Spanish Randomized Clinical Trial to Compare Levosimendan Versus Placebo in Postoperative Cardiac Surgery (SPARTANS)
SPARTANS
Rationale and Design of a Multicenter Randomized Trial of Levosimendan to Reduce Low Cardiac Output Syndrome in Low Ejection Fraction (≤ 35%) Cardiac Surgery Patients. Spanish Randomized Clinical Trial on Levosimendan (SPARTANS Study)
2 other identifiers
interventional
300
1 country
9
Brief Summary
Low cardiac output Syndrome (LCOS) is a complication that appears in approximately 20% of cardiac surgeries with extracorporeal circulation. LCOS is associated with increased mortality, delayed recovery and prolonged hospital stay. The Spanish Randomized Clinical Trial on Levosimendan (brand name: Sindax) (SPARTANS) aims to demonstrate the effectiveness of the preoperative use of Levosimendan in reducing LCOS in patients with poor left ventricle ejection fraction (LVEF) undergoing elective cardiac surgery. SPARTANS study is a multicenter, randomized triple-blind, placebo-controlled trial. 300 patients with LVEF ≤ 35%, undergoing elective cardiac surgery will be recruited from 9 Spanish hospitals and randomized into two groups: Preoperative administration of levosimendan or placebo for 24 hours. The study drug will be started as a continuous infusion (0.1 µg/kg/min) at least 8 hours before surgery to complete 24h duration. The primary endpoint will be 30-day LCOS. It will be evaluated using any of the following criteria: 1\) postoperated cardiac index ≤2.0 L / min / m2, 2) a need to implant a intra-aortic balloon pump/ left ventricular assist device, 3) a vasoactive inotropic scale (VIS) \> 5.5. The secondary end-point will be composite event rate at one year including any of the following events: death from any cause, need for renal replacement therapy or dialysis and LCOS. The sample size is based on the assumption that levosimendan reduces LCOS by 50% being necessary a sample size of 300 patients to carry out the study. The Research Team of each hospital, will carry out the clinical follow-up by telephone or clinical interview of the patient according to the time intervals: 30 days and 1 year. We estimate that the total sample size of 300 patients will be reached in 2-2.5 years. In conclusion, the effectiveness of levosimendan has not yet been reported with a good evidence in cardiac surgery. The purpose of the "Spanish Randomized Clinical Trial on Sindax" (SPARTANS) trial is to evaluate the beneficial effect of preoperative use of levosimendan compared with placebo to reduce perioperative LCOS in patients undergoing cardiac surgery with poor LVEF ≤ 35%.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2020
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 11, 2019
CompletedFirst Posted
Study publicly available on registry
November 27, 2019
CompletedStudy Start
First participant enrolled
June 17, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2022
CompletedJuly 24, 2020
November 1, 2019
1.5 years
November 11, 2019
July 22, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of Participants with LCOS
LCOS will be considered if: 1\) Postoperated cardiac index ≤2.0 L / min / m2 (liters / minute / square meter)
up to 30 days of cardiac surgery
Number of Participants with LCOS
LCOS will be considered if: 2\) The need to implant an intra-aortic balloon pump
up to 30 days of cardiac surgery
Number of Participants with LCOS
LCOS will be considered if: 3\) The need to implant a left ventricular assistance device
up to 30 days of cardiac surgery
Number of Participants with LCOS
LCOS will be considered if: 4\) To have a vasoactive inotropic scale (VIS) \> 5.5 Vasoactive inotropic scale will be measured following the following formula: inotropic scale (IS) + 10 x Milrinone (μg / kg / min) + 100 x norepinephrine (μg / kg / min) + 10000 × vasopressin (U / kg / min). The inotropic scale (SI) will be calculated using the following formula: Dopamine (μg / kg / min) + Dobutamine (μg / kg / min) + 100 × adrenaline (μg / kg / min).
up to 30 days of cardiac surgery
Secondary Outcomes (3)
Composite event rate
up to one year after surgery
Composite event rate
up to one year after surgery
Composite event rate
up to one year after surgery
Other Outcomes (5)
Number of Patients with need for renal replacement therapy or dialysis
up to 30 days
Intensive Care Unit stay
until discharge from Intensive Care Unit
Total post-surgical stay
until discharge from hospital
- +2 more other outcomes
Study Arms (2)
Levosimemdam
EXPERIMENTALLevosimendan 2.5 mg / ml concentrate for solution for infusion. A 5 ml vial contains 12.5 mg of levosimendan. The concentrate is a clear solution, yellow or orange, for dilution before administration. The study drug infusion will start one day before surgery in an Intensive Care Unit with at least 8 hours of administration before surgery. A continuous infusion at 0.1 µg/kg/min will be administered to complete 24h duration.
Placebo
PLACEBO COMPARATORPatients in the placebo group will receive a water-soluble vitamin B2 concentrate with 0.4 mg / ml sodium riboflavin phosphate to obtain the same color as the preparation of levosimendan and ethanol anhydrous 100 mg / ml to resemble the levosimendan odor, which will be administered at the same levosimendan infusion rate.
Interventions
Levosimendan SIMDAX 2.5 mg / ml concentrate for solution for infusion. The concentrate is a clear solution, yellow or orange, for dilution before administration. A 5 ml vial contains 12.5 mg of levosimendan. The study drug infusion will start one day before surgery in an Intensive Care Unit with at least 8 hours of administration before surgery. A continuous infusion at 0.1 µg/kg/min will be administered to complete 24h duration.
Patients in the placebo group will receive a water-soluble vitamin B2 concentrate with 0.4 mg / ml sodium riboflavin phosphate to obtain the same color as the preparation of levosimendan and ethanol anhydrous 100 mg / ml to resemble the levosimendan odor, which will be administered at the same levosimendan infusion rate.
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years
- Written informed consent
- LVEF ≤35% detected by echocardiography carried out at least one week before surgery.
- Scheduled AVR or/and Scheduled CABG with CBP.
You may not qualify if:
- Previous levosimendan administration.
- Emergency operation.
- Kidney or liver trasplant or awaiting it.
- Hepatic cirrhosis Child C. In case Child B, contact coordinating center.
- Any degree of preoperative right ventricular failure.
- Preoperative creatinine \> 2 mg / dl.
- Valve desease other than aortic.
- Renal failure requering dialysis (or creatinine clearance \< 30ml / min).
- Hemodynamic instability (need for inotropics, unstable angina, acute myocardial infarction, intra-aortic balloon pump).
- Patients underwent previous cardiac surgery.
- Allergy or hypersensitivity to levosimendan or any of its excipients
- Severe hypotension (sistolic arterial tension \< 80 mmHg or mean arterial pressure \<50 mmHg ) and tachycardia ( heart rate \>130 bpm).
- History of Torsades de Pointes.
- Pregnancy or breast-feeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- María de los Ángeles Tena Pajuelolead
- Orion Corporation, Orion Pharmacollaborator
- Canary Foundationcollaborator
- Dr Negrin Hospital Statisticiancollaborator
- Dr Negrin Hospital Farmacycollaborator
- CRO TRIDE Asesores SLcollaborator
- QBE Europe SA/NVcollaborator
Study Sites (9)
GERMANS TRIAS I PUJOL DE BADALONA university Hospital
Badalona, Barcelona, 08916, Spain
Doctor Josep Trueta university Hospital
Girona, Gerona, 17007, Spain
Doctor Negrin University Hospital
Las Palmas de Gran Canaria, Gran Canarias, 35010, Spain
Puerta del Hierro University Hospital
Majadahonda, Madrid, 28222, Spain
Virgen de la Victoria University Hospital
Málaga, Malaga, 29010, Spain
A coruña UNIVERSITY HOSPITAL COMPLEX A CORUÑA
A Coruña, 15006, Spain
12 de Octubre University Hospital
Madrid, 28041, Spain
Virgen Macarena University Hospital
Seville, 410019, Spain
Valladolid universitary Hospital
Valladolid, 47003, Spain
Related Publications (4)
Tena MA, Urso S, Gonzalez JM, Santana L, Sadaba R, Juarez P, Gonzalez L, Portela F. Levosimendan versus placebo in cardiac surgery: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg. 2018 Nov 1;27(5):677-685. doi: 10.1093/icvts/ivy133.
PMID: 29718383RESULTLandoni G, Mizzi A, Biondi-Zoccai G, Bruno G, Bignami E, Corno L, Zambon M, Gerli C, Zangrillo A. Reducing mortality in cardiac surgery with levosimendan: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth. 2010 Feb;24(1):51-7. doi: 10.1053/j.jvca.2009.05.031. Epub 2009 Aug 22.
PMID: 19700350RESULTNiu ZZ, Wu SM, Sun WY, Hou WM, Chi YF. Perioperative levosimendan therapy is associated with a lower incidence of acute kidney injury after cardiac surgery: a meta-analysis. J Cardiovasc Pharmacol. 2014 Feb;63(2):107-12. doi: 10.1097/FJC.0000000000000028.
PMID: 24126568RESULTLevin 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.
PMID: 23620700RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maria Ángeles T Tena Pajuelo, Cardiac surgery
Doctor Negrin University Hospital
- PRINCIPAL INVESTIGATOR
Marta P Perez de Lis Novo, anesthesiology
A Coruña University Complex
- PRINCIPAL INVESTIGATOR
Juan B Bustamante Munguira, Cardiac surgery
Valladolid UNIVERSITY CLINICAL HOSPITAL
- PRINCIPAL INVESTIGATOR
Marc V Vives Santacana, anesthesiology
Doctor Joseh Trueta, Girona university clinical Hospital
- PRINCIPAL INVESTIGATOR
Elisabet B Berastegui Garcia, Cardiac surgery
GERMANS TRIAS I PUJOL DE BADALONA University Hospital
- PRINCIPAL INVESTIGATOR
Pedro M Muñoz Ramirez, anesthesiology
12 de Octubre University Hospital
- PRINCIPAL INVESTIGATOR
Ana Isabel G Gonzalez Roman, anesthesiology
Puerta del Hierro University Hospital
- PRINCIPAL INVESTIGATOR
Gemma S Sanchez Espin, Cardiac Surgery
Virgen de la Victoria University Hospital
- PRINCIPAL INVESTIGATOR
Emiliano Andres R Rodriguez Caulo, Cardiac Surgery
Virgen Macarena University Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Researches will use a computer-generated permuted block randomization established by an independent Statistician. Pharmacy of each hospital will prepare randomized treatment, without being involved in the trial. Patients and physicians will be blind to the randomized therapeutic strategy that each patient will receive. The data will be entered into a specific electronic database in an anonymized and dissociated manner.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Cardiac Surgeon
Study Record Dates
First Submitted
November 11, 2019
First Posted
November 27, 2019
Study Start
June 17, 2020
Primary Completion
January 1, 2022
Study Completion
December 1, 2022
Last Updated
July 24, 2020
Record last verified: 2019-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- From the fourth year of the study and they will be available indefinitely where it is published.
Once the statistical analysis is completed during third year, the results of the study will be presented at the Congresses of the Spanish Society of Cardiothoracic Surgery. The informs and conclusions obtained by the statistical analysis of the study population will be sent for publication in impact journals. We will share all IPD that underlie results in a publication.