites

Research Site
Brasília, 72145-450
Research Site
Campina Grande do Sul, 83430000
Research Site
Campinas, 13060-080
Research Site
Campinas, 13092133
Research Site
Canoas, 92425-020
Research Site
Curitiba, 80730-150
Research Site
Porto Alegre, 90035-903
Research Site
Ribeirão Preto, 14026-020
Research Site
Ribeirão Preto, 14051-140
Research Site
Rio de Janeiro, 22061-080
Research Site
São Paulo, 01228-200

Other trials in Brazil

Bulgaria11 sites

Research Site
Blagoevgrad, 2700
Research Site
Pleven, 5804
Research Site
Plovdiv, 4003
Research Site
Sofia, 1202
Research Site
Sofia, 1309
Research Site
Sofia, 1407
Research Site
Sofia, 1431
Research Site
Sofia, 1527
Research Site
Sofia, 1606
Research Site
Sofia, 1784
Research Site
Varna, 9000

Other trials in Bulgaria

Poland11 sites

Research Site
Bydgoszcz, 85-079
Research Site
Lublin, 20-044
Research Site
Rzeszów, 35-055
Research Site
Skierniewice, 96-100
Research Site
Tarnów, 33-100
Research Site
Tczew, 83-110
Research Site
Tychy, 43-100
Research Site
Warsaw, 02-677
Research Site
Warsaw, 02-758
Research Site
Warsaw, 04-749
Research Site
Wołomin, 05-200

Other trials in Poland

Czechia10 sites

Research Site
Brno, 625 00
Research Site
Broumov, 55001
Research Site
Jaroměř, 551 01
Research Site
Kolín, 280 02
Research Site
Louny, 440 01
Research Site
Pilsen, 320 00
Research Site
Prague, 110 00
Research Site
Prague, 121 11
Research Site
Příbram, 261 01
Research Site
Zlín, 760 01

Other trials in Czechia

Russia9 sites

Research Site
Aramil, 624002
Research Site
Kemerovo, 650002
Research Site
Moscow, 119991
Research Site
Moscow, 121205
Research Site
Moscow, 121552
Research Site
Novosibirsk, 630055
Research Site
Perm, 614007
Research Site
Saint Petersburg, 195067
Research Site
Tver', 170036

Other trials in Russia

Canada8 sites

Research Site
Chicoutimi, Quebec, G7H 7K9
Research Site
Guelph, Ontario, N1H 1B1
Research Site
Newmarket, Ontario, L3Y 2P6
Research Site
North York, Ontario, M9N 1W4
Research Site
Ottawa, Ontario, K1Y 4W7
Research Site
Toronto, Ontario, M6G 1M2
Research Site
Trois-Rivières, Quebec, G9A 4P3
Research Site
Waterloo, Ontario, N2T 0C1

Other trials in Canada

Sweden8 sites

Research Site
Gothenburg, 413 45
Research Site
Jönköping, 551 85
Research Site
Lund, 222 21
Research Site
Norrköping, 603 79
Research Site
Örebro, 701 85
Research Site
Stockholm, 118 83
Research Site
Stockholm, 171 76
Research Site
Stockholm, 18288

Other trials in Sweden

Belgium7 sites

Research Site
Aalst, 9300
Research Site
Dendermonde, 9200
Research Site
Hasselt, 3500
Research Site
Huy, 4500
Research Site
Kortrijk, 8500
Research Site
Leuven, 3000
Research Site
Roeselare, 8800

Other trials in Belgium

Denmark7 sites

Research Site
Århus N, 8200
Research Site
Copenhagen, 2300
Research Site
Copenhagen O, 2100
Research Site
Hvidovre, 2650
Research Site
København NV, 2400
Research Site
Roskilde, 4000
Research Site
Viborg, 8800

Other trials in Denmark

Slovakia7 sites

Research Site
Banská Bystrica, 974 01
Research Site
Bratislava, 821 07
Research Site
Brezno, 977 01
Research Site
Košice, 04022
Research Site
Košice, 044 24
Research Site
Nitra, 949 01
Research Site
Prešov, 080 01

Other trials in Slovakia

Netherlands5 sites

Research Site
's-Hertogenbosch, 5223 GZ
Research Site
Amsterdam, 1081 HV
Research Site
Deventer, 7416 SE
Research Site
Heerlen, 6419 PC
Research Site
The Hague, 2545 AA

Other trials in Netherlands

Australia4 sites

Research Site
Bedford Park, 5042
Research Site
Chermside, 4032
Research Site
Concord, 2139
Research Site
Frankston, 3199

Other trials in Australia

Hungary4 sites

Research Site
Balatonfüred, 8230
Research Site
Budapest, 1096
Research Site
Budapest, 1122
Research Site
Nyíregyháza, 4400

Other trials in Hungary

Turkey (Türkiye)2 sites

Research Site
Eskişehir, 26480
Research Site
Izmir, 35340

Other trials in Turkey (Türkiye)

About this study

Official title: A Randomised, Double-blind, Placebo-controlled, Multi-center Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 Administered for Up to 48 Weeks in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%

Conditions: Heart Failure With Preserved Ejection Fraction
Being tested: AZD4831, Placebo
Keywords: Heart failure, Heart failure with preserved ejection fraction, HFpEF
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD4831Drug
AZD4831
PlaceboOther
Placebo

Study groups in NCT04986202
Study group	Role	What they receive
Part A 2.5 mg	Experimental	AZD4831 2.5 mg Receives: Drug: AZD4831
Part A 5 mg	Experimental	AZD4831 5 mg Receives: Drug: AZD4831
Part A Placebo	Placebo comparator	Placebo Receives: Other: Placebo
Part B Dose based on Part A	Experimental	AZD4831 Dose based on Part A Receives: Drug: AZD4831
Part B Placebo	Placebo comparator	Placebo Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Kansas City Cardiomyopathy Questionnaire -Total Symptom Score
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 16 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome
Measured: Baseline - 16 weeks
Six Minute Walk Distance
Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A
Measured: Baseline - 16 weeks

Secondary outcomes (9)

Kansas City Cardiomyopathy Questionnaire-Total Symptom Score
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 24 and 48 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome.
Measured: Baseline - 24 and 48 weeks
Six Minute Walk Distance
Six Minute Walk Distance change from baseline at 24 and 48 weeks compared with placebo Part A
Measured: Baseline - 24 and 48 weeks
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
NT-proBNP change from baseline at 16, 24, and 48 weeks compared with placebo Part A
Measured: Baseline - 16, 24 and 48 weeks
Left Ventricular Global Longitudinal Strain (LV-GLS)
LV-GLS change from baseline at 16 and 24 weeks compared with placebo Part A.
Left ventricular global longitudinal strain (LV-GLS) is an echocardiographic measure expressing longitudinal shortening as a percentage. A negative change from baseline indicates a better outcome.
Measured: Baseline - 16 and 24 weeks
Left Atrial Volume Index (LAVI)
LAVI change from baseline at 16 and 24 weeks compared with placebo Part A.
Left atrial volume index (LAVI) is an echocardiographic measure calculated by dividing LA volume by body surface area. A negative change from baseline indicates a better outcome.
Measured: Baseline - 16 and 24 weeks
Left Ventricular Mass Index (LVMI)
LVMI change from baseline at 16 and 24 weeks compared with placebo Part A.
Left ventricular mass index (LVMI) is an echocardiographic measure calculated by dividing LVM by body surface area. A negative change from baseline indicates a better outcome.
Measured: Baseline - 16 and 24 weeks
Pharmacokinetics (AZD4831 Plasma Exposure)
Plasma concentrations of AZD4831 summarised by timepoint and dose level Part A
Measured: Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks
High Sensitivity CRP (hsCRP)
hsCRP change from baseline at 16, 24, and 48 weeks compared with placebo Part A
Measured: Baseline - 16, 24 and 48 weeks
Interleukin 6 (IL-6)
IL-6 change from baseline at 16, 24, and 48 weeks compared with placebo Part A
Measured: Baseline - 16, 24 and 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jun 202127 Mar 2024

First posted2 Aug 2021
Study start30 Jun 2021
Primary completion27 Mar 2024
Study completion27 Mar 2024

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.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
More trials run by AstraZenecaThe 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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 711 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04986202
Sponsor's protocol ID: D6580C00010
Other IDs: 2020-005844-47
Acronym: ENDEAVOR
Status last verified: Jul 2025
First submitted: 18 Jun 2021
Last updated: 27 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Publications

Lund LH, Lam CSP, Pizzato PE, Michaelsson E, Mattsson A, Ericsson H, Aurell M, Collen A, Trebski M, Whatling C, Bergh N, Vavere AL, Hartman RJG, Cohen-Solal A, Chiang CE, Drelich G, Goudev A, Hudec M, Janssens S, Saraiva JFK, Kober L, Merkely B, Mielniczuk L, Toman O, Sanders-van Wijk S, Baldus S, Shah SJ. Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial. Nat Med. 2026 Sep 9. doi: 10.1038/s41591-026-04615-z. Online ahead of print.
PubMed 42717033
Lund LH, Lam CSP, Pizzato PE, Gabrielsen A, Michaelsson E, Nelander K, Ericsson H, Holden J, Folkvaljon F, Mattsson A, Collen A, Aurell M, Whatling C, Baldus S, Drelich G, Goudev A, Merkely B, Bergh N, Shah SJ. Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction. Eur J Heart Fail. 2023 Sep;25(9):1696-1707. doi: 10.1002/ejhf.2977. Epub 2023 Aug 22.
PubMed 37470101

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Placebo-controlled, Multi-center Sequential Phase 2b and Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 Administered for Up to 48 Weeks in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%
ClinicalTrials.gov ID: NCT04986202
Acronym / sponsor ID: ENDEAVOR / D6580C00010
Conditions: Heart Failure With Preserved Ejection Fraction
Keywords: Heart failure, Heart failure with preserved ejection fraction, HFpEF
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 711 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 30 Jun 2021 (actual)
Primary completion: 27 Mar 2024 (actual)
Study completion: 27 Mar 2024 (actual)
First posted: 2 Aug 2021 (actual)
Results: Posted 27 Aug 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 5

Arm	Type	Receives
Part A 2.5 mg	Experimental	Drug: AZD4831AZD4831 2.5 mg
Part A 5 mg	Experimental	Drug: AZD4831AZD4831 5 mg
Part A Placebo	Placebo comparator	Other: PlaceboPlacebo
Part B Dose based on Part A	Experimental	Drug: AZD4831AZD4831 Dose based on Part A
Part B Placebo	Placebo comparator	Other: PlaceboPlacebo

Who may qualify

Ages: 40 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (32 listed)

Part A
≥ 40 to ≤ 85 years of age, at the time of signing the informed consent.
Documented stable symptomatic HF (New York Heart Association Class II-IV) for at least 1 month at Screening (Visit 1) (transient HF in the setting of an MI does not qualify), with a medical history of typical symptoms of HF and receiving optimal therapy for HF as determined by the health-care physician.
LVEF > 40% at Screening (Visit 1). All participants will undergo a local echocardiogram at the Screening (Visit 1) with central reading to confirm the LVEF > 40% eligibility criteria before randomisation.
6MWD ≥ 30 meters and ≤ 400 meters at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.

Key exclusion criteria (26 listed)

Part A
1 eGFR < 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).
2. Systolic blood pressure < 90 mmHg or ≥ 160 mmHg if not on treatment with ≥ 3 blood pressure lowering medications or ≥ 180 mmHg irrespective of treatments at Randomisation
3. Heart rate > 110 bpm or < 50 bpm at Randomisation
4. Life expectancy < 3 years due to other reasons than cardiovascular disease.

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
AZD4831AZD4831	Drug	Part A 2.5 mg, Part A 5 mg, Part B Dose based on Part A
PlaceboPlacebo	Other	Part A Placebo, Part B Placebo

Primary outcome

Kansas City Cardiomyopathy Questionnaire -Total Symptom Score
Time frame: Baseline - 16 weeks
Kansas City Cardiomyopathy Questionnaire -Total Symptom Score change from baseline at 16 weeks compared with placebo Part A. The score ranges from 0 to 100, where a higher score represents a better patient outcome
Six Minute Walk Distance
Time frame: Baseline - 16 weeks
Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A

9 secondary outcomes

Kansas City Cardiomyopathy Questionnaire-Total Symptom Score
Time frame: Baseline - 24 and 48 weeks
Six Minute Walk Distance
Time frame: Baseline - 24 and 48 weeks
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Time frame: Baseline - 16, 24 and 48 weeks
Left Ventricular Global Longitudinal Strain (LV-GLS)
Time frame: Baseline - 16 and 24 weeks
Left Atrial Volume Index (LAVI)
Time frame: Baseline - 16 and 24 weeks
Left Ventricular Mass Index (LVMI)
Time frame: Baseline - 16 and 24 weeks
Pharmacokinetics (AZD4831 Plasma Exposure)
Time frame: Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks, 48 weeks, 52 weeks
High Sensitivity CRP (hsCRP)
Time frame: Baseline - 16, 24 and 48 weeks
Interleukin 6 (IL-6)
Time frame: Baseline - 16, 24 and 48 weeks

Results and safety

Results posted to the registry on 27 Aug 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD4831 2.5 mg	235	218
AZD4831 5 mg	240	234
Placebo	236	220

Primary outcome: Kansas City Cardiomyopathy Questionnaire -Total Symptom Score

Time frame: Baseline - 16 weeks. Least squares mean (95% Confidence Interval). Unit: Points

Measure	AZD4831 2.5 mg n = 211	AZD4831 5 mg n = 221	Placebo n = 220
Value	10.70 (8.58 to 12.82)	9.81 (7.73 to 11.90)	11.62 (9.54 to 13.71)

AZD4831 2.5 mg: Mean Difference (Final Values): -0.92 (95% CI -3.86 to 2.02), p = 0.537, ANCOVA
AZD4831 5 mg: Mean Difference (Final Values): -1.81 (95% CI -4.71 to 1.09), p = 0.221, ANCOVA

Population analysed: All participants who have been randomised to study treatment and who have received at least one dose of investigational product are included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

Primary outcome: Six Minute Walk Distance

Time frame: Baseline - 16 weeks. Least squares mean (95% Confidence Interval). Unit: Meters

Measure	AZD4831 2.5 mg n = 210	AZD4831 5 mg n = 223	Placebo n = 223
Value	15.3 (9.4 to 21.2)	18.2 (12.4 to 23.9)	12.9 (7.2 to 18.7)

AZD4831 2.5 mg vs Placebo: Mean Difference (Final Values): 2.4 (95% CI -5.7 to 10.5), p = 0.559, ANCOVA
AZD4831 5 mg vs Placebo: Mean Difference (Final Values): 5.3 (95% CI -2.7 to 13.3), p = 0.195, ANCOVA

Population analysed: All participants who have been randomised to study treatment and who have received at least one dose of investigational product were included irrespective of their protocol adherence and continued participation in the study and with non-missing data at baseline and the analysis timepoint. Participants were analysed according to their randomised study medication assignment, irrespective of the treatment actually received.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: The on-study period (Baseline - 52 weeks). The on-study period for is calculated from the date of the first dose of IP and to the earliest date of withdrawal of consent or date of death. If withdrawal of consent or death did not occur, it is calculated from the date of the first dose of IP and to the last study visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD4831 2.5 mg	60 of 234 (25.6%)	49 of 234 (20.9%)	10 of 234
AZD4831 5 mg	57 of 240 (23.8%)	44 of 240 (18.3%)	3 of 240
Placebo	56 of 235 (23.8%)	45 of 235 (19.1%)	10 of 235

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42717033Lund LH, Lam CSP, Pizzato PE, Michaelsson E, Mattsson A, Ericsson H, Aurell M, Collen A, Trebski M, Whatling C, Bergh N, Vavere AL, Hartman RJG, Cohen-Solal A, Chiang CE, Drelich G, Goudev A, Hudec M, Janssens S, Saraiva JFK, Kober L, Merkely B, Mielniczuk L, Toman O, Sanders-van Wijk S, Baldus S, Shah SJ. Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial. Nat Med. 2026 Sep 9. doi: 10.1038/s41591-026-04615-z. Online ahead of print.
Derived from this study: PubMed 37470101Lund LH, Lam CSP, Pizzato PE, Gabrielsen A, Michaelsson E, Nelander K, Ericsson H, Holden J, Folkvaljon F, Mattsson A, Collen A, Aurell M, Whatling C, Baldus S, Drelich G, Goudev A, Merkely B, Bergh N, Shah SJ. Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction. Eur J Heart Fail. 2023 Sep;25(9):1696-1707. doi: 10.1002/ejhf.2977. Epub 2023 Aug 22.
Redacted\_CSPLink provided by the sponsor.
Redacted CSR synopsisLink provided by the sponsor.
D6580C00010\_Redacted\_SAPLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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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.

The record lists no contact. Use the official record to reach the sponsor.

171 sites in 18 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing AZD4831 in people with Heart Failure With Preserved Ejection Fraction, run by AstraZeneca at 171 sites in 18 countries.

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 32 inclusion and 26 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 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 171 sites in United States, Japan, France, Taiwan, Brazil and 13 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 27 Aug 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?

Kansas City Cardiomyopathy Questionnaire -Total Symptom Score (time frame: Baseline - 16 weeks). 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?

On the ClinicalTrials.gov record for NCT04986202, which also lists 2 linked publications.

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 27 Aug 2025.