Table 2.

Currently undergoing clinical trials of sacubitril-valsartan.

Trial name (identifier)	Type, phase	Study start–end	n	Study population	Intervention	Control arm	Primary endpoint	Secondary endpoint	Duration of study
PARAGON-HF (NCT01920711)31	RCT, phase III	July 2014–March 2019	4829	HFpEF, elevated NT-proBNP, structural heart disease	sacubitril-valsartan	valsartan	Composite of CV death and total (first and recurrent) HF hospitalizations	Change in KCCQ score, change in NYHA functional class, time to first composite renal endpoint (renal death, ESRD, or ⩾50% decline in eGFR), time to all-cause mortality	57 months
PARALLEL-HF (NCT02468232)33	RCT, phase III	June 2015–November 2018	225	Same as PARADIGM-HF trial, Japanese population	sacubitril-valsartan	enalapril	Composite of CV death or HF hospitalization	Change in NT-proBNP; time to the first occurrence of CV death, HF hospitalization or intensification of treatments due to documented episode(s) of worsening HF; change in NYHA functional class; number patients with reported total adverse events, serious adverse events and death; composited of CV death and total of HF hospitalization; clinical composite score; time to all-cause mortality; number of hospitalized patient; number of hospital admission; number of days in ICU; number of re-hospitalization; number of emergency visits for HF; changes in NT-proBNP; changes in blood amino-terminal propeptide of procollagen type III; changes in urine cGMP	40 months
PARABLE (NCT02682719)34	RCT, phase II	December 2015–December 2018	250	Elevated NT-proBNP or NP:BNP ratio, LAVI > 28 ml/m2, CV risk factors	sacubitril-valsartan	valsartan	Change in LAVI at 18 months	Change in LAVI (by cardiac MRI and echocardiography) at 9 months; change in cardiac MRI and echocardiographic parameters of LV structure and function; change in NT-proBNP, urinary cGMP, markers of collagen turnover, marker of extracellular matrix turnover, myocardial damage (hs-Troponin T), fibrosis (soluble ST-2), inflammatory markers, and renal function (creatinine clearance)	18 months
TRANSITION (NCT02661217)35	RCT, phase IV	February 2016–March 2018	1000	HFrEF patients hospitalized for ADHF	Initiation of sacubitril-valsartan pre-discharge	Initiation of sacubitril-valsartan post-discharge (up to 14 days)	Percentage of patients taking target dose of sacubitril-valsartan 200 mg BID at 10 weeks post randomization	Number of patients who achieved and maintained either the dose of sacubitril-valsartan 100 mg or 200 mg BID for at least 2 weeks; number of patients who, regardless of previous dose changes, achieved any dose of sacubitril-valsartan BID for at least 2 weeks; percentage of patients permanently discontinued from treatment due to adverse events	26 weeks
PIONEER-HF (NCT02554890)36	RCT, phase IV	April 2016– April 2018	736	HFrEF patients hospitalized for ADHF	sacubitril-valsartan	enalapril	Percentage change from baseline in NT-proBNP	Incidence of symptomatic hypotension, hyperkalemia, angioedema; change in high sensitivity-troponin, urinary cGMP, BNP to NT-proBNP ratio	8 weeks
PARADISE-AMI (NCT02924727)37	RCT, phase III	April 2016–July 2019	4650	Post-MI with LVEF ⩽ 40%	sacubitril-valsartan	ramipril	Composite endpoint of CV death, HF hospitalization, or outpatient HF	Time to first occurrence of composite of CV death or HF hospitalization, composite of HF hospitalization or outpatient HF, composite of CV death, nonfatal spontaneous myocardial infarction or nonfatal stroke, total number of recurrent confirmed composite endpoints, time to all-cause mortality	32 months
PARTHENON (NCT02957409)38	Observational cohort	May 2016 –May 2021	1000	Canadian population taking sacubitril /valsartan	sacubitril-valsartan	None	All-cause hospitalization or all- cause mortality in relation to NT-proBNP or BNP levels	Rates of clinically relevant symptomatic hypotension, serum potassium >5.5 mmol/l, decrease in eGFR of ⩾40%, relationship between changes in NT-proBNP and all-cause mortality, all-cause hospitalization, and renal impairment	36 months
PARALLAX (NCT03066804)32	RCT, phase III	June 2017–December 2019	2200	HFpEF, NYHA class II–IV, KCCQ < 75, structural heart disease	sacubitril-valsartan	enalapril, valsartan, or placebo	Change in NT-proBNP	Change in KCCQ clinical summary score; percentage of patients with ⩾ 5-points deterioration or improvement in KCCQ CSS, change in the 6-minute walk test; change in NYHA functional class; change in SF-36 physical component summary score	24 weeks
PROVE-HF (NCT02887183)39	Open label single group	October 2016– October 2019	830	HFrEF, NYHA class II–IV, eligible for sacubitril/valsartan	sacubitril/valsartan	None	Correlation between changes in NT-proBNP and left ventricular end systolic and diastolic volume index, LVEF, and LAVI at 1 year	Primary outcome at 6 months, mean change in the KCCQ-23 clinical summary score from baseline to month 12	12 months
PERSPECTIVE (NCT02884206)40	RCT, phase III	November 2016–July 2021	520	HFpEF, NYHA class II–IV	sacubitril-valsartan	valsartan	Change in the CogState Global Cognitive Composite Score	Change in a cortical composite SUVr, individual cognitive domains, summary score of the IADL	156 weeks

ADHF, acute decompensated heart failure; BID, twice daily; BNP, B-type NP; c-GMP, cyclic-guanosine monophosphate; CKD, chronic kidney disease; CSS, symptoms and physical limitations; CV, cardiovascular; eGFR, estimated glomerular filtration rate; ESRD, end stage renal disease; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IADL, instrumental activities of daily living; ICU, intensive care unit; KCCQ, Kansas City Cardiomyopathy Questionnaire; LAVI, left atrial volume index; LV, left ventricle; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MRI, magnetic resonance imaging; N, number of patients in the trial; NP, natriuretic peptide; NT-pro BNP, N-terminal pro-brain natriuretic peptide; NYHA, New York Heart Association; RCT, randomized controlled trial; SUVr, standardized uptake value ratio.