Back to resultsLCZ696 in Advanced LV Hypertrophy and HFpEF
Primary Purpose
Heart Failure, Essential Hypertension
Status
Recruiting
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
LCZ 696
Valsartan
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring left ventricular hypertrophy, diastolic dysfunction, LCZ696, HFpEF, HF, LV filling pressures
Eligibility Criteria
Inclusion Criteria:
- Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi ≥109 g/m² in women and ≥132 g/m² in men);
- New York Heart Association (NYHA) class II-III heart failure;
- Left ventricular ejection fraction > 50%;
- Increased LV filling pressures assessed at rest or at peak exercise by echocardiography
- Body mass index (BMI) > 30 kg/m²
- Signed and data informed consent
Exclusion Criteria:
- Age ≤ 18 years;
- Evidence of myocardial ischemia during stress echocardiography;
- Chronic atrial flutter or atrial fibrillation;
- Alternative cause of left ventricular hypertrophy and impaired diastolic function (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis and etc.);
- NYHA classification I or decompensated heart failure at screening;
- Systolic blood pressure < 110 mmHg or > 180 mmHg;
- Diastolic blood pressure < 40 mmHg or > 100 mmHg;
- Anemia (Hb < 100 g/l);
- Significant left sided structural valve disease;
- Secondary hypertension;
- Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;
- Myocardial infarction or myocardial revascularization within the last 3 months of screening;
- Stroke or TIA within the last 3 months of screening;
- Autoimmunic and oncological diseases;
- Impaired renal function, defined as eGFR < 30 ml/min/1.73 m²;
- Impaired liver function;
- Potassium concentration >5.2 mmol/L.
Sites / Locations
- National Medical Research Center for CardiologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
LCZ 696
Valsatran
Arm Description
Initial dose - 50 mg twice daily, up-titration to 200 mg twice daily. Patients will also receive standard therapy for heart failure (β-blockers, diuretics, MRAs)
Initial dose - 40 mg twice daily, up-titration to 160 mg twice daily. Patients also will receive standard therapy for heart failure (β-blockers, diuretics, MRAs)
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Change in exercise time during diastolic stress-test (DST)
Difference in exercise time during DST between 24 weeks after baseline and at baseline
Change in left atrial volume index (LAVI)
Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline
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
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
Change in left ventricular mass index (LVMI)
Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
Change of New York Heart Association (NYHA) functional classification
Difference in NYHA class between 24 weeks after baseline and at baseline
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).
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
Change in high-sensitivity C-reactive protein (hsCRP)
Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline
Change in carboxyterminal propeptide of type I collagen (PICP)
DIfference in PICP plasma levels between 24 weeks after baseline and at baseline
Change in carboxyterminal telopeptide of type I collagen (CITP)
Difference in CITP plasma levels between 24 weeks after baseline and at baseline
Change in N-Propeptide Of Type III Procollagen (PIIINP)
Difference in PIIINP plasma levels between 24 weeks after baseline and at baseline
Change in Growth/differentiation factor 15 (GDF-15)
Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline
Change in sST2
Difference in sST2 plasma levels between 24 weeks after baseline and at baseline
Change in Galectin-3
Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline
Change in monocyte chemoattractant-1 (MCP-1)
DIfference in MCP-1 plasma levels between 24 weeks after baseline and at baseline
Full Information
NCT ID
NCT03928158
First Posted
April 23, 2019
Last Updated
January 10, 2022
Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Collaborators
Ministry of Health of Russian Federation
1. Study Identification
Unique Protocol Identification Number
NCT03928158
Brief Title
LCZ696 in Advanced LV Hypertrophy and HFpEF
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2019 (Actual)
Primary Completion Date
May 31, 2022 (Anticipated)
Study Completion Date
November 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Collaborators
Ministry of Health of Russian Federation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Essential Hypertension
Keywords
left ventricular hypertrophy, diastolic dysfunction, LCZ696, HFpEF, HF, LV filling pressures
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LCZ 696
Arm Type
Experimental
Arm Description
Initial dose - 50 mg twice daily, up-titration to 200 mg twice daily. Patients will also receive standard therapy for heart failure (β-blockers, diuretics, MRAs)
Arm Title
Valsatran
Arm Type
Active Comparator
Arm Description
Initial dose - 40 mg twice daily, up-titration to 160 mg twice daily. Patients also will receive standard therapy for heart failure (β-blockers, diuretics, MRAs)
Intervention Type
Drug
Intervention Name(s)
LCZ 696
Intervention Description
50-100-200 mg tablet
Intervention Type
Drug
Intervention Name(s)
Valsartan
Intervention Description
40-80-160 mg tablet
Primary Outcome Measure Information:
Title
Change in 6-minute walking distance (6MWD)
Description
Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in exercise time during diastolic stress-test (DST)
Description
Difference in exercise time during DST between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in left atrial volume index (LAVI)
Description
Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in average E/e' ratio
Description
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
Time Frame
24 weeks
Title
Change estimated pulmonary artery systolic pressure (PASP)
Description
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
Time Frame
24 weeks
Title
Change in left ventricular mass index (LVMI)
Description
Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change of New York Heart Association (NYHA) functional classification
Description
Difference in NYHA class between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score
Description
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).
Time Frame
24 weeks
Title
Change in N-terminal pro b-type natriuretic peptide (NT-proBNP)
Description
Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in high-sensitivity C-reactive protein (hsCRP)
Description
Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in carboxyterminal propeptide of type I collagen (PICP)
Description
DIfference in PICP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in carboxyterminal telopeptide of type I collagen (CITP)
Description
Difference in CITP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in N-Propeptide Of Type III Procollagen (PIIINP)
Description
Difference in PIIINP plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Growth/differentiation factor 15 (GDF-15)
Description
Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in sST2
Description
Difference in sST2 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in Galectin-3
Description
Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
Title
Change in monocyte chemoattractant-1 (MCP-1)
Description
DIfference in MCP-1 plasma levels between 24 weeks after baseline and at baseline
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Moderate/severe hypertensive left ventricular (LV) hypertrophy (LVMi ≥109 g/m² in women and ≥132 g/m² in men);
New York Heart Association (NYHA) class II-III heart failure;
Left ventricular ejection fraction > 50%;
Increased LV filling pressures assessed at rest or at peak exercise by echocardiography
Body mass index (BMI) > 30 kg/m²
Signed and data informed consent
Exclusion Criteria:
Age ≤ 18 years;
Evidence of myocardial ischemia during stress echocardiography;
Chronic atrial flutter or atrial fibrillation;
Alternative cause of left ventricular hypertrophy and impaired diastolic function (hypertrophic/restictive cardiomyopathy, aortic stenosis, constrictive pericarditis and etc.);
NYHA classification I or decompensated heart failure at screening;
Systolic blood pressure < 110 mmHg or > 180 mmHg;
Diastolic blood pressure < 40 mmHg or > 100 mmHg;
Anemia (Hb < 100 g/l);
Significant left sided structural valve disease;
Secondary hypertension;
Dyspnea due to non-cardiac causes such as pulmonary disease, anemia, severe obesity, primary valvular, or myocardial diseases;
Myocardial infarction or myocardial revascularization within the last 3 months of screening;
Stroke or TIA within the last 3 months of screening;
Autoimmunic and oncological diseases;
Impaired renal function, defined as eGFR < 30 ml/min/1.73 m²;
Impaired liver function;
Potassium concentration >5.2 mmol/L.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Artem Ovchinnikov, MD, PhD
Phone
+74954146612
Email
artcardio@mail.ru
Facility Information:
Facility Name
National Medical Research Center for Cardiology
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nursiyat Ibragimova, MD
Email
nursik0205@gmail.com
First Name & Middle Initial & Last Name & Degree
Nursiyat Ibragimova, MD
12. IPD Sharing Statement
Learn more about this trial
LCZ696 in Advanced LV Hypertrophy and HFpEF
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