Study to Evaluate the Efficacy and Safety of AZD4831 in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40%
ENDEAVOR
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%
2 other identifiers
interventional
711
18 countries
171
Brief 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%. The study will consist of 2 separate parts, Part A and Part B, approximately 660 participants will be randomised in Part A, 820 in Part B.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2021
171 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2021
CompletedStudy Start
First participant enrolled
June 30, 2021
CompletedFirst Posted
Study publicly available on registry
August 2, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 27, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
March 27, 2024
CompletedResults Posted
Study results publicly available
August 27, 2025
CompletedAugust 27, 2025
July 1, 2025
2.7 years
June 18, 2021
March 26, 2025
August 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
Baseline - 16 weeks
Six Minute Walk Distance
Six Minute Walk Distance change from baseline at 16 weeks compared with placebo Part A
Baseline - 16 weeks
Secondary Outcomes (9)
Kansas City Cardiomyopathy Questionnaire-Total Symptom Score
Baseline - 24 and 48 weeks
Six Minute Walk Distance
Baseline - 24 and 48 weeks
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Baseline - 16, 24 and 48 weeks
Left Ventricular Global Longitudinal Strain (LV-GLS)
Baseline - 16 and 24 weeks
Left Atrial Volume Index (LAVI)
Baseline - 16 and 24 weeks
- +4 more secondary outcomes
Other Outcomes (5)
Adverse Events
Baseline - 52 weeks
Vital Signs
Baseline - 52 weeks
Clinical Laboratory (Haematology)
Baseline - 52 weeks
- +2 more other outcomes
Study Arms (5)
Part A 2.5 mg
EXPERIMENTALAZD4831 2.5 mg
Part A 5 mg
EXPERIMENTALAZD4831 5 mg
Part A Placebo
PLACEBO COMPARATORPlacebo
Part B Dose based on Part A
EXPERIMENTALAZD4831 Dose based on Part A
Part B Placebo
PLACEBO COMPARATORPlacebo
Interventions
Eligibility Criteria
You may qualify if:
- 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.
- MWD ≥ 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)
- 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.
- 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.
- Body mass index ≥ 18.0 kg/m2 and ≤ 45.0 kg/m2
- +17 more criteria
You may not qualify if:
- Part A
- eGFR \< 30 mL/min/1.73m2 (Chronic Kidney Disease-Epidemiology Collaboration formula) at Screening (Visit 1).
- \. 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
- \. Heart rate \> 110 bpm or \< 50 bpm at Randomisation
- \. Life expectancy \< 3 years due to other reasons than cardiovascular disease.
- \. History or ongoing allergy/hypersensitivity reactions to drugs (including but not limited to rash, angioedema, acute urticaria).
- \. Presence of any disease or condition rather than HF constituting the main reason for limiting the ability to exercise/reduced exercise capacity.
- \. Current decompensated HF and/or NT-proBNP \> 5000 pg/mL at Screening (Visit 1)
- \. 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
- \. Any planned cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter, valve repair/replacement, aortic aneurysm surgery, etc).
- \. 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.
- \. Hb \< 110 g/L (male) and \< 100 g/L (female) or iron-deficiency with/without anaemia requiring ongoing or planned IV iron treatment.
- \. 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.
- \. ALT or AST ≥ 2 × ULN at Screening (Visit 1).
- \. 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).
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (171)
Research Site
Alexander City, Alabama, 35010, United States
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Little Rock, Arkansas, 72205, United States
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Sacramento, California, 95821, United States
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Miami, Florida, 33144, United States
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Miami Beach, Florida, 33140, United States
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Ocala, Florida, 34471, United States
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Evanston, Illinois, 60208, United States
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Hazel Crest, Illinois, 60429, United States
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Shreveport, Louisiana, 71105, United States
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Baltimore, Maryland, 21229, United States
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St Louis, Missouri, 63136, United States
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Buffalo, New York, 14215, United States
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New York, New York, 10019, United States
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Rosedale, New York, 11422, United States
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Chapel Hill, North Carolina, 27599, United States
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Pinehurst, North Carolina, 28374, United States
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Cleveland, Ohio, 44195, United States
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Philadelphia, Pennsylvania, 19107, United States
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Knoxville, Tennessee, 37916, United States
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Tullahoma, Tennessee, 37388, United States
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Norfolk, Virginia, 23510, United States
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Bedford Park, 5042, Australia
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Chermside, 4032, Australia
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Concord, 2139, Australia
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Frankston, 3199, Australia
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Aalst, 9300, Belgium
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Dendermonde, 9200, Belgium
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Hasselt, 3500, Belgium
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Huy, 4500, Belgium
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Kortrijk, 8500, Belgium
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Leuven, 3000, Belgium
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Roeselare, 8800, Belgium
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Brasília, 72145-450, Brazil
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Campina Grande do Sul, 83430000, Brazil
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Campinas, 13060-080, Brazil
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Campinas, 13092133, Brazil
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Canoas, 92425-020, Brazil
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Curitiba, 80730-150, Brazil
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Porto Alegre, 90035-903, Brazil
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Ribeirão Preto, 14026-020, Brazil
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Ribeirão Preto, 14051-140, Brazil
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Rio de Janeiro, 22061-080, Brazil
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São Paulo, 01228-200, Brazil
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Blagoevgrad, 2700, Bulgaria
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Pleven, 5804, Bulgaria
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Plovdiv, 4003, Bulgaria
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Sofia, 1202, Bulgaria
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Sofia, 1309, Bulgaria
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Sofia, 1407, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1527, Bulgaria
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Sofia, 1606, Bulgaria
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Sofia, 1784, Bulgaria
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Varna, 9000, Bulgaria
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Guelph, Ontario, N1H 1B1, Canada
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Newmarket, Ontario, L3Y 2P6, Canada
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North York, Ontario, M9N 1W4, Canada
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Ottawa, Ontario, K1Y 4W7, Canada
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Toronto, Ontario, M6G 1M2, Canada
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Waterloo, Ontario, N2T 0C1, Canada
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Chicoutimi, Quebec, G7H 7K9, Canada
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Trois-Rivières, Quebec, G9A 4P3, Canada
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Brno, 625 00, Czechia
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Broumov, 55001, Czechia
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Jaroměř, 551 01, Czechia
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Kolín, 280 02, Czechia
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Louny, 440 01, Czechia
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Pilsen, 320 00, Czechia
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Prague, 110 00, Czechia
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Prague, 121 11, Czechia
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Příbram, 261 01, Czechia
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Zlín, 760 01, Czechia
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Århus N, 8200, Denmark
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Copenhagen, 2300, Denmark
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Copenhagen O, 2100, Denmark
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Hvidovre, 2650, Denmark
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København NV, 2400, Denmark
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Roskilde, 4000, Denmark
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Viborg, 8800, Denmark
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Bayonne, 64100, France
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Dijon, 21079, France
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La Tronche, 38043, France
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Le Coudray, 28630, France
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Montauban, 82017, France
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Montpellier, 34295, France
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Paris, 75010, France
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Paris, 75015, France
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Pierre-Bénite, 69495, France
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Rennes, 35033, France
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Saint-Brieuc, 22027, France
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Toulon, 83100, France
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Toulouse, 31059, France
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Tourcoing, 59208, France
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Balatonfüred, 8230, Hungary
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Budapest, 1096, Hungary
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Budapest, 1122, Hungary
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Nyíregyháza, 4400, Hungary
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Fukui-shi, 910-8526, Japan
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Higashiohmi-shi, 527-8505, Japan
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Iwakuni-shi, 740-8510, Japan
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Kanazawa, 920-8650, Japan
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Kasugai-shi, 487-0016, Japan
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Kishiwada-shi, 596-0042, Japan
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Kure-shi, 737-0023, Japan
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Kyoto, 612-8555, Japan
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Matsumoto-shi, 390-8621, Japan
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Minamiku, 861-4193, Japan
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Nagano, 399-8695, Japan
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Naha, 902-8511, Japan
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Otaru-shi, 047-8510, Japan
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Ōita, 870-8511, Japan
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Ōmihachiman, 523-0082, Japan
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Sagamihara-shi, 252-5188, Japan
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Toshima-ku, 171-0014, Japan
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Ueda-shi, 386-8610, Japan
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Uwajima-shi, 798-8510, Japan
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Yokohama, 245-8575, Japan
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's-Hertogenbosch, 5223 GZ, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Deventer, 7416 SE, Netherlands
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Heerlen, 6419 PC, Netherlands
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The Hague, 2545 AA, Netherlands
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Bydgoszcz, 85-079, Poland
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Lublin, 20-044, Poland
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Rzeszów, 35-055, Poland
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Skierniewice, 96-100, Poland
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Tarnów, 33-100, Poland
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Tczew, 83-110, Poland
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Tychy, 43-100, Poland
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Warsaw, 02-677, Poland
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Warsaw, 02-758, Poland
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Warsaw, 04-749, Poland
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Wołomin, 05-200, Poland
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Aramil, 624002, Russia
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Kemerovo, 650002, Russia
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Moscow, 119991, Russia
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Moscow, 121205, Russia
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Moscow, 121552, Russia
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Novosibirsk, 630055, Russia
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Perm, 614007, Russia
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Saint Petersburg, 195067, Russia
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Tver', 170036, Russia
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Banská Bystrica, 974 01, Slovakia
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Bratislava, 821 07, Slovakia
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Brezno, 977 01, Slovakia
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Košice, 04022, Slovakia
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Košice, 044 24, Slovakia
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Nitra, 949 01, Slovakia
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Prešov, 080 01, Slovakia
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Gothenburg, 413 45, Sweden
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Jönköping, 551 85, Sweden
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Lund, 222 21, Sweden
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Norrköping, 603 79, Sweden
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Örebro, 701 85, Sweden
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Stockholm, 118 83, Sweden
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Stockholm, 171 76, Sweden
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Stockholm, 18288, Sweden
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Kaohsiung City, 807, Taiwan
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Kaohsiung City, 81362, Taiwan
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Kaohsiung City, 833, Taiwan
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Taichung, 40201, Taiwan
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Taichung, 40447, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Tainan, 710, Taiwan
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Taipei, 100, Taiwan
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Taipei, 110, Taiwan
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Taipei, Taiwan
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Taoyuan District, 333, Taiwan
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Eskişehir, 26480, Turkey (Türkiye)
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Izmir, 35340, Turkey (Türkiye)
Related Publications (1)
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.
PMID: 37470101DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 18, 2021
First Posted
August 2, 2021
Study Start
June 30, 2021
Primary Completion
March 27, 2024
Study Completion
March 27, 2024
Last Updated
August 27, 2025
Results First Posted
August 27, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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.