Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF)
This study is currently recruiting participants.
(see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01920711
First received: August 8, 2013
Last updated: July 22, 2014
Last verified: July 2014
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Purpose
The purpose of this study is to evaluate the effect of LCZ696 compared to valsartan in the reduction of cardiovascular death and heart failure(HF) hospitalizations in patients with HF with preserved ejection fraction.
| Condition | Intervention | Phase |
|---|---|---|
|
Heart Failure With Preserved Ejection Fraction |
Drug: LCZ696 Drug: Valsartan |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients (NYHA Class II-IV) With Preserved Ejection Fraction |
Resource links provided by NLM:
MedlinePlus related topics:
Heart Failure
Drug Information available for:
Valsartan
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- Cumulative number of primary composite events of cardiovascular (CV) death and total (first and recurrent) HF hospitalizations. [ Time Frame: Total follow up time (up to 57 months) ] [ Designated as safety issue: No ]The primary objective of this study is to compare LCZ696 to valsartan in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF hospitalizations, in HF patients (New York Heart Association [NYHA] Class II-IV) with preserved ejection fraction (left ventricular ejection fraction [LVEF] ≥45%). The treatment arm with the lower rate of events will be deemed as having a successful response.
Secondary Outcome Measures:
- Cumulative number of events of the extended composite endpoint of CV death, total HF hospitalizations, total non-fatal strokes, and total non-fatal myocardial infarctions (MIs). [ Time Frame: Total follow up time (up to 57 months) ] [ Designated as safety issue: No ]Evaluation of the composite endpoint of CV death, total HF hospitalizations, total strokes, and total MIs. The treatment arm with the lower rate of events will be deemed a successful response.
- Change from baseline to Month 8 in New York Heart Association (NYHA) functional class [ Time Frame: Baseline, 8 months ] [ Designated as safety issue: No ]Evaluation of change from baseline to Month 8 in NYHA functional class, a well established grading scale used to classify a HF patients' level of functionality based on the signs and symptoms of HF exhibited by the patient
- Time to new onset of atrial fibrillation (AF) [ Time Frame: Total follow up time (up to 57 months) ] [ Designated as safety issue: No ]Evaluation of the time to onset of atrial fibrillation (AF) in patients wtihout prior AF (no prior history of AF and no AF at baseline).
- Time to all-cause mortality [ Time Frame: Total follow up time (up to 57 months) ] [ Designated as safety issue: No ]Evaluation of the time to all cause death.
| Estimated Enrollment: | 4300 |
| Study Start Date: | July 2014 |
| Estimated Study Completion Date: | May 2019 |
| Estimated Primary Completion Date: | May 2019 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: LCZ696
Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria.
|
Drug: LCZ696
LCZ696 50mg, 100mg and 200 mg dosage strengths will be available for dose adjustments.
|
|
Active Comparator: Valsartan
Single Blind Run-in Period (3-8 weeks): Patients will start on Valsartan 80 mg b.i.d. for 1-2 weeks followed by LCZ696 100 mg b.i.d. for 2-4 weeks prior to randomization into the Double Blind period (up to 57 months). Patients can only be randomized from the run-in period if they meet all of the run-in safety criteria.
|
Drug: Valsartan
Valsartan 40mg, 80mg and 160mg dosage strengths will be available for dose adjustments.
Other Name: Diovan
|
Eligibility| Ages Eligible for Study: | 55 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Left ventricular ejection fraction (LVEF) ≥45% prior to study entry.
- Symptom(s) of heart failure (HF) and requiring treatment with diuretic(s) for HF ≥30 days prior to study entry
- Current symptom(s) of HF
- Structural heart disease (left atrial enlargement or left ventricular hypertrophy) documented by echocardiogram
- At least one of the following: a HF hospitalization within 9 months prior to study entry and/or an elevated NT-proBNP.
Exclusion Criteria:
- Any prior measurement of LVEF < 45%.
- Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery within 3 months , or urgent percutaneous coronary intervention (PCI) within 30 days of entry.
- Patients who have had an MI, coronary artery bypass graft (CABG) or other event within the 6 months prior to entry unless an echo measurement performed after the event confirms a LVEF ≥45%.
- Current acute decompensated HF requiring therapy.
- Patients who require treatment with 2 or more of the following: an angiotensin converting enzyme inhibitor (ACEI), an angiotensin receptor blocker (ARB) or a renin inhibitor
- Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, hemoglobin (Hgb) <10 g/dl, or body mass index (BMI) > 40 kg/m2.
- Systolic blood pressure (SBP) ≥ 180 mmHg at entry, or SBP >150 mmHg and <180 mmHg at entry unless the patient is receiving 3 or more antihypertensive drugs.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01920711
Show 347 Study Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01920711
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | ||
| Contact: Novartis Pharmaceuticals |
Show 347 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01920711 History of Changes |
| Other Study ID Numbers: | CLCZ696D2301, 2013-001747-31 |
| Study First Received: | August 8, 2013 |
| Last Updated: | July 22, 2014 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Novartis:
|
Heart failure, preserved ejection fraction, diastolic heart failure |
Additional relevant MeSH terms:
|
Heart Failure Cardiovascular Diseases Heart Diseases Valsartan Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists |
Antihypertensive Agents Cardiovascular Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on February 27, 2015