Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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30 June 2019 |
Main ID: |
EUCTR2016-003410-28-PT |
Date of registration:
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29/03/2017 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Study to evaluate the effect of LCZ696 compared to individualized medical therapy for comorbidities in Heart Failure with preserved Ejection Fraction (HFpEF) patients
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Scientific title:
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A 24-week, randomized, double-blind, multi-center, parallel group, active controlled study to evaluate the effect of LCZ696 on NT-proBNP, exercise capacity, symptoms and safety compared to individualized medical management of comorbidities in patients with heart failure and preserved ejection fraction |
Date of first enrolment:
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05/06/2017 |
Target sample size:
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2500 |
Recruitment status: |
Authorised-recruitment may be ongoing or finished |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003410-28 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Argentina
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Austria
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Belgium
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Brazil
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Bulgaria
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Canada
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Colombia
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Czech Republic
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Denmark
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Estonia
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France
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Germany
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Guatemala
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Hungary
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India
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Ireland
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Israel
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Italy
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Latvia
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Lithuania
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Mexico
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Netherlands
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Peru
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Portugal
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Romania
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Russian Federation
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Serbia
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Slovakia
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Spain
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Thailand
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Turkey
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United Kingdom
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United States
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Contacts
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Name:
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Clinical Trial Information Desk
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Address:
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Avenida Professor Doutor Cavaco Silva, nº10E
2740-255
Porto Salvo
Portugal |
Telephone:
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+351 21 000 86 00 |
Email:
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ensaios.clinicos@novartis.com |
Affiliation:
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Novartis Farma - Produtos Farmacêuticos, S.A. |
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Name:
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Clinical Trial Information Desk
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Address:
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Avenida Professor Doutor Cavaco Silva, nº10E
2740-255
Porto Salvo
Portugal |
Telephone:
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+351 21 000 86 00 |
Email:
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ensaios.clinicos@novartis.com |
Affiliation:
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Novartis Farma - Produtos Farmacêuticos, S.A. |
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Key inclusion & exclusion criteria
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Inclusion criteria: - Left ventricular ejection fraction (LVEF) >40% by echo within 6 months prior to study entry or during the screening epoch
- Symptom(s) of heart failure (HF) requiring treatment with diuretics (including loop, or thiazide diuretics, or mineralocorticoid antagonist [MRAs]) for at least 30 days prior to study entry
- NYHA class II-IV
- Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram.
- NT-proBNP > 220 pg/mL for patients with no atrial fibrillation/atrial flutter (AF) or >600 pg/mL for patients with AF
- KCCQ clinical summary score < 75
- Patients on ACEi or ARB therapy must have a history of HTN
Other protocol-defined inclusion criteria may apply. 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 403 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2097
Exclusion criteria: - Any prior measurement of LVEF = 40% under stable conditions
- Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention (PCI) within 3 months or an elective PCI within 30 days prior to study entry
- Any clinical event within the 6 months prior to Visit 1 that could have reduced the LVEF (e.g. MI, coronary artery bypass graft [CABG]), unless an echo measurement was performed after the event confirming the LVEF to be > 40%
- Current (within 30 days from visit 1) acute decompensated HF requiring therapy.
- Current (within 30 days from visit 1) use of renin inhibitor(s), dual RAS blockade or LCZ696
- History of hypersensitivity to LCZ696 or its components
- Patients with a known history of angioedema
- Walking distance primarily limited by non-cardiac comorbid conditions at visit 1
- Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dL males and < 9.5 g/dL
females, or body mass index (BMI) > 40 kg/m2.
- Systolic blood pressure (SBP) = 180 mmHg at study entry, or SBP >150 mmHg and <180 mmHg at study entry unless the patient is receiving 3 or more
antihypertensive drugs, or SBP < 110 mmHg at study entry.
- Patients with HbA1c > 7.5% not treated for diabetes
- Patients with prior major organ transplant or intent to transplant (ie on transplant list)
- eGFR < 30 ml/min/1.73 m2 as measured by MDRD at screening
- Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at study entry
- History or presence of any other disease with a life expectancy of < 3 years
- Pregnant or nursing women or women of childbearing potential unless they are using highly effective methods of contraception.
Other protocol-defined exclusion criteria may apply.
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Heart Failure with preserved Ejection Fraction (HFpEF) MedDRA version: 20.0
Level: LLT
Classification code 10019279
Term: Heart failure
System Organ Class: 100000004849
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Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
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Intervention(s)
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Trade Name: Entresto Product Name: LCZ696 50 mg Product Code: LCZ696 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: sacubitril/valsartan Other descriptive name: SACUBITRIL VALSARTAN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use
Trade Name: Entresto Product Name: LCZ696 100 mg Product Code: LCZ696 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: sacubitril/valsartan Other descriptive name: SACUBITRIL VALSARTAN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use
Trade Name: Entresto Product Name: LCZ696 200 mg Product Code: LCZ696 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: sacubitril/valsartan Other descriptive name: SACUBITRIL VALSARTAN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use
Trade Name: Diovan Product Name: Diovan 80 mg Pharmaceutical Form: Film-coated tablet INN or Proposed INN: VALSARTAN CAS Number: 137862-53-4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 80- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use
Trade Name: Diovan Product Name: Diovan 160 mg Pharmaceutical Form: Film-coated tablet INN or Proposed INN: VALSARTAN CAS Number: 137862-53-4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 160- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use
Trade Name: Diovan Product Name: Diovan 40 mg Pharmaceutical Form: Film-coated tablet INN or Proposed INN: VALSARTAN CAS Number: 137862-53-4 Concentration uni
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Primary Outcome(s)
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Secondary Objective: - To compare LCZ696 to individualized medical therapy for comorbidities on mean change from baseline of KCCQ clinical summary score (CSS) at Week 24 - To compare LCZ696 to individualized medical therapy for comorbidities on proportion of patients with = 5-points change in KCCQ CSS at Week 24 (= 5-points deterioration and separate analyses for = 5-points improvement) - To compare LCZ696 to individualized medical therapy for comorbidities in improving functional capacity as assessed by the 6-minute walk test (6 MWT) at Week 24 - To compare LCZ696 to individualized medical therapy for comorbidities in improving NYHA functional class at Week 24 - To compare LCZ696 to individualized medical therapy for comorbidities in improving symptoms as assessed by The Short Form (36) Health Survey (SF-36) physical component summary (PCS) score at Week 24
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Main Objective: To demonstrate that LCZ696 is superior to individualized medical therapy for comorbidities in reducing NTproBNP from baseline after 12 weeks of treatment in patients with HFpEF
To demonstrate that LCZ696 is superior to individualized medical therapy for comorbidities in improving exercise capacity as assessed by the six-minute walk test (6MWT) at Week 24 in a subset of patients
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Timepoint(s) of evaluation of this end point: baseline, week 12 baseline, week 24
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Primary end point(s): Change from baseline in N-terminal pro-brain natriuretic peptide (NTproBNP) after 12 weeks
Change from baseline in six-minute walk distance (6MWD) at Week 24.
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Secondary Outcome(s)
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Secondary end point(s): - Mean change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
- Percentage of patients with = 5-points deterioration in KCCQ CSS at Week 24
- Percentage of patients with = 5-points improvement in KCCQ CSS at Week 24
- Change from baseline in the 6-minute walk test (6MWT) to week 24
- Change in NYHA functional class from baseline to week 24
- Change from baseline in SF- 36 physical component summary (PCS) score score to week 24
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Timepoint(s) of evaluation of this end point: baseline, week 24
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Secondary ID(s)
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CLCZ696D2302
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Source(s) of Monetary Support
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Novartis Pharma AG
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Ethics review
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Status: Approved
Approval date:
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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