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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/16/2021.

LCZ696 in Advanced LV Hypertrophy and HFpEF

Clinicaltrials.gov identifier NCT03928158

Recruitment Status Recruiting

First Posted April 26, 2019

Last update posted December 23, 2019

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.

  • Condition or Disease:Heart Failure
    Essential Hypertension
  • Intervention/Treatment: Drug: LCZ 696
    Drug: Valsartan
  • Phase: Phase 2
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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 60 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • 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)
  • Actual Study Start Date: May 2019
  • Estimated Primary Completion Date: November 2020
  • Estimated Study Completion Date: November 2020
Arms and interventions
Arm Intervention/treatment
Experimental: LCZ 696
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)
Drug: LCZ 696
50-100-200 mg tablet
Active Comparator: Valsatran
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)
Drug: Valsartan
40-80-160 mg tablet
Outcome Measures
  • Primary Outcome Measures: 1. Change in 6-minute walking distance (6MWD) [ Time Frame: 24 weeks ]
    Difference in distance walked during 6-minute walking test (6MWT) between 24 weeks after baseline and at baseline
  • Secondary Outcome Measures: 1. Change in high-sensitivity C-reactive protein (hsCRP) [ Time Frame: 24 weeks ]
    Difference in hsCRP plasma levels between 24 weeks after baseline and at baseline
  • 2. Change in carboxyterminal propeptide of type I collagen (PICP) [ Time Frame: 24 weeks ]
    DIfference in PICP plasma levels between 24 weeks after baseline and at baseline
  • 3. Change in carboxyterminal telopeptide of type I collagen (CITP) [ Time Frame: 24 weeks ]
    Difference in CITP plasma levels between 24 weeks after baseline and at baseline
  • 4. Change in exercise time during diastolic stress-test (DST) [ Time Frame: 24 weeks ]
    Difference in exercise time during DST between 24 weeks after baseline and at baseline
  • 5. Change in left atrial volume index (LAVI) [ Time Frame: 24 weeks ]
    Difference in LAVI assessed by echocardiography between 24 weeks after baseline and at baseline
  • 6. Change in average E/e' ratio [ Time Frame: 24 weeks ]
    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
  • 7. Change estimated pulmonary artery systolic pressure (PASP) [ Time Frame: 24 weeks ]
    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
  • 8. Change in left ventricular mass index (LVMI) [ Time Frame: 24 weeks ]
    Difference in LVMI assessed by echocardiography between 24 weeks after baseline and at baseline
  • 9. Change of New York Heart Association (NYHA) functional classification [ Time Frame: 24 weeks ]
    Difference in NYHA class between 24 weeks after baseline and at baseline
  • 10. Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) score [ Time Frame: 24 weeks ]
    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).
  • 11. Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) [ Time Frame: 24 weeks ]
    Difference in NT-proBNP plasma levels between 24 weeks after baseline and at baseline
  • 12. Change in N-Propeptide Of Type III Procollagen (PIIINP) [ Time Frame: 24 weeks ]
    Difference in PIIINP plasma levels between 24 weeks after baseline and at baseline
  • 13. Change in Growth/differentiation factor 15 (GDF-15) [ Time Frame: 24 weeks ]
    Difference in GDF-15 plasma levels between 24 weeks after baseline and at baseline
  • 14. Change in sST2 [ Time Frame: 24 weeks ]
    Difference in sST2 plasma levels between 24 weeks after baseline and at baseline
  • 15. Change in Galectin-3 [ Time Frame: 24 weeks ]
    Difference in Galectin-3 plasma levels between 24 weeks after baseline and at baseline
  • 16. Change in monocyte chemoattractant-1 (MCP-1) [ Time Frame: 24 weeks ]
    DIfference in MCP-1 plasma levels between 24 weeks after baseline and at baseline
Eligibility Criteria
  • Ages Eligible for Study: 40 to 80 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

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 180 mmHg;

7. Diastolic blood pressure 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 5.2 mmol/L.

Contacts and Locations
Contacts

Contact: Artem Ovchinnikov, MD, PhD +74954146612 artcardio@mail.ru

Locations

Russian Federation
National Medical Research Center for Cardiology
Moscow

Sponsors and Collaborators

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

Ministry of Health of Russian Federation

More Information
  • Responsible Party: National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
  • ClinicalTrials.gov Identifier: NCT03928158 History of Changes
  • Other Study ID Numbers: AAAA-A18-118022290061-2
  • First Posted: April 26, 2019 Key Record Dates
  • Last Update Posted: December 23, 2019
  • Last Verified: December 2019
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by National Medical Research Center for Cardiology, Ministry of Health of Russian Federation: left ventricular hypertrophy
    diastolic dysfunction
    LCZ696
    HFpEF
    LV filling pressures
    HF
  • Additional relevant MeSH terms: Heart Failure
    Essential Hypertension
    Hypertrophy