NCT03066804.

Trial name or title	A Randomized, Double‐blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients (PARALLAX)
Methods	Study design: parallel RCT, blinding: participant, care provider, investigator, outcomes assessor Anticipated start date: 29 September 2017 Anticipated completion date: 4 December 2019
Participants	Estimated enrolment: 2200 Inclusion criteria: Left ventricular ejection fraction (LVEF) ≥45% 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 or > 600 pg/mL for patients with atrial fibrillation KCCQ clinical summary score < 75 Patients on ACEi or ARB therapy must have a history of HTN Exclusion criteria: Any prior measurement of LVEF < 40% Acute coronary syndrome (including myocardial infarction), 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 (eg myocardial infarction, coronary artery bypass graft [CABG]), unless an echo measurement was performed after the event confirming the LVEF to be ≥ 40% and EF ≥ 45% by the time of screening Current acute decompensated HF requiring therapy. Current use of renin inhibitor(s) History of hypersensitivity to LCZ696 or its components Patients with a known history of angioedema Walking distance primarily limited by non‐cardiac comorbid conditions Alternative reason for shortness of breath such as: significant pulmonary disease or severe COPD, haemoglobin (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 (i.e. on transplant list) eGFR < 30 mL/min/1.73 m² as measured by MDRD at screening Serum potassium > 5.2 mmol/L at study entry History or presence of any other disease with a life expectancy of < 3 years Pregnant or nursing women or women of child‐bearing potential unless they are using highly effective methods of contraception Other protocol‐defined inclusion/exclusion criteria may apply.
Interventions	All patients who fulfill the inclusion/exclusion criteria will be stratified before randomization based upon prior therapy for comorbidities to one of 3 strata: ACEi, ARB or no RASi. Patients in the ACEi strata will receive LCZ696 or enalapril. Patients in the ARB strata will receive LCZ696 or valsartan. Patients in the no RASi strata will receive LCZ696 or matching placebo.
Outcomes	Primary: Change from baseline in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) after 12 weeks Secondary: Mean change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) [ Time Frame: baseline, week 24 ] Percentage of patients with ≥ 5‐points deterioration in KCCQ CSS at Week 24 [ Time Frame: baseline, week 24 ] Percentage of patients with ≥ 5‐points improvement in KCCQ CSS at Week 24 [ Time Frame: baseline, week 24 ] Change from baseline in the 6‐minute walk test (6MWT) to week 24 [ Time Frame: baseline, week 24 ] Change in NYHA functional class from baseline to week 24 [ Time Frame: baseline, week 24 ] Change from baseline in SF‐36 physical component summary (PCS) score to week 24 [ Time Frame: baseline, week 24 ]
Starting date	29 September 29 2017
Contact information	Novartis Pharmaceuticals (novartis.email@novartis.com)
Notes	Comparison of interest: LCZ696 or matching placebo Sponsor: Novartis Pharmaceuticals Other identifiers: CLCZ696D2302, 2016‐003410‐28 ( EudraCT Number)