Effects of Levosimendan in Acute Kidney Injury After Cardiac Surgery (LEVOAKI)

Acute kidney injury (AKI) is a common complication after cardiac surgery. Mismatch in renal oxygen demand-supply may be an important pathogenetic factor. Levosimendan has been shown to improve renal blood flow, glomerular filtration rate and renal oxygenation in healthy controls after cardiac surgery.

In order to investigate the effect of levosimendan in patients with AKI after cardiac surgery, the investigators plan a randomized placebo controlled trial. 30 patients will receive levosimendan or placebo. Renal blood flow and filtration fraction will be measured using infusion clearance technique of para-aminohippuric acid and Chromium ethylenediaminetetraacetic acid (Cr-EDTA) respectively.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Renal Insufficiency, Acute
• Intervention / Treatment: Drug: Levosimendan; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, 41345
    • Department of thoracic anesthesia, Sahlgrenska University Hospital

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:

• Patients in the cardiothoracic intensive care after cardiac surgery with cardiopulmonary bypass
• Acute kidney injury, defined as increase in S-creatinine 50% or 27 mol/L
• Normal S-creatinine before surgery

Exclusion Criteria:

• Ongoing treatment with inotropic drugs (not norepinephrine)
• Central venous oxygen saturation (ScvO2) < 60% despite optimization of hematocrit and volume status
• Need of renal replacement therapy
• Ongoing bleeding
• Patient or next of kin does not consent with study participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Levosimendan; Levosimendan will be given as a loading dose of 12 ug/kg during 30 minutes, and then a continuous infusion of 0,1 ug/kg/min for 180 minutes.	Drug: Levosimendan; Other Names: Simdax
PLACEBO_COMPARATOR: Placebo; Sodium chloride will be given as a loading dose during 30 minutes and then a continuous infusion for 180 minutes at a rate mimicking the levosimendan group above.	Drug: Placebo; Sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal blood flow	Renal blood flow will be measured using infusion clearance technique of para-aminohippuric acid. Measurements will be made in duplicates before and after administration of the study drug.	5 Hours
Glomerular filtration rate	Filtration fraction will be determined using be measured using infusion clearance technique of Chromium ethylenediaminetetraacetic acid (Cr-EDTA). Measurements will be made in duplicates before and after administration of the study drug. Glomerular filtration rate will be calculated as the filtration fraction multiplied by renal plasma flow.	5 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine	Measurement of serum creatinine will be made daily the first 4 days after the study	4 days

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Investigators: Study Director: Sven-Erik Ricksten, Professor, Sahlgrenska Academy, dept of clinical science

Publications and helpful links

General Publications

• Bragadottir G, Redfors B, Ricksten SE. Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study. Crit Care Med. 2013 Oct;41(10):2328-35. doi: 10.1097/CCM.0b013e31828e946a.
• Tholen M, Ricksten SE, Lannemyr L. Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study. Crit Care. 2021 Jun 12;25(1):207. doi: 10.1186/s13054-021-03628-z.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): December 1, 2020
• Study Completion (ACTUAL): December 1, 2020

Study Registration Dates

• First Submitted: August 20, 2015
• First Submitted That Met QC Criteria: August 20, 2015
• First Posted (ESTIMATE): August 24, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: cardiac surgery; acute kidney injury; levosimendan; renal blood flow
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Wounds and Injuries; Renal Insufficiency; Acute Kidney Injury; 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: SahlgrenskaUHThoraxLL3