Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure (TRUE-AHF)
Acute Decompensated Heart Failure
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Ularitide (Urodilatin) Intravenous Infusion in Patients Suffering From Acute Decompensated Heart Failure [TRUE-AHF]|
- Two Co-primary Efficacy Endpoints [ Time Frame: 6, 24, 48 hours post infusion through the entire duration of the trial ] [ Designated as safety issue: No ]
Improvement in a hierarchical clinical composite comprised of elements associated with: patient global assessment using a 7-point scale of symptomatic improvement, lack of improvement, or worsening; persistent or worsening heart failure (HF) requiring an intervention (initiation or intensification of IV therapy, circulatory or ventilatory mechanical support, surgical intervention, ultrafiltration, hemofiltration or dialysis); and all-cause mortality. Assessment of the clinical composite will be performed at 6 hour (h), 24 h and 48 h after start of IV ularitide infusion
Freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.
- Length of stay of index hospitalization in hours after start of study drug infusion [ Time Frame: up to 30 days ] [ Designated as safety issue: No ]
- Length of stay in intensive care (intensive care unit [ICU] or critical care unit [CCU]) [ Time Frame: during the first 120 h following the start of the study drug infusion. ] [ Designated as safety issue: No ]
- Number of events of persistent or worsening HF requiring an intervention [ Time Frame: from the start of the study drug infusion to 120 h. ] [ Designated as safety issue: No ]
- Proportion of patients with persistent or worsening HF and requiring an intervention [ Time Frame: from the start of study drug infusion to 120 h. ] [ Designated as safety issue: No ]
- Reduction in rehospitalization for heart failure [ Time Frame: within 30 days after initial hospital ] [ Designated as safety issue: No ]
- Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP) [ Time Frame: 48 h of treatment compared to baseline. ] [ Designated as safety issue: No ]
- Time to completion of last dose of any IV drugs that can be used for the treatment of HF (e.g., diuretics, vasodilators, or positive inotropic agents) [ Time Frame: for the first 120 h following the start of the drug infusion. ] [ Designated as safety issue: No ]
- Change in serum creatinine [ Time Frame: from baseline through 72 h. ] [ Designated as safety issue: No ]
- 180 days after start of study drug infusion, including patients still hospitalized at Day 30. [ Time Frame: All-cause mortality and cardiovascular rehospitalization ] [ Designated as safety issue: No ]
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||February 2016|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Ularitide, lyophilizate for i.v. infusion, 15 ng/kg BW/min, for 48 hours
Placebo Comparator: Placebo
Placebo lyophilizate for i.v. infusion
The objective of the TRUE-AHF study is to evaluate the effect of a 48-h continuous IV infusion of ularitide (15 ng/kg/min) versus placebo on the clinical status of patients with acute decompensated heart failure (ADHF).
The study drug will be administered in addition to the standard treatment. The nature of standard therapy will be carried out according to the clinical judgment of the Investigator and may include vasodilator, inotropic, and diuretic drugs, as clinically indicated.
There are two co-primary endpoints for this study. Co-primary endpoint 1 will be a hierarchical clinical composite variable that includes a patient-centered assessment of clinical progress, an assessment of lack of improvement or worsening of HF requiring a pre-specified intervention, and death.
The endpoint is intended to mimic the assessment that would be carried out by a physician caring for the patient. If, during the 48 h infusion, a patient's clinical course deteriorates because he/she dies, fails to improve or develops worsening HF requiring a pre-specified intervention or if the patient considers his/her general clinical status as moderately or markedly worse, the patient will be considered to be "worse". If the patient considers his/her general clinical status as moderately or markedly improved and if such improvement is sustained without fulfilling the criteria for "worse" throughout the 48-h infusion (from 0 h to 48 h), the patient will be considered to be "improved". If the patient is neither improved nor worse, the patient's clinical status will be considered to be "unchanged".
Co-primary efficacy endpoint 2 evaluates freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01661634
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|Study Chair:||Milton Packer, MD|
|Principal Investigator:||Christopher O'Connor, MD|
|Principal Investigator:||William F. Peacock, MD|