SIRAKI 02 Posthoc Analysis.

NCT06781294 | Active Not Recruiting DMC

• 1 other identifier: SIRAKI02POSTHOC
• Study Type: interventional
• Target: 343
• Locations: 1 country
• Sites: 1

Brief Summary

Our randomized controlled trial with 343 patients requiring non emergent cardiac surgery with a prolonged expected cardiopulmonary bypass (CPB) time (\>90 minutes) demonstrated that the use of an extracorporeal blood purification (EBP) device (oXiris) connected to the CPB circuit during all surgery was associated with a decrease in the incidence of CSA-AKI within the first 7 days from surgery (nearly 12% reduction). The study was conducted in two university centres of the Barcelona metropolitan area between 2016 and 2022, randomising 343 patients (1:1) to receive either an EBP device connected to the CPB circuit or a standard strategy with CPB alone. First of all the rate of acute kidney disease (AKD) and chronic kidney disease (CKD) in the sutdy population has not been reported and we will analyse if there were differences between groups as other studies have suggested with different interventions. Concerning the intervention safety, no differences were observed in terms of intraoperative blood products (red blood cells, plasma and platelets) requirements between both groups. In order to improve knowledge about the safety of the technique it is very important to ensure that antibiotics levels in plasma during the time the adsorption device is connected to CPB, are not being modified by the intervention. Antibiotic prophylaxis during cardiac surgery is one of the cornerstones and has proved to effectively reduce perioperative infection especially concerning valve replacement procedures. In this sense, our two centres use the same strategy with cephalosporins (Cefazolin in Germans Trias Hospital and Cefuroxime in Bellvitge Hospital) with an early administration at the operating room (OR) before connecting patient to CPB and a late dose after removing CPB (3 hours after the first dose). We know from previous reports that the use of antibiotics during CRRT with oXiris is safe and normally does not require dose adjustments although no reports have been made of its use connected to CPB and antibiotics dosing. Completing the safety issues, heparin and protamine doses during surgery have been registered in the patient's electronic history and should be checked and transferred to a database that allows to adequately analyse potential differences between groups. Other studies performed in cardiac surgery with adsorption devices have reported safety issues with platelets consumption and heparin requirements during surgery. In our protocol, heparin was administered prior to CPB initiation either based on the patient's weight or using hemostasis management system (HMS) plus technology in order to minimise overdosing. Heparin was administered during all CPB time in order to maintain activated clotting time (ACT) over 500 seconds and based on HMS plus technology. Protamine for heparin reversal at CPB withdrawal was administered using both methods too. Protamine administration can be associated with hypotensive episodes. In our study, the decrease in CSA-AKI within the first 7 days from surgery achieved with the use of EBP connected to the CPB was more significant in CKD, DM, Low LVEF, Hypertension and non-obese patients. Whether this effect can be partially explained by the mild cytokines concentration differences observed in IL-8 and TNF-a at T1 (after removing clamp from surgery) and T2 (at ICU admission) has still not been evaluated. This reduction of inflammatory response syndrome (SIRS) during CPB time that could be related with the use of adsorption devices, should be also translated into a decrease of catecholamines and probably insulin requirements during surgery. A noteworthy point to consider is that although the use of propofol has been extended in cardiac surgery, little is known about the potential antiinflammatory effect it may have in patients. It is important to identify those patients who received propofol to control this potential bias in terms of antiinflammatory effect. Besides this objective it is also very important to ensure that no adsorption of propofol took place with the use of EBP, as previous studies have reported higher requirements of sedation drugs with the use of CRRT or other devices with adsorption properties. Finally, nearly 25% of the patients in the EBP group received ultrafiltration with doses that vary from 200 mL up to 3000 mL. We know from previous trials that ultrafiltration is clearly related with the removal of middle weight molecules which is presumably beneficial for patients with SIRS but that in specific scenarios this effect could be even detrimental for some patients. Whether the ultrafiltration performed in our study may have an effect in antibiotics, heparin, protamine, catecholamines, insulin or even propofol should be elucidated in order to settle the idoneous modality in which EBP should be performed when connected to CPB during cardiac surgery. All these outcomes will be assessed controled by gender and age.

Conditions

Cardiac Surgery Requiring Cardiopulmonary Bypass; Acute Kidney Injury; Chronic Kidney Disease(CKD); Kidney Failure, Acute

Keywords

cytokines; heparin; protamine; propofol; vasopressors; insulin; Acute kidney disease; chronic kidney disease; renal recovery; extracorporeal blood purification; hemadsorption; oXiris; cardiopulmonary bypass; cardiac surgery; acute kidney injury

Outcome Measures

Primary Outcomes (1)

• Cytokines differences in subgroups

  Cytokine differences (IL-2, IL-6, IL-8, IL-10, TNF-a, and INF-y) between intervention and standard care in subgroups (CKD, Low LVEF, DM, Hypertension and non-obese population). Determination of cytokines was done at baseline (T0), end of CPB (T1), ICU admission (T2), and 24 hours after surgery (T3). Variations of these cytokines levels (especially during CPB T1-T0) will be analysed in subgroups where the intervention with the EBP device seemed to be more effective.

  24 hours

Secondary Outcomes (14)

• Intraoperatory antibiotic concentrations.

  During surgery

• Heparin administration

  During surgery

• Protamine administration.

  During surgery

• Insulin subcutaneous administration.

  During surgery

• Vasopressor administration (Norepinephrine).

  During surgery

Study Arms (2)

INTERVENTION

ACTIVE COMPARATOR

Extracorporeal blood purification device connected to cardiopulmonary bypass.

Device: Extracorporeal Cytokine hemadsorption therapy

CONTROL

NO INTERVENTION

Standard of care during cardiopulmonary bypass (includes ultrafiltration with polysulphone if required)

Interventions

Extracorporeal Cytokine hemadsorption therapy DEVICE

Extracorporeal blood purification with oXiris set connected to cardiopulmonary bypass during all CPB time. Ultrafiltration was permitted.

Also known as: oXiris, Extracorporeal blood purification device

INTERVENTION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non emergent cardiac surgery requiring cardiopulmonary bypass with expected CPB time over 90 minutes (double valve replacement or valve replacement plus CABG).
• Written informed consent from patient or legal surrogates.

You may not qualify if:

• Transplant receptor.
• Advanced Chronic Kidney Disease (CKD 4 or 5).
• Renal replacement therapy in the last 90 days.
• Documented intolerance to study device.
• Pregnancy.
• Immunosuppressive treatment or steroids (prednisone \> 0.5 mg/kg/day or equivalent).
• Autoimmune disorder.
• Coexisting illness with a high probability of death (inferior to 6 months).

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead
• University of Barcelona: collaborator
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: collaborator
• Germans Trias i Pujol Hospital: collaborator

Study Sites (1)

Universitat de Barcelona

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Related Publications (1)

• Perez-Fernandez X, Ulsamer A, Camara-Rosell M, Sbraga F, Boza-Hernandez E, Moret-Ruiz E, Plata-Menchaca E, Santiago-Bautista D, Boronat-Garcia P, Gumucio-Sanguino V, Penafiel-Munoz J, Camacho-Perez M, Betbese-Roig A, Forni L, Campos-Gomez A, Sabater-Riera J; SIRAKI02 Study Group. Extracorporeal Blood Purification and Acute Kidney Injury in Cardiac Surgery: The SIRAKI02 Randomized Clinical Trial. JAMA. 2024 Nov 5;332(17):1446-1454. doi: 10.1001/jama.2024.20630.

  PMID: 39382234 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury; Renal Insufficiency, Chronic; Insulin Resistance

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 17, 2025
• Study Start: October 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)