Patients (asymptomatic) with cardiovascular risk factors for heart failure including either hypertension and/or type II diabetes, with elevated levels of natriuretic peptide (brain natriuretic peptide (BNP) between 20 and 280pg/ml or NT-proBNP values between 100 pg/ml and 1,000 pg/ml) and left atrial volume index (LAVI) > 28 mL/m2.
Conditions
Interventions
Product Name: LCZ696 (50mg)
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Trade Name: Diovan (40mg)
Pharmaceutica
Sponsors
The Heartbeat Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age > 40yrs with cardiovascular risk factor(s) including at least one of: a. History of hypertension (medicated for greater than one month); b. History of diabetes; BNP between 20 and 280pg/ml or NT-proBNP values between 100 pg/ml and 1,000 pg/ml within 6 months prior to screening LAVI > 28 mL/m2 obtained during Doppler Echocardiography within 6 months prior to screening Subjects must give written informed consent to participate in the study and before any study related assessments are performed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 125 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 125
Exclusion criteria
Exclusion criteria: 1. A history of heart failure. 2. Asymptomatic left ventricular systolic dysfunction defined as LVEF 5.2 mmol/L at screening. 12. Severe renal insufficiency (eGFR 3 times the upper limit of normal (ULN)) 14. Concomitant use of aliskiren 15. History of angioedema. 16. History or evidence of drug or alcohol abuse within the last 12 months 17. Malignancy or presence of any other disease with a life expectancy of < 2 years 18. Women who are pregnant, breast-feeding, or women of child bearing potential not using estro-progestative oral or intra-uterine contraception or implants, or women using estro-progestative oral or intra-uterine contraception or implants but who consider stopping it during the planned duration of the study. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. (Contraception must be continued for one week following discontinuation of study drug). 19. Concomitant participation in other intervention trials 20. Participation in any investigational drug trial within one month of visit 1. 21. Refusal to provide informed consent 22. Subjects with contraindications to MRI a) Brain aneurysm clip b) Implanted neural stimulator c) Implanted cardiac pacemaker or defibrillator d) Cochlear implant e) Ocular foreign body (e.g. metal shavings) f) Other implanted medical devices: (e.g. Swan-Ganz catheter) g) Insulin pump h) Metal shrapnel or bullet. 23. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs, including but not limited to any of the following: a) History of major gastrointestinal tract surgery including gastrectomy, gastroenterostomy, or bowel resection. b) Inflammatory bowel disease during the 12 months prior to Visit 1. c) Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase. d) Evidence of hepatic disease as determined by any one of the following: SGOT or SGPT values exceeding 3 x ULN at Visit 1, a history of hepatic encephalopathy, a history of oesophageal varices, or a history of portocaval shunt.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the impact of LCZ696 (ARNI) versus angiotensin receptor blocker (ARB) (valsartan) on left ventricular diastolic function over 18 months. ;Primary end point(s): Change in left atrial volume index (LAVI) measured by Cardiac Magnetic Resonance Imaging (cMRI) over 18 months;Timepoint(s) of evaluation of this end point: 18 months ;Secondary Objective: 1. To assess the impact of LCZ696 versus valsartan therapy on atrial and ventricular structure and function over 9 and 18 months. 2. To assess the impact of LCZ696 versus valsartan therapy on cardiovascular and non-cardiovascular adverse events, including prior to and post onset of Covid19 pandemic. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Left ventricular function using Doppler Echocardiography (average E/e’) between baseline and 18 months 2. Left atrial volume index (Doppler Echocardiography LAV)/BSA* between baseline and 9 months 3. Left atrial function measured as total cMRI LAEF ((LAVimax-LAVimin)/LAVimax) over 18 months 4. Left atrial function measured as cMRI left atrial stroke volume index (LAVmax-LAVmin)/BSA*, or LAVimax-LAVimin over 18 months 5. Left ventricular structure (cMRI LVMi indexed to BSA*) over 18 months 6. Left ventricular function (cMRI LVEF) over 18 months 7. Measures of vascular compliance (ABPM pulse pressure) between baseline and 18 months 8. Change in log transformed NT-proBNP between baseline and 18 months 9. Time to first all cardiovascular death and major adverse cardiac events (MACE) requiring hospitalisation over 18 months. MACE includes arrthymia (including atrial fibrillation/flutter), transient ischaemic attack, stroke, valvular heart disease, myocardial infarction, peripheral or pulmonary thrombosis/embolus or heart failure *BSA calculated using the DuBois formula ;Timepoint(s) of evaluation of this end point: 9 and 18 months | — |
Countries
Ireland
Contacts
Public ContactDirector of Clinical Trials
The Heartbeat Trust
Outcome results
None listed