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

Domingo Pascual-Figal, Rolf Wachter, Michele Senni, Jan Belohlavek, Adele Noè, David Carr, Dmytro Butylin, Domingo Pascual-Figal, Rolf Wachter, Michele Senni, Jan Belohlavek, Adele Noè, David Carr, Dmytro Butylin

Abstract

Aims: The 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.

Trial registration: ClinicalTrials.gov NCT02661217.

Keywords: Acute decompensated heart failure; Acute heart failure; Discharge; Hospitalization; LCZ696; Sacubitril/valsartan.

© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
TRANSITION study design. Study visits take place at 2, 4, 6, 8, and 10 weeks and 14, 18, 22, and 26 weeks after randomization (or at the point of premature treatment or study discontinuation). ACEI, angiotensin‐converting enzyme inhibitor; ADHF, acute decompensated heart failure; ARB, angiotensin receptor blocker; HFrEF, heart failure with reduced rejection fraction; OMT, optimized medical treatment as per treating physician; Sac/Val, sacubitril/valsartan.
Figure 2
Figure 2
Dosing schedule for sacubitril/valsartan (Sac/Val) in the TRANSITION study. ACEI, angiotensin‐converting enzyme inhibitor; ALT, alanine transaminase; ARB, angiotensin receptor blocker; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; HF, heart failure.

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