Study to Evaluate the Efficacy and Safety of AZD4831 in Participants with Heart Failure With Left Ventricular Ejection Fraction > 40%
- Conditions
- Heart Failure
- Registration Number
- JPRN-jRCT2031210194
- Lead Sponsor
- Ageishi Yuji
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
1. 40 to 85 years of age, at the time of signing the informed consent.
2. 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 signs and symptoms of HF and receiving optimal therapy for HF as determined by the health-care physician
3. 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.
4. 6MWD 30 meters or more and 400 meters or less at Screening (Visit 1) and Randomisation (Visit 3). Difference in 6MWD between Screening and Randomisation must be < 50 meters.
5. KCCQ-TSS 90 points or more at Screening (Visit 1) and Randomisation (Visit 3).
6. NT-proBNP 250 pg/mL (sinus rhythm) or more, or 500 pg/mL (atrial fibrillation/flutter) or less at Screening (Visit 1) for patients with BMI 30 kg/m2 or less.
NT-proBNP 200 pg/mL (sinus rhythm) or more or 400 pg/mL (atrial fibrillation/flutter) or less 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:
(a). 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 more or LA length 5.0 cm or more, or LA area 20 cm2 or more, or LA volume 55 mL or more, or LAVI > 34 mL/m2. Left ventricular hypertrophy is defined by septal thickness or posterior wall thickness 1.1 cm or more, or LVMI > 95 g/m2 in women and > 115 g/m2 in men.
(b). Spectral tissue Doppler echocardiography - E/e' ratio (average of septal and lateral) 13 or more at rest at the echocardiogram performed at Screening (Visit 1).
(c). 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).
(d). 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.
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 or more if not on treatment with 3 blood pressure lowering or more medications or 180 mmHg irrespective of treatments at Randomisation or more
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).
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% or less.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 more), or any clinically significant thyroid disease as judged by the investigator.
18. ALT or AST 2 or more x 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part A are change from baseline in KCCQ-TSS and 6MWD at 16 weeks compared with placebo. <br>Part B are change from baseline in KCCQ-TSS and 6MWD at 24 weeks compared with placebo.
- Secondary Outcome Measures
Name Time Method