Efficacy and Safety of Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients.
Information source: Orion Corporation, Orion Pharma
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heart Failure
Intervention: Levosimendan (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Orion Corporation, Orion Pharma Official(s) and/or principal investigator(s): Claes-HÃ¥kan Bergh, Assoc Prof, Principal Investigator, Affiliation: Institution of Cardiology, Sahlgrenska University Hospital, Sweden
Summary
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.
Clinical Details
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.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Compare the hemodynamic parameters Cardiac Index (CI) and Pulmonary Capillary Wedge Pressure (PCWP) from baseline to 24 hours, between the two groups.
Secondary outcome: 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.
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Cardiology Department, Sahlgrenska University Hospital, Gothenburg 413 45, Sweden
Additional Information
Related publications: Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, Harjola VP, Mitrovic V, Abdalla M, Sandell EP, Lehtonen L; Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002 Jul 20;360(9328):196-202.
Starting date: November 2002
Last updated: September 21, 2005
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