Coronary Artery Bypass GraftingPhase 3LICORNNCT02184819
Preoperative Levosimendan in CABG Patients With Poor LV Function
A Phase 3 study testing levosimendan in people with Coronary Artery Bypass Grafting and Left Ventricular Dysfonction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The investigators want to test the hypothesis that an infusion of levosimendan started prior to CABG surgery can reduce incidence and severity of low cardiac output syndrome in patients with poor LV function (EF 40% or less). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Bypass Grafting, Left Ventricular Dysfonction
- What is being tested?
- levosimendan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 335 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2013to Nov 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 Years and older
- scheduled for CABG with CPB
- with or without asociated cardiac repair
- ejection fraction less than 40%
- signed informed consent
Who cannot join
- preoperative renal failure (creatinine clearance less than 30 ml/min)
- liver failure (prothrombine time less than 50% in the absence of vitamin K antagonist)
- cardiac surgery without CABG
- pregnancy
- emergency surgery
- known allergy to levosimendan
Show all 11Show fewer
- severe hypotension prior to surgery
- severe tachycardia
- prior history of torsade de pointe
- dynamic obstruction od left ventricular outflow tract
- lack of signed informed consent.
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France
Paris, 75015
About this study
Official title: Effects of Levosimendan Pretreatment in Patients With Low Ejection Fraction (40 % or Less) Undergoing CABG: a Randomised, Double Blind, Multicenter Trial
The investigators want to test the hypothesis that an infusion of levosimendan started prior to CABG surgery can reduce incidence and severity of low cardiac output syndrome in patients with poor LV function (EF 40% or less).
Read the detailed description
Background: Patients with an ejection fraction of less than 40% are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite the use of potent inotropic agents or even ventricular mechanical assist devices, the mortality rate of such patients remains very high (from 17 to 38%). Their hospital stay is also prolonged and the cost of care for this population is increased. Two studies have suggested that post-operative administration of levosimendan could reduce hospital length of stay and long term (Day180) mortality in patients with LCOS. In addition a few studies have also suggested that pre-operative infusion of levosimendan (pre-conditioning) could reduce the use of other inotropes and mechanical assist devices in patients at high risk of developing LCOS. Unfortunately, the data supporting the beneficial effects of levosimendan in high risk cardiac surgery patients is very limited. Main goal: To evaluate the efficacy of a pre-operative infusion of levosimendan in high risk patients (EF less than 40%) undergoing cardiac surgery (CABG or combined surgery: CABG and valve replacement) to improve outcome. Secondary goals: To evaluate: 1) the clinical safety of a pre-operative infusion of levosimendan, 2) the costs of care in the levosimendan and control groups. Experimental setup: Prospective, multicenter, randomized versus placebo, double-blind trial. Treatment modalities: levosimendan will be administered by the intravenous route, according to a continuous infusion of 0.1mcg/kg/min over 24 hours. Levosimendan infusion (0.1mcg/kg/min) will be started immediately after induction of anaesthesia. The delay between infusion start and skin incision can be estimated between 30 to 60 min. The investigators decided to skip the bolus infusion that is frequently associated with systemic hypotension, which may result in serious adverse events and protocol exclusion. Study duration and patient follow-up: Patients will be recruited over 23 months. Individual follow-up will last 6 months. Overall duration of study will be 29 months.
- Being tested
- levosimendan, Placebo
- Keywords
- coronary artery bypass graft, left ventricular dysfunction, low cardiac output syndrome, levosimendan, mortality, inotropic agents, cardiac mechanical assist devices, renal replacement therapy, mechanical ventilation duration, ICU stay
- Medical subject headings
- Ventricular Dysfunction, Left, Cardiac Output, Low
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levosimendanDrug
Also called Simdax
24 hour continuous infusion at the rate of 0,1 µg/kg/min
PlaceboDrug
Also called riboflavine
24 hour infusion at a rate of 0,1 µg/kg/min assuming that it contains study drug
| Study group | Role | What they receive |
|---|---|---|
| levosimendan | Active comparator | study drug Receives: Drug: levosimendan |
| placebo | Placebo comparator | placebo group Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed low cardiac output syndrome
Composite of the three following items:the need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion; the need for post-operative mechanical assist devices (intra-aortic balloon pump: IABP, extra-corporeal life support: ECLS) or failure to wean from these techniques if they were inserted pre-operatively; the need for renal replacement therapy during ICU stay
Measured: within the 28 days after ICU admission
Secondary outcomes (4)
mortality at Day 28 and Day 180
Measured: 180 postoperative days
The need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion
Measured: 1 time during 24h beyond operative
The description of renal replacement therapy during ICU stay
renal failure requiring renal replacement therapy may occur anytime within 12 hours following surgery and may last 1-2 weeks on average.
Measured: within the 28 days after ICU admission
number of ventilator-free days and out-of-ICU days at Day 28.
Measured: 28 postoperative days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2014 (estimated)
- Study startJun 2013
- Primary completionJun 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery Bypass GraftingStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 335 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Bernard Cholley, MD, PhD, Principal investigator, Anesthesiology and Intensive Care, Hopital Européen Georges Pompidou, Paris, FranceThibaut Caruba, PharmD, Principal investigator, Pharmacy department, Hopital Européen Georges Pompidou, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02184819
- Sponsor's protocol ID
- P110138
- Acronym
- LICORN
- Status last verified
- Nov 2015
- First submitted
- 23 Oct 2013
- Last updated
- 25 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Levin R, Degrange M, Del Mazo C, Tanus E, Porcile R. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol. 2012 Sep;17(3):125-30.
PubMed 23620700De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg. 2007 Apr;104(4):766-73. doi: 10.1213/01.ane.0000256863.92050.d3.
PubMed 17377079Tritapepe L, De Santis V, Vitale D, Santulli M, Morelli A, Nofroni I, Puddu PE, Singer M, Pietropaoli P. Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study. Br J Anaesth. 2006 Jun;96(6):694-700. doi: 10.1093/bja/ael082. Epub 2006 Apr 4.
PubMed 16595616Cholley B, Caruba T, Grosjean S, Amour J, Ouattara A, Villacorta J, Miguet B, Guinet P, Levy F, Squara P, Ait Hamou N, Carillion A, Boyer J, Boughenou MF, Rosier S, Robin E, Radutoiu M, Durand M, Guidon C, Desebbe O, Charles-Nelson A, Menasche P, Rozec B, Girard C, Fellahi JL, Pirracchio R, Chatellier G; -. Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):548-556. doi: 10.1001/jama.2017.9973.
PubMed 28787507Caruba T, Hourton D, Sabatier B, Rousseau D, Tibi A, Hoffart-Jourdain C, Souag A, Freitas N, Yjjou M, Almeida C, Gomes N, Aucouturier P, Djadi-Prat J, Menasche P, Chatellier G, Cholley B. Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (</=40 %) undergoing CABG with cardiopulmonary bypass (LICORN study). J Cardiothorac Surg. 2016 Aug 5;11(1):127. doi: 10.1186/s13019-016-0530-z.
PubMed 27496105
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Levosimendan Pretreatment in Patients With Low Ejection Fraction (40 % or Less) Undergoing CABG: a Randomised, Double Blind, Multicenter Trial
- ClinicalTrials.gov ID
- NCT02184819
- Acronym / sponsor ID
- LICORN / P110138
- Keywords
- coronary artery bypass graft, left ventricular dysfunction, low cardiac output syndrome, levosimendan, mortality, inotropic agents, cardiac mechanical assist devices, renal replacement therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 335 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- Jun 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 9 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators want to test the hypothesis that an infusion of levosimendan started prior to CABG surgery can reduce incidence and severity of low cardiac output syndrome in patients with poor LV function (EF 40% or less).
Detailed description
Background: Patients with an ejection fraction of less than 40% are at high risk of developing postoperative low cardiac output syndrome (LCOS). Despite the use of potent inotropic agents or even ventricular mechanical assist devices, the mortality rate of such patients remains very high (from 17 to 38%). Their hospital stay is also prolonged and the cost of care for this population is increased. Two studies have suggested that post-operative administration of levosimendan could reduce hospital length of stay and long term (Day180) mortality in patients with LCOS. In addition a few studies have also suggested that pre-operative infusion of levosimendan (pre-conditioning) could reduce the use of other inotropes and mechanical assist devices in patients at high risk of developing LCOS. Unfortunately, the data supporting the beneficial effects of levosimendan in high risk cardiac surgery patients is very limited. Main goal: To evaluate the efficacy of a pre-operative infusion of levosimendan in high risk patients (EF less than 40%) undergoing cardiac surgery (CABG or combined surgery: CABG and valve replacement) to improve outcome. Secondary goals: To evaluate: 1) the clinical safety of a pre-operative infusion of levosimendan, 2) the costs of care in the levosimendan and control groups. Experimental setup: Prospective, multicenter, randomized versus placebo, double-blind trial. Treatment modalities: levosimendan will be administered by the intravenous route, according to a continuous infusion of 0.1mcg/kg/min over 24 hours. Levosimendan infusion (0.1mcg/kg/min) will be started immediately after induction of anaesthesia. The delay between infusion start and skin incision can be estimated between 30 to 60 min. The investigators decided to skip the bolus infusion that is frequently associated with systemic hypotension, which may result in serious adverse events and protocol exclusion. Study duration and patient follow-up: Patients will be recruited over 23 months. Individual follow-up will last 6 months. Overall duration of study will be 29 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| levosimendan | Active comparator | Drug: levosimendanstudy drug |
| placebo | Placebo comparator | Drug: Placeboplacebo group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18 Years and older
- scheduled for CABG with CPB
- with or without asociated cardiac repair
- ejection fraction less than 40%
- signed informed consent
Key exclusion criteria (11 listed)
- preoperative renal failure (creatinine clearance less than 30 ml/min)
- liver failure (prothrombine time less than 50% in the absence of vitamin K antagonist)
- cardiac surgery without CABG
- pregnancy
- emergency surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| levosimendanAlso: Simdax24 hour continuous infusion at the rate of 0,1 µg/kg/min | Drug | levosimendan |
| PlaceboAlso: riboflavine24 hour infusion at a rate of 0,1 µg/kg/min assuming that it contains study drug | Drug | placebo |
Primary outcome
Confirmed low cardiac output syndrome
Time frame: within the 28 days after ICU admission
Composite of the three following items:the need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion; the need for post-operative mechanical assist devices (intra-aortic balloon pump: IABP, extra-corporeal life support: ECLS) or failure to wean from these techniques if they were inserted pre-operatively; the need for renal replacement therapy during ICU stay
4 secondary outcomes
mortality at Day 28 and Day 180
Time frame: 180 postoperative days
The need for inotropic agents beyond 24 hours following the end of levosimendan/placebo infusion
Time frame: 1 time during 24h beyond operative
The description of renal replacement therapy during ICU stay
Time frame: within the 28 days after ICU admission
number of ventilator-free days and out-of-ICU days at Day 28.
Time frame: 28 postoperative days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2016.
- Background: PubMed 23620700Levin R, Degrange M, Del Mazo C, Tanus E, Porcile R. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol. 2012 Sep;17(3):125-30.
- Background: PubMed 17377079De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg. 2007 Apr;104(4):766-73. doi: 10.1213/01.ane.0000256863.92050.d3.
- Background: PubMed 16595616Tritapepe L, De Santis V, Vitale D, Santulli M, Morelli A, Nofroni I, Puddu PE, Singer M, Pietropaoli P. Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study. Br J Anaesth. 2006 Jun;96(6):694-700. doi: 10.1093/bja/ael082. Epub 2006 Apr 4.
- Derived from this study: PubMed 28787507Cholley B, Caruba T, Grosjean S, Amour J, Ouattara A, Villacorta J, Miguet B, Guinet P, Levy F, Squara P, Ait Hamou N, Carillion A, Boyer J, Boughenou MF, Rosier S, Robin E, Radutoiu M, Durand M, Guidon C, Desebbe O, Charles-Nelson A, Menasche P, Rozec B, Girard C, Fellahi JL, Pirracchio R, Chatellier G; -. Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):548-556. doi: 10.1001/jama.2017.9973.
- Derived from this study: PubMed 27496105Caruba T, Hourton D, Sabatier B, Rousseau D, Tibi A, Hoffart-Jourdain C, Souag A, Freitas N, Yjjou M, Almeida C, Gomes N, Aucouturier P, Djadi-Prat J, Menasche P, Chatellier G, Cholley B. Rationale and design of the multicenter randomized trial investigating the effects of levosimendan pretreatment in patients with low ejection fraction (</=40 %) undergoing CABG with cardiopulmonary bypass (LICORN study). J Cardiothorac Surg. 2016 Aug 5;11(1):127. doi: 10.1186/s13019-016-0530-z.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernard Cholley, MD, PhD principal investigator
Anesthesiology and Intensive Care, Hopital Européen Georges Pompidou, Paris, France
Thibaut Caruba, PharmD principal investigator
Pharmacy department, Hopital Européen Georges Pompidou, Paris, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing levosimendan in people with Coronary Artery Bypass Grafting and Left Ventricular Dysfonction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed low cardiac output syndrome (time frame: within the 28 days after ICU admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02184819, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2016.