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A randomized, double-blind, Multicenter, parallel, placebo-controlled study
The purpose of the study is to evaluate the efficacy, safety and tolerability of intravenous infusion of Levosimendan for 24hrs in patients with ADHF who will be hospitalized with ADHF and continue to have symptom of dyspnea at rest(NYHA Class III or IV) despite with treatment of SOCs(include intravenous diuretics, vasodilators and/or positive inotropic drugs but except amrinone and milrinone) within 48hrs
Efficacy is measured by Clinical composite classification(Improved, No change, Worse), bio-marker(change of BNP and ST-2), Patient's Global Assessment, NYHA functional Classification, hospitalization period and renal function tests(change of creatinine, BUN and NGAL) Safety is measured by recording the incidence of adverse events(AEs), vital signs, clinical blood safety tests(biochemistry, hematology) and concomitant medications
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SIMDAX | Experimental | Levosimendan2.5mg/mL |
|
| SIMDAX Placebo | Placebo Comparator | Water for injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simdax | Drug | Levosimendan2.5mg/ml |
|
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of the Clinical Composite Classification(CCC) | Assessment of the Clinical Composite Classification(CCC) using the Patients Global Assessment(PGA) at 5day after start of IV levosiemendan or Placebo infusion with WHF through 5dyas: Improved, Unchanged, Worse | 5day |
| Measure | Description | Time Frame |
|---|---|---|
| BNP | Change from baseline in plasma BNP levels at 24hr, 48hr, 72hr, and 5day | baseline to 24hr, 48hr, 72hr, and 5day |
| ST2 | Change from baseline in plasma ST2 at 24hr, 48hr, 72hr, 5day |
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Inclusion Criteria:
(2) Infusion rates for continuous IV diuretics, inotropes and vasodilators must have been unchanged for at least 2 hours prior to baseline.
5.Left ventricular ejection fraction less than or equal to 35% as assessed using echocardiography, radionuclide ventriculography or contrast angiography within the previous 12 months 6.Dyspnea at rest at both screening and baseline, as assessed by the patient.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lee Su-min | Contact | +82-2-6202-7119 | smlee@yypharm.co.kr |
| Name | Affiliation | Role |
|---|---|---|
| Suck-min Kang, MD.PhD. | Severance Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Severance Hospital | Recruiting | Seoul | South Korea |
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| baseline to 24hr, 48hr, 72hr, and 5day |
| NYHA | New York Heart Association(NYHA) functional classification at 5 days. | baseline to 5day |
| hospitalization | Length of intensive care unit and /or Coronary care unit stay for the index ADHF hospitalization | 31day |
| cardio-renal biomarkers | Change from baseline in cardio-renal biomarkers (Creatinine, BUN, NGAL) at 24hr, 48hr, 72hr and 5day | baseline to 24hr, 48hr, 72hr, and 5day |
| Patient's Global Assessment | Patient's Global Assessment (PGA, 7-likert scale) at 6 hr. : Check rate of patients who responded with Moderate or Marked improvement | 6hr |
| Patients Assessment | Patients Assessment of dyspnea(7-likert scale) at 6hr : Check rate of patients who responded with Moderate or Marked improvement | 6hr |
| re-hospitalization | Time to re-hospitalization due to heart failure after discharge | 30days |
| death. | Time to CV death. | 30days |
| mortality | All cause mortality through 30days | 30days |