LCZ696 in Advanced LV Hypertrophy and HFpEF

Heart Failure Clinical Trial

Official title:

Sacubitril/Valsartan (LCZ696) in Patients With Advanced Hypertensive Left Ventricular Hypertrophy and Heart Failure With Preserved Ejection Fraction: Clinical, Haemodynamic and Neurohumoral Effects (a Phase 2, Randomized, Single-center, Parallel Group Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03928158
• Other study ID #: AAAA-A18-118022290061-2
• Status: Recruiting
• Phase: Phase 2
• Start date: May 31, 2019
• Est. completion date: November 30, 2022

Study information

• Verified date: January 2022
• Source: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
• Contact: Artem Ovchinnikov, MD, PhD
• Phone: +74954146612
• Email: artcardio[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with advanced LVH and HFpEF will be randomly assigned in open-label fashion to receive LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily, and will be treated for 24 weeks.

Description:

Heart failure with preserved ejection fraction (HFpEF) has a significant morbidity and mortality, and therapies that have proven effective in HF with reduced EF have not been shown to improve long-term prognosis in HFpEF. Inhibition of circulating neprilysin could augment deficient NP-receptor GC signaling and therefore be beneficial in HFpEF, as suggested by the decrease in NP following administration of valsartan/sacubitril in the phase 2 (PARAMOUNT study). Use of valsartan/sacubitril is currently being tested in the multicenter PARAGON-HF trial with HFpEF patients. The investigators suppose the best candidates for LCZ696 therapy will be patients with HFpEF and advanced concentric LV hypertrophy and obesity, i.e. having the lowest BNP bioavailability.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: November 30, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi =109 g/m² in women and =132 g/m² in men);

2. New York Heart Association (NYHA) class II-III heart failure;

3. Left ventricular ejection fraction > 50%;

4. Increased LV filling pressures assessed at rest or at peak exercise by echocardiography

5. Body mass index (BMI) > 30 kg/m²

6. Signed and data informed consent

Exclusion Criteria:

1. Age = 18 years;

2. Evidence of myocardial ischemia during stress echocardiography;

3. Chronic atrial flutter or atrial fibrillation;

4. Alternative cause of left ventricular hypertrophy and impaired diastolic function (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis and etc.);

5. NYHA classification I or decompensated heart failure at screening;

6. Systolic blood pressure < 110 mmHg or > 180 mmHg;

7. Diastolic blood pressure < 40 mmHg or > 100 mmHg;

8. Anemia (Hb < 100 g/l);

9. Significant left sided structural valve disease;

10. Secondary hypertension;

11. Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;

12. Myocardial infarction or myocardial revascularization within the last 3 months of screening;

13. Stroke or TIA within the last 3 months of screening;

14. Autoimmunic and oncological diseases;

15. Impaired renal function, defined as eGFR < 30 ml/min/1.73 m²;

16. Impaired liver function;

17. Potassium concentration >5.2 mmol/L.

Related Conditions & MeSH terms

• Essential Hypertension
• Heart Failure
• Hypertrophy

Intervention

Drug:
• LCZ 696
50-100-200 mg tablet
• Valsartan
40-80-160 mg tablet

Locations

Country	Name	City	State
Russian Federation	National Medical Research Center for Cardiology	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation	Ministry of Health of Russian Federation

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 6-minute walking distance (6MWD)	Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in exercise time during diastolic stress-test (DST)	Difference in exercise time during DST between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in left atrial volume index (LAVI)	Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in average E/e' ratio	Difference in E/e' ratio assessed by echocardiography both at rest and at peak exercise during diastolic stress test (DST) between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change estimated pulmonary artery systolic pressure (PASP)	Difference in PASP assessed by echocardiography at peak exercise both at rest and at peak exercise during diastolic stress test (DST) between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in left ventricular mass index (LVMI)	Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change of New York Heart Association (NYHA) functional classification	Difference in NYHA class between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score	Difference in MLHFQ score between 24 weeks after baseline and at baseline. The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses. Score ranges from 0 (best quality of life) to 105 (worst quality of life).	24 weeks
Secondary	Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)	Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in high-sensitivity C-reactive protein (hsCRP)	Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in carboxyterminal propeptide of type I collagen (PICP)	DIfference in PICP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in carboxyterminal telopeptide of type I collagen (CITP)	Difference in CITP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in N-Propeptide Of Type III Procollagen (PIIINP)	Difference in PIIINP plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Growth/differentiation factor 15 (GDF-15)	Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in sST2	Difference in sST2 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in Galectin-3	Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline	24 weeks
Secondary	Change in monocyte chemoattractant-1 (MCP-1)	DIfference in MCP-1 plasma levels between 24 weeks after baseline and at baseline	24 weeks