Spanish Randomized Clinical Trial to Compare Levosimendan Versus Placebo in Postoperative Cardiac Surgery (SPARTANS)

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%.

Conditions

• Cardiac Output, Low

Interventions

DRUG

Levosimendan

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.

DRUG

Placebos

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.

Sponsors & Collaborators

• Orion Corporation, Orion Pharma

  collaborator INDUSTRY

• Canary Foundation

  collaborator OTHER

• Dr Negrin Hospital Statistician

  collaborator UNKNOWN

• Dr Negrin Hospital Farmacy

  collaborator UNKNOWN

• CRO TRIDE Asesores SL

  collaborator UNKNOWN

• QBE Europe SA/NV

  collaborator UNKNOWN

• María de los Ángeles Tena Pajuelo

  lead OTHER

Principal Investigators

• Maria Ángeles T Tena Pajuelo, Cardiac surgery · Doctor Negrin University Hospital

• Marta P Perez de Lis Novo, anesthesiology · A Coruña University Complex

• Juan B Bustamante Munguira, Cardiac surgery · Valladolid UNIVERSITY CLINICAL HOSPITAL

• Marc V Vives Santacana, anesthesiology · Doctor Joseh Trueta, Girona university clinical Hospital

• Elisabet B Berastegui Garcia, Cardiac surgery · GERMANS TRIAS I PUJOL DE BADALONA University Hospital

• Pedro M Muñoz Ramirez, anesthesiology · 12 de Octubre University Hospital

• Ana Isabel G Gonzalez Roman, anesthesiology · Puerta del Hierro University Hospital

• Gemma S Sanchez Espin, Cardiac Surgery · Virgen de la Victoria University Hospital

• Emiliano Andres R Rodriguez Caulo, Cardiac Surgery · Virgen Macarena University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-06-17

Primary Completion

2022-01-31

Completion

2022-12-31

Countries

• Spain

Study Locations