Caution - Investigational Drug; Limited by United States Law to Investigational use only.
Caution - Investigational Drug; Limited by United States Law to Investigational use only.
TRUE- AHF Phase III clinical trial

TRUE- AHF Phase III clinical trial

TRUE-AHF (TRial of  Ularitide’s Efficacy and safety in patients with  Acute  Heart  Failure) is a Phase III, multicentre, randomised, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of ularitide as an IV infusion in addition to conventional therapy in patients suffering from acute heart failure (AHF). The study is currently in the process of recruiting participants from 190 centres in North America, Europe and Latin America and intends to recruit approximately 2,116 patients with AHF.

Study aim

  • The goal of TRUE-AHF will be to evaluate the efficacy and safety of ularitide on clinical status and mortality outcomes of patients with AHF.
  • TRUE-AHF aims to build on the growing body of evidence to treat patients suffering from AHF as early as possible, and will encourage heart failure experts, cardiologists and emergency physicians to work hand-in-hand to ensure an early enrolment of patients within the first hours after presentation to the hospital.

Study design

Study design

Patients will be randomised within 12 hours after clinical assessment at the emergency room. Following randomisation, patients will receive a 48 hour infusion of either ularitide 15 ng/kg/min or matching placebo (1:1 ratio) in a double-blind manner. In addition, patients will receive all appropriate therapy, that may include: vasoldilatory, intropic and diuretic support as clinically indicated. However, nesiritide, levosimendan, milrone, or any other phosphodiesterase will not be administered. Clinical data for the primary efficacy endpoints will be assessed at six, 24 and 48 hours from the start of the infusion. Safety parameters will be assessed during hospitalisation and adverse events (AEs) and serious adverse events (SAEs) will be evaluated until 30 days after the start of therapy.

Pathway TRUE-AHF

First co-primary efficacy endpoint

Assessment of the clinical composite will be performed at six, 24 and 48 hours after the start of ularitide IV infusion. Patients will be classified as ‘improved’ if the patients are:

  • Moderately or markedly improved at all three time points (at six, 24 and 48 hours) and do not fulfil criteria for ‘worse’ during the first 48 hours following the start of the study drug infusion Patients will be classified as ‘worse’ if (during the 48 hours) they: 
    • Die
    • Experience worsening heart failure requiring a pre-specified intervention at any time during the first 48 hours
    • Experience moderate or marked worsening of their global assessment at any of the three time points (at six, 24 or 48 hours)
Primary Efficacy Endpoint in TRUE-AHF

Second co-primary endpoint

  • Freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.

Secondary endpoints

  • Secondary Endpoint [ Time Frame: 48 hours post infusion start ] [ Designated as safety issue: No ] Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP) at 48 h of treatment compared to baseline.       
  • Secondary Endpoint [ Time Frame: 90 days after start of study drug infusion, including patients still hospitalized at Day 30 ] [ Designated as safety issue: No ] All-cause mortality and cardiovascular rehospitalization 
  • Secondary Endpoint [ Time Frame: 90 days after start of study drug infusion, including patients still hospitalized at Day 30 ] [ Designated as safety issue: No ] Cardiovascular rehospitalization
TRUE- AHF Phase III clinical trial