Clinical trial to compare the effectiveness of two medications in patients at risk of heart failure

Phase 1

• Conditions: 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.; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-002928-53-IE
• Lead Sponsor: The Heartbeat Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-10
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

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

1.A history of heart failure.
2.Asymptomatic left ventricular systolic dysfunction defined as LVEF <50% on most recent measurement.
3.Systolic blood pressure <100mmHg
4.Persistent atrial fibrillation.
5.History of hypersensitivity, allergy or intolerance to LCZ696, ARB or neprilysin therapy or to any of the excipients or other contraindication to their use.
6.Previous history of intolerance to recommended target doses for ARBs
7.Subjects who require treatment with both an ACE inhibitor and an ARB
8.Presence of haemodynamically significant mitral and /or aortic valve disease.
9.Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
10.Conditions that are expected to compromise survival over the study period.
11.Serum potassium level > 5.2 mmol/L at screening.
12.Severe renal insufficiency (eGFR <30 mL per minute per 1.73 m2).
13.Hepatic dysfunction (AST or ALT > 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the impact of LCZ696 (ARNI) versus angiotensin receptor blocker (ARB) (valsartan) on left ventricular diastolic function over 18 months.<br>;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<br>;Secondary Objective: 1.To assess the impact of LCZ696 versus valsartan therapy on atrial and ventricular structure and function over 9 and 18 months. <br>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.