Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

Abstract

AimsThe prognosis after hospitalization for acute decompensated heart failure (ADHF) remains poor, especially <30 days post‐discharge. Evidence‐based medications with prognostic impact administered at discharge improve survival and hospital readmission, but robust studies comparing pre‐discharge with post‐discharge initiation are rare. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with heart failure (HF) and reduced left ventricular ejection fraction (<40%) (rEF). In common with other landmark studies, it enrolled patients who were ambulatory at the time of inclusion. In addition, there is also still limited knowledge of initiation and up‐titration of sacubitril/valsartan in ACEi/ARB‐ naïve patients and in de novo HF with rEF patients.Methods and results TRANSITION is a multicentre, open‐label study in which ~1000 adults hospitalized for ADHF with rEF are randomized to start sacubitril/valsartan in a pre‐discharge arm (initiated ≥24 h after haemodynamic stabilization) or a post‐discharge arm (initiated within Days 1–14 after discharge). The protocol allows investigators to select the appropriate starting dose and dose adjustments according to clinical circumstances. Over a 10 week treatment period, the primary and secondary objectives assess the feasibility and safety of starting sacubitril/valsartan in‐hospital, early after haemodynamic stabilization. Exploratory objectives also include assessment of HF signs and symptoms, readmissions, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity troponin T levels, and health resource utilization parameters.Conclusions TRANSITION will provide new evidence about initiating sacubitril/valsartan following hospitalization for ADHF, occurring either as de novo ADHF or as deterioration of chronic HF, and in patients with or without prior ACEI/ARB therapy. The results of TRANSITION will thus be highly relevant to the management of patients hospitalized for ADHF with rEF.

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

“…Compared to PIONEER‐HF, patients enrolled in TRANSITION were, on average, 6 years older and suffered more from diabetes, coronary artery disease, previous myocardial infarction and atrial fibrillation, but less from hypertension (online supplementary Tables S3 and S4). Median NT‐proBNP at randomisation was lower in TRANSITION compared to PIONEER‐HF, owing to differences in the respective trial protocols . The differences in prior HF treatments received by patients in PIONEER‐HF and TRANSITION are explained by higher proportion of ACEI/ARB‐naïve patients recruited in PIONEER‐HF and the general lower use of mineralocorticoid receptor antagonists in the US …”

“…TRANSITION (NCT02661217) was a randomised, multicentre, open‐label study performed in 19 countries and 156 hospitals worldwide. The study design and rationale have been previously published . The study included male or female patients aged ≥ 18 years who were hospitalised for an episode of ADHF ( de novo HF or due to exacerbation of chronic HF), with New York Heart Association (NYHA) class II–IV, blood pressure ≥ 100 mmHg and left‐ventricular ejection fraction (LVEF) ≤ 40%.…”

“…The study design has two parts: starting with 10‐week treatment, and continuing with 16‐week follow‐up treatment, counting from randomisation. In this paper, the focus is on the initial 10‐week treatment …”

Characteristics and Treatments of Patients Enrolled in the CHAMP‐HF Registry Compared With Patients Enrolled in the PARADIGM‐HF Trial

“…Ongoing clinical trials, including the PIONEER‐HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT‐Pro‐BNP in Patients Stabilized From an Acute Heart Failure Episode) study9 and the TRANSITION (Comparison of Pre‐ and Post‐Discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event) study,10 will provide valuable information about the efficacy and safety of sacubitril/valsartan in patients with a recent episode of acute HF.…”

In‐hospital initiation of sacubitril/valsartan in acute decompensated heart failure: being in the right place at the right time

“…The TRANSITION study was an international, prospective, multicentre, randomized, open‐label clinical trial performed at 156 sites in 19 countries. The study enrolled patients ≥ 18 years of age hospitalized for a primary diagnosis of ADHF with an ejection fraction ≤ 40%, New York Heart Association functional class II–IV symptoms, and a systolic blood pressure (SBP) ≥ 100 mmHg.…”