Preoperative Levosimendan and Heart Failure (PELS)

Preoperative Levosimendan in Patients With Heart Failure Undergoing Elective Noncardiac Surgery: A Randomized, Placebocontrolled Trial. SIMPLE Study

The purpose of this study is to investigate the safety and efficacy of Levosimendan given preoperative to patients with heart failure undergoing noncardiac surgery.

Study Overview

• Status: Withdrawn
• Conditions: Heart Failure; Hip Fracture
• Intervention / Treatment: Drug: Levosimendan; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Oslo University Hospital - Ullevål
  • Tonsberg, Norway, 3103
    • Vestfold Hospital Trust
• Sweden
  • Gothenburg, Sweden
    • Mölndal Hospital
  • Hudiksvall, Sweden
    • Universitety Hospital Örebro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute surgery. Hip Fracture
• Patient with cardiac failure (EF < 35%) or known coronary disease
• At least 2 of 11 comorbidities
• Patient has to use at least one heart failure medication
• Symptoms of heart failure
• NT-proBNP > 2000pg/ml

Exclusion Criteria:

• < 18 years old
• Participants in other pharmacological study
• Abuse of medicaments or alcohol
• Pregnant or breastfeeding women
• AMI at admission
• HOCM
• Serious aortic stenosis (< 1 cm2)
• Sustained ventricular tachycardia
• Earlier episodes of "torsades de pointes"
• Sustained heartbeat > 120/minute
• Systolic BP < 90 mmHg
• Surgery planned not before 2 hours of study medication can be infused preoperative
• Cardiac surgery
• Dementia
• S-K < 3 mmol/l
• Allergy levosimendan
• Serious liver failure (Known Class C Child-Pugh score)
• Serious kidney failure (GFR < 30 ml/min.)
• Prolonged QTc-interval (male QTc > 0,43 s, female QTc > 0,45 s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Levosimendan	Drug: Levosimendan; At least 2 hours before surgery: Infusion of Levosimendan (0,1 microgram/kg/min.). 24 hours of infusion without a bolus.; Other Names: Simdax; ATC-nr.: C01C X08
PLACEBO_COMPARATOR: Povidon, waterfree etanol, glucosis 5%	Drug: Levosimendan; At least 2 hours before surgery: Infusion of Levosimendan (0,1 microgram/kg/min.). 24 hours of infusion without a bolus.; Other Names: Simdax; ATC-nr.: C01C X08; Drug: Placebo; ml/kg/hours - same infusion rate as active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Heartfailure - Highest NT-proBNP-value the first 7 days after surgery	NT-proBNP 6 hours postoperative, 24 hours postoperative, 48 h postoperative, 72 h postoperative, 96 h postoperative, 120 h postoperative, 144 h postoperative and 168 h postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days of hospitalization		Hospital stay - number of days patients are hospitalized
Use of inotropes (dopamine, Norepinephrine)during postoperative unit stay. Mg/microgram		After 16-18 hours, after 48 hours and every 24 hours if still in the PO-Unit
Mortality	Visits or patients record	30 days
Ischemia	Continous ECG first 24 hours an ECG every second day	7 days postoperative
Myocardial necrosis	Troponin taken every day postoperative	7 days postoperative

Collaborators and Investigators

• Sponsor: Sykehuset i Vestfold HF
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Study Director: Espen Lindholm, MD, Vestfold Hospital trust, Norway; Principal Investigator: Knut A Kirkebøen, PhD, Oslo University Hospital - Ulleval, Norway; Principal Investigator: Mathias Kotyra, Md, Mölndal hospital, Sweden; Principal Investigator: Anders Nydahl, Phd, University Hospital Orebro, Sweden

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): December 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: November 24, 2009
• First Submitted That Met QC Criteria: November 30, 2009
• First Posted (ESTIMATE): December 1, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Fractures, Bone; Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Heart Failure; Hip Fractures; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: SIMPLE