Clinical trial NCT00348504: Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support: a Multicentre, Parallel-Group, Randomised, Double-Blind, Double-Dummy Study of Levosimendan Versus Dobutamine in Patients With Acute Heart Failure.
Official title: Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support: a Multicentre, Parallel-Group, Randomised, Double-Blind, Double-Dummy Study of Levosimendan Versus Dobutamine in Patients With Acute Heart Failure.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Heart Failure
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2006-07-04
Enrollment: 1300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to compare the efficacy of levosimendan and dobutamine on all-cause mortality in the 180 days following randomization.


Eligibility criteria: Inclusion Criteria:

* Written, signed and dated informed consent
* Male and female patients over 18 years of age. Females of childbearing potential must have a negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal \[two years since last menstrual cycle\], surgically sterilised or who have undergone a hysterectomy are considered not to be of childbearing potential
* Hospitalised patients with acutely decompensated heart failure
* Left ventricular ejection fraction less than or equal to 30 % as assessed using echocardiography, radionuclide ventriculography or contrast angiography within 12 months
* Clinical need for intravenous inotropic support as evidenced by insufficient response to intravenous diuretics and/or vasodilators (nitroglycerin, nitroprusside) and at least one of the following at screening:

  * oliguria (mean urine output \< 30 ml/h for at least 6 hours) and not a result of hypovolemia
  * dyspnoea at rest or mechanical ventilation for heart failure
  * haemodynamic impairment in those patients with Swan-Ganz catheter inserted (PCWP ≥ 18 mmHg and/or Cardiac Index ≤ 2.2 l/min/m2)

Exclusion Criteria:

* Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy
* Weight ≥ 160 kg
* Cardiac surgery within 30 days before screening
* Stroke within 3 months before screening
* Systolic blood pressure persistently less than 85 mmHg at screening or at baseline
* Heart rate persistently 130 bpm or greater at screening or at baseline
* Serum potassium less than 3.5 mmol/l at screening
* Administration of any inotropic agent (e.g. dobutamine, milrinone, amrinone, enoximone, epinephrine, norepinephrine) except digitalis or dopamine (with dose of less than or equal than 2 mg/kg/min) during the current hospitalisation
* Hypersensitivity to levosimendan or dobutamine or any of their excipients
* A history of Torsades de Pointes
* Severe renal insufficiency (serum creatinine \> 450 mmol/l \[5.0 mg/dl\]) or on dialysis
* Significant hepatic impairment at discretion of the investigator
* Acute bleeding
* Severe anemia (haemoglobin \< 8 g/dl) at screening
* Septicaemia or septic shock
* Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer)
* Participation in a clinical trial with any experimental treatment within 30 days prior to screening or previous participation in the present study
* Administration of levosimendan within 30 days prior to screening

Primary outcomes:
measure: All-cause mortality in the 180 days following randomization.
Secondary outcomes:
measure: All-cause mortality during the 31 days following randomization
measure: Mean change in plasma BNP concentration from baseline to 24 hours after the start of the study drug infusion
measure: Number of day alive and out of hospital (DAOH) during the 180 days following randomization
measure: Patient's evaluation of change in dyspnea at 24 hours following randomization
measure: Patient's evaluation of change in Global Assessment at 24 hours following randomization
measure: Cardiovascular mortality during the 180 days following randomization
Other outcomes:
Locations:
city: Abbott Park
country: United States
facility: Global Medical Information - Abbott
state: Illinois
Study officials:
affiliation: Abbott
name: Robert J Padley, M.D.
role: STUDY_DIRECTOR
References:
citation: Cohen-Solal A, Logeart D, Huang B, Cai D, Nieminen MS, Mebazaa A. Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure. J Am Coll Cardiol. 2009 Jun 23;53(25):2343-8. doi: 10.1016/j.jacc.2009.02.058.
citation: Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M; SURVIVE Investigators. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. doi: 10.1001/jama.297.17.1883.