Efficacy and Safety of Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients.

This study has been completed.
Sponsor:
Information provided by:
Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier:
NCT00219388
First received: September 14, 2005
Last updated: September 21, 2005
Last verified: September 2005
  Purpose

The purpose of this study is to compare the effects of levosimendan with dobutamine on heart function in patients suffering of severe chronic heart failure.


Condition Intervention Phase
Heart Failure
Drug: Levosimendan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Short-Term Intravenous Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients Treated With Beta-Receptor Blocking Agents.

Resource links provided by NLM:


Further study details as provided by Orion Corporation, Orion Pharma:

Primary Outcome Measures:
  • Compare the hemodynamic parameters Cardiac Index (CI) and Pulmonary Capillary Wedge Pressure (PCWP) from baseline to 24 hours, between the two groups.

Secondary Outcome Measures:
  • Compare the efficacy and safety between the treatment groups, with regard to:
  • • Changes in hemodynamic parameters from baseline to 24 and 48 hours.
  • • Change in study subject’s and investigator’s assessment of symptoms of heart failure at 48 hours and 1-month follow-up.
  • • Change in New York Heart Association (NYHA) classat 48 hours and 1-month follow-up.
  • • Ability to continue treatment with β-receptor blocking agents.
  • • Days alive and out of hospital during the 1-month follow-up period.
  • • Change in B-type Natriuretic Polypeptide (BNP)at 24 and 48 hours and 1-month follow-up.
  • • Proportion of treatment discontinuations and/or need for rescue therapy due to lack of efficacy.

Estimated Enrollment: 60
Study Start Date: November 2002
Estimated Study Completion Date: April 2005
Detailed Description:

Patients with decompensate heart failure (NYHA III-IV) and in need of intravenous inotrop support and who fulfil all inclusion and no exclusion criteria will be randomised into the study in proportion 1:1. Although stratification will be done so patients treated with beta-receptor blocker carvedilol will be divided the same between the study groups.

All patients will receive infusions in parallell, one of the groups will receive active product (levosimendan or dobutamine) and the other will receive placebo (double-dummy technique).

Catheterisation for measurement of hemodynamic parameters will be performed according to routine methods at the clinic. The measurements of the hemodynamic variables will start 30 minutes before start of study drug infusion and will be finished 48 hours after start of infusion. The most important variables during the measurements is Cardiac Index (CI)and Pulmonary Capillary Wedge Pressure (PCWP).

Parallel registration will be done on ECG, blood pressure, blood frequency, central venous pressure, and lung artery pressure. Heart failure and other clinical symptoms will be registered continuously during 48 hours. Blood samples will be taken intermittent to record the blood values. Cogent rules for decreasing/increasing of the dose can be found in the study protocol, likewise rules for interruption or stoop for infusion.

Registration of side-effects will be done continuously. The recommendation for treatment for known side effects could be found in the protocol (section 5.3.4) and the protocol should be available during the study procedure.

One month after the study the patients will be followed up with a very careful examination and also of the amount of visits and reason for visits to hospital during the past 30-35 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Decompensated chronic heart failure of ischemic or non-ischemic origin, in NYHA class III to IV, despite optimised conventional treatment and who may benefit from intravenous positive inotropic agents as per the investigator’s judgment.
  • Ongoing treatment with a beta-receptor blocking agent in a stable regimen for at least 3 months and at an optimal dose as per the investigator’s judgment.
  • Left ventricular (LV) ejection fraction (EF) less than or similar to 35%.
  • CI < 2.5 l/min/m2.
  • Mean PCWP >15 mmHg.

Main Exclusion Criteria:

  • Significant mechanical obstruction affecting ventricular filling and/or outflow.
  • Systolic blood pressure 85 mmHg or less at screening and/or baseline.
  • Heart rate 130 bpm or greater, persistent for at least 5 minutes at screening and/or baseline.
  • Severe angina pectoris during the 6 hours before screening and/or baseline.
  • Deterioration of chronic heart failure due to an acute myocardial infarction within 5 days before screening measurements.
  • Administration of Simdax within 1 month before baseline.
  • A history of Torsades de Pointes.
  • Evidence of severe renal insufficiency (serum creatinine > 450 μmol/l or on dialysis) at screening.
  • Significant hepatic impairment or elevation of liver enzymes to 5 times the upper limit of normal range of the analysing laboratory at screening.
  • Acute bleeding or severe anaemia.
  • Heart surgery within 3 months before baseline.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00219388

Locations
Sweden
Cardiology Department, Sahlgrenska University Hospital
Gothenburg, Sweden, 413 45
Sponsors and Collaborators
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Claes-Håkan Bergh, Assoc Prof Institution of Cardiology, Sahlgrenska University Hospital, Sweden
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00219388     History of Changes
Other Study ID Numbers: 3001075, Sponsor: Orion Pharma
Study First Received: September 14, 2005
Last Updated: September 21, 2005
Health Authority: Sweden: Swedish National Council on Medical Ethics

Keywords provided by Orion Corporation, Orion Pharma:
Safety
Efficacy
Levosimendan
Dobutamine
Intravenous
Invasive hemodynamics
Decompensated Heart Failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Simendan
Dobutamine
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anti-Arrhythmia Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Vasodilator Agents

ClinicalTrials.gov processed this record on July 24, 2014