Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF)
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|ClinicalTrials.gov Identifier: NCT01920711|
Recruitment Status : Completed
First Posted : August 12, 2013
Results First Posted : September 29, 2020
Last Update Posted : September 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure With Preserved Ejection Fraction||Drug: LCZ696 Drug: Valsartan||Phase 3|
This was a multicenter, randomized, double-blind, parallel group, active-controlled, study to evaluate the efficacy and safety of sacubitril/valsartan compared to valsartan, on morbidity and mortality in heart failure patients (NYHA Class II-IV) with preserved ejection fraction. Specifically, the study evaluated the effect of sacubitril/valsartan compared to the active comparator valsartan in the reduction of the rate of CV death and total HF hospitalizations in patients with HFpEF. The trial consisted of two periods: (1) a single-blind treatment run-in epoch that lasted from 3 to 8 weeks, in which patients received valsartan 80 mg bid, followed by sacubitril/valsartan 100 mg bid and (2) a double-blind randomized treatment epoch (sacubitril/valsartan 200 mg bid or valsartan 160 mg bid). In this study, investigators were responsible for assessing and submitting all events which could potentially fulfill the criteria for the primary, secondary, or other clinical endpoints to a Clinical Endpoint Committee (CEC). Investigator reported events were assessed by the CEC for adjudication.
For angioedema or angioedema-like events, investigators completed an Adjudication Questionnaire for an Angioedema-like Event form. All angioedema reports were forwarded to an Angioedema Adjudication Committee (AAC) by Novartis for assessment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4822 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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 (PARAGON-HF)|
|Actual Study Start Date :||July 18, 2014|
|Actual Primary Completion Date :||June 7, 2019|
|Actual Study Completion Date :||June 7, 2019|
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. Target dose of LCZ696 during the double blind period is 200 mg b.i.d.
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. Target dose of Valsartan during the double blind period is 160 mg b.i.d.
Valsartan 40mg, 80mg and 160mg dosage strengths will be available for dose adjustments.
- 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) ]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.
- Change in the Clinical Summary Score From Baseline to Month 8 by Kansas City Cardiomyopathy Questionnaire (KCCQ) [ Time Frame: Baseline, 8 months ]The KCCQ is a validated instrument for self-assessment of quality of life and health status in heart failure (HF) patients. The clinical summary score, which is derived from the physical limitations and heart failure (HF) symptoms domains of the KCCQ is a valid measure for assessing the patient's health aspects that may be influenced by CV medications. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. Evaluation of change from baseline to month 8 in KCCQ a most sensitive, specific, and responsive health-related quality of life measure for heart failure symptoms and physical limitations.
- Change From Baseline to Month 8 in New York Heart Association (NYHA) Functional Class [ Time Frame: Baseline, 8 months ]Evaluation of change from baseline to Month 8 in NYHA functional class, a well established grading scale used to classify a heart failure's (HF) patients' level of functionality based on the signs and symptoms of HF exhibited by the patient.
- Participants With First Occurrence of a Composite Renal Endpoint [ Time Frame: Randomization to total follow-up time (up to 57 months) ]Analyis of composite renal endpoint defined as renal death, or reaching ESRD, or ≥50% decline in eGFR relative to baseline, using Cox's proportional hazards model.
- All-cause Mortality [ Time Frame: Randomization to total follow up time (up to 57 months) ]Analysis for all-cause mortality using Cox's proportional hazards model.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01920711
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|