Heart Failure
Conditions
Keywords
Acute Heart Failure, Inotropes, Lusitropic agents, Istaroxime, Debio 0614
Brief summary
The purpose of this study is to assess the safety and efficacy of istaroxime in patients hospitalized for Acute Decompensated Heart Failure (ADHF) not requiring inotropic therapy.This will be done by comparing the hemodynamic effect of a 24-hour infusion of three different doses of the drug versus placebo. Efficacy will be measured as a change in Pulmonary Capillary Wedge Pressure from pre-infusion to 6 hours after infusion start. Secondary objectives will include the evaluation of clinical efficacy and safety through assessment of cardiovascular and renal tolerability as well as changes in biological markers such as brain natriuretic peptide (BNP) and troponin I (TNI), and the neurohormones renin and aldosterone and also to assess the pharmacokinetics of istaroxime and its metabolites.
Detailed description
The 32-day study includes a 48-hour screening period, a 30-minute to 2-hour pre treatment period, a maximum 2-hour period for randomization and measurement of baseline values, a 24-hour treatment period, and a 96-hour post-treatment period. A 25-day follow-up period including a visit on Day 30 will take place after the active phase of the study When considered to be eligible, a first cohort of 88 patients will be randomized in a 3:1 ratio to receive 24-hrs treatment with istaroxime 0.5 μg/kg/min or placebo. If after the continuous safety monitoring and interim analyses the DMC determines that there are no safety issues with this dose, a second cohort of 88 patients will be randomized in a 3:1 ratio to receive 24-hrs treatment with istaroxime 1.0 μg/kg/min or placebo. If after the continuous safety monitoring and interim analyses of the second cohort the DMC determines that there are no safety issues with this dose, a third cohort of 88 patients will be randomized in a 3:1 ratio to receive 24-hrs treatment with istaroxime 1.5 μg/kg/min or placebo. In all cohorts, patients will receive standard of care therapy.
Interventions
DRUGIstaroxime
Istaroxime 0.5 μg/kg/min (30 μg/kg/h) continuous i.v. infusion for 24 hours
DRUGPlacebo
Placebo continuous i.v. infusion for 24 hours
Sponsors
Debiopharm International SA
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥18 years; * Admission for ADHF * Systolic blood pressure ≤ 120 mmHg; * Ejection fraction (EF) ≤ 35 % * Signed informed consent. Randomization inclusion criteria: * Persistence of ADHF signs despite initial treatment with i.v. diuretics and/or vasodilators; * Cardiac index ≤ 2.5 L/min/m²; * Pulmonary capillary wedge pressure ≥ 20 mmHg * Systolic BP between 85 and 120 mmHg (limits included) without signs or symptoms of hypoperfusion
Exclusion criteria
* Main screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PCWP change from baseline | 6 hours after infusion start |
Secondary
| Measure | Time frame |
|---|---|
| PCWP, MRAP, SVR, PVR, Cardiac Index and SBP | 1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end. |
| Safety parameters and drug pharmacokinetics | 1, 3, 6, 12 and 24 hours after infusion start and 1 and 3 hours after infusion end |
Outcome results
None listed