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.
- 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.
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.
Primary efficacy endpoints
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:
- 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 safety endpoint
The primary safety endpoint for the TRUE-AHF trial is:
- All-cause mortality and cardiovascular re-hospitalisation at Day 30 after start of study drug infusion
The secondary endpoints are:
- Changes of levels of NT-pro BNP in the blood at 48 hours of treatment from baseline
- All-cause mortality and cardiovascular rehospitalisation at Day 90 after start of study drug infusion
- Cardiovascular mortality rate at Day 90
The exploratory endpoints are:
- Components of primary efficacy endpoint:
- Proportions improved/not improved and worse/not worse
- Proportions of patients alive
- Proportions of patients requiring an intervention for persistent or worsening heart failure
- Proportions of patients who are 'moderately or markedly improved'
- Combined risk of all-cause mortality or cardiovascular rehospitalisation at Day 60 and Day 180 after start of study drug infusion
- Changes in BP and heart rate during the first 72 hours from the start of the study drug infusion or hospital discharge, whatever comes first
- Length of stay of index hospitalisation in hours after start of study drug infusion
- Change in glomerular filtration rate (GFR) from baseline, as assessed by change in Modification of Diet in Renal Disease (MDRD) at 48 hours after start of the study infusion as compared to baseline
Further information on the TRUE-AHF study can be found in the study factsheet