Intravenous Fish Oil Based Lipid Emulsion to Enhance Recovery in High-Risk Cardiac Surgery Patients (MODIFY CSX)

Intravenous Fish Oil Based Lipid Emulsion to Enhance Recovery in High-Risk Cardiac Surgery Patients: a Phase II Multicenter Trial - A Randomized, Placebo-controlled Trial -

The MODIFY CSX study is a prospective, randomized, placebo-controlled trial conducted in heart centers in Germany and Italy.

A total of 550 high-risk cardiac surgery patients will receive either 0.20 g fish oil/kg body weight (BW) + standard of care versus same volume of placebo (NaCl) + standard of care.

Study Overview

• Status: Recruiting
• Conditions: Cardiopulmonary Bypass; Intensive Care Unit; Elective Cardiac Surgery; High Risk Patients; Coronary Artery Bypass Grafting (CABG); Valvular Heart Surgery; Multiple Valve Surgeries; Combined Cardiac Procedures; Aortic Surgical Procedures; Adult Patients ≥ 18 Years; Combined Valve and CABG; Combined Cardiac and Aortic Surgical Procedures
• Intervention / Treatment: Drug: Fish Oil; Drug: Intravenous 0.9% Sodium Chloride

Detailed Description

The proposed hypothesis is that the therapeutic strategy tested in this randomized trial will decrease the occurrence of postoperative atrial fibrillation, which ultimately leads to faster time to discharge alive. This in turn significantly improves the patients' mid and long-term outcomes and dramatically reduces associated healthcare related costs.

Duration of intervention: until discharge from ICU, death or postoperative day 7 on ICU, whichever comes first.

Treatment Group: Patients will receive 0.20 g fish oil/kg BW/d (≙ 2 mL Omegaven®/kg BW/d).

Control Group: Patients will receive 0,9% NaCl in dose 2 mL/kg BW/d (placebo).

Follow-up per patient: at day 30, months 3, 6, and 12.

Primary endpoint (Phase II study):

The primary endpoint for this phase II clinical trial is the onset and occurence of atrial fibrillation after cardiac surgery (AFACS), incorporating atrial fibrillation, atrial flutter, and atrial tachycardia, until day 7 after surgery (on ICU and normal ward).

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christian Stoppe, Prof. Dr.; Phone Number: 49-931-20130001; Email: cstoppe@gcp-service.com
• Study Contact Backup: Name: Ellen Dresen, Dr.; Phone Number: +49 931-201 30392; Email: Dresen_E@ukw.de

Study Locations

• Germany
  • Augsburg, Germany
    • Not yet recruiting
    • University Hospital Augsburg
    • Contact: Philipp Simon, Prof. Dr.; Phone Number: +49 821 400 - 2371; Email: philipp.simon3@uk-augsburg.de
    • Contact: Manfred Weiss, Prof. Dr.; Email: Manfred.Weiss@uk-augsburg.de
    • Principal Investigator: Philipp Simon, Prof. Dr.
  • Berlin, Germany
    • Recruiting
    • Charité Universitätsmedizin Berlin
    • Contact: Maren Kleine-Brüggeney, M.D; Email: maren.kleine-brueggeney@dhzc-charite.de
    • Contact: Sascha Ott, M.D; Phone Number: 49-30-4593-2600; Email: sascha.ott@dhzc-charite.de
    • Principal Investigator: Sascha Ott, M.D.
  • Bonn, Germany
    • Recruiting
    • University of Bonn
    • Contact: Florian Piekarski, M.D; Email: Florian.Piekarski@ukbonn.de
    • Principal Investigator: Maria Wittmann, M.D.
    • Contact: Maria Wittmann, M.D; Phone Number: 49-228 287-15074-14137; Email: maria.wittmann@ukbonn.de
  • Göttingen, Germany
    • Recruiting
    • University Hospital Goettingen
    • Contact: Reiner Wäschle, M.D; Phone Number: 49-551-3967701; Email: Reiner.Waeschle@med.uni-goettingen.de
    • Contact: Anselm Bräuer, M.D.; Email: anselm.braeuer@med.uni-goettingen.de
    • Principal Investigator: Reiner Waeschle, M.D.
  • Hamburg, Germany
    • Recruiting
    • University Hospital Hamburg-Eppendorf
    • Contact: Bernd Saugel, Prof. Dr.; Phone Number: +49 40 7410-52415; Email: b.saugel@uke.de
    • Contact: Ekaterina Nekhaeva, Dr.; Email: e.nekhaeva@uke.de
    • Principal Investigator: Bernd Saugel, Prof. Dr.
  • Kiel, Germany
    • Recruiting
    • University Medical Center Schleswig-Holstein
    • Contact: Matthias Lindner, M.D; Email: Matthias.Lindner@uksh.de
    • Contact: Radke David, M.D; Phone Number: 49-431 - 500 20801; Email: David.Radke@uksh.de
    • Principal Investigator: David Radke, M.D.
  • Mainz, Germany
    • Recruiting
    • University Hospital Mainz
    • Contact: Daniel Dürr, Prof. Dr.; Phone Number: +49 6131 17-2106; Email: Daniel.Duerr@unimedizin-mainz.de
    • Contact: Jan Beer, Dr.; Email: Jan.Beer@unimedizin-mainz.de
    • Principal Investigator: Daniel Dürr
  • Münster, Germany
    • Recruiting
    • University hospital Muenster
    • Contact: Alexander Zarbock, M.D; Phone Number: 49-251-83-44017; Email: zarbock@uni-muenster.de
    • Contact: Melanie Meersch-Dini, M.D; Email: meersch@ukmuenster.de
    • Principal Investigator: Alexander Zarbock, M.D.
  • Rostock, Germany
    • Not yet recruiting
    • University Medical Center Rostock
    • Contact: Jens-Christian Schewe, M.D.; Phone Number: 49-431-500 20801; Email: Jens-Christian.Schewe@med.uni-rostock.de
    • Contact: Benjamin Löser, M.D.; Phone Number: 49-381-494 146234; Email: Benjamin.loeser@med.uni-rostock.de
    • Principal Investigator: Jens-Christian Schewe, M.D.
  • Stuttgart, Germany
    • Not yet recruiting
    • Robert Bosch Medical Center
    • Contact: Christian Wunder, M.D.; Phone Number: 49-711-8101 3484; Email: christian.wunder@rbk.de
    • Contact: Magdalena Rufa, M.D.; Phone Number: 49-711-8101 5069; Email: magdalena.rufa@rbk.de
    • Principal Investigator: Christian Wunder, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent prior to study participation
2. Adult patients (≥ 18 years)
3. Patients scheduled to undergo elective cardiac surgery with the use of CPB, who are defined as high risk based on having (i) one of the following surgical procedures: valvular heart surgery only, CABG, combined valve and CABG, multiple valve surgeries, combined cardiac procedures, aortic surgical procedures (aortic arch and/or descending aorta; aortic valve+ascending aorta) and (ii) at least one of the following additional risk factors: (a) a high perioperative risk profile, defined as predicted operative mortality of ≥8% (EuroSCORE II), (b) age ≥70, (c) Clinical Frailty Score 4 or more, (d) urgent surgery (defined as to be performed within 24-48 hours after admission), (e) left ventricular ejection fraction <35%

Exclusion Criteria:

1. Known hypersensitivity to fish oil/fish products or egg protein
2. Pregnancy or lactation period
3. Previous history of chronic atrial fibrillation, atrial flutter and/or atrial tachyarrhythmia
4. Inability or unwillingness of individual to give written informed consent
5. Not expected to survive an additional 48 hours from screening evaluation
6. Lack of commitment to full, aggressive care (anticipated withholding or withdrawing treatments in the first week but isolated "Do not Resuscitate" [DNR] acceptable)
7. Patients admitted with diabetic ketoacidosis or non-ketotic hyperosmolar coma
8. Patients receiving extracorporeal mechanical assist device (e.g. ECLS, or IABP) or advanced heart failure therapies (e.g. TAH, VAD)
9. Enrolment in anyinterventional trial within the last 30 days
10. Already receiving FO-containing medical nutrition products
11. Severe malnutrition (as defined by the BMI <18.5)
12. Severe liver dysfunction defined by Child Pugh Class C.
13. Severe chronic kidney dysfunction defined by the National Kidney Foundation (NKF) stage 4 and 5 by using the glomerular filtration rate (GFR <30ml/min)
14. Known severe coagulation disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Patients will receive 0.20 g fish oil/kg BW/d (≙2 mL Omegaven®/kg BW/d).	Drug: Fish Oil; Omegaven® is a 10% fish oil emulsion with a high percentage of long-chain n-3 fatty acids - mainly eicosapentaenoic acid and docosahexaenoic acid. It optimises the fatty acid pattern in parenteral nutrition and is a source of polyunsaturated n-3 fatty acids as cell membrane components and precursors for eicosanoids. Omegaven® is manufactured by Fresenius-Kabi, Germany and is available in 100 mL bottles for study purpose. Each 100 mL of Omegaven® contains 10 g of fish oil (0.1 g/mL). Timeframe: Day -1: 0.20 g fish oil/kg BW/d (the treatment should be started 24 to 3 h before surgery, can be given as 3-6 hours infusion); intraoperative day 0: no dose; postoperative day 0: 0.20 g fish oil/kg BW/d; postoperative days 1 to max. 7): 0.20 g fish oil/kg BW/d; Other Names: Omegaven®
Placebo Comparator: Control group; Patients will receive 0,9% NaCl in volume 2 mL/kg BW/d (placebo).	Drug: Intravenous 0.9% Sodium Chloride; Intravenous 0.9% Sodium Chloride (volume 2 mL/kg BW/d) provided at the same timepoints as the intervention.; Other Names: Saline Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial fibrillation	The primary objective is to demonstrate superiority of fish oil compared to placebo in the prevention of atrial fibrillation until 7 days after surgery. This clinical endpoint is assessed as part of the clinical practice.	Postoperative days 0-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay	Number of days alive in the ICU	ICU discharge (approximately 3-4 days after surgery)
Hospital length of stay	Number of days alive in the hospital	Hospital discharge (approximately 1-2 weeks after surgery)
Mechanical ventilation	Duration of mechanical ventilation	Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up
Adverse Events	AEs leading to discontinuation/AEs at least possibly related to the IMP/SAEs	Preoperative day -1 to 12 months follow-up
Delta Sequential Organ Failure Assessment Score (SOFA) Score	A scoring system that assesses the performance of several organ systems in the body (neurologic, blood, liver, kidney, and blood pressure/hemodynamics) and assigns a score based on the data obtained in each category.	Postoperative days 0-7
Stroke	Incidence of stroke	Postoperative days 0-7
Inotropics/vasopressors	Duration of inotropic/vasopressor support	Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up
Acute Kidney Injury	Kidney Disease: Improving Global Outcomes [KDIGO] stages 1-3	Postoperative days 0-7
Infection rate	Number of infections	Postoperative days 0-7
Survival status	Overall survival	ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up, months 3, 6, and 12 follow-up
Quality of Life (SF-36)	To measure the quality of life	Screening (preoperative day -7 until day -1), day 30 follow-up, 3, 6, and 12 months follow-up
Postoperative bleeding	Bleeding after surgery	Postoperative days 0-7
Physical activity assessment	Katz activities of daily living (ADL) and Lawton's Instrumental ADL (IADL)	Screening (preoperative day -7 until day -1), day 30 follow-up, 3 and 6 months follow-up
Days alive and out of hospital	Time to be alive and discharge from hospital	Day 30 follow-up, 3, 6, and 12 months follow-up
Time to discharge alive	Time to be alive and discharged from ICU/hospital	ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
Weaning from cardiopulmonary bypass (CPB)	Number of attempts to wean from CPB during surgery	Intraoperative day 0 (during surgery)
Persistent Organ Dysfunction + Death	Requiring supportive technologies during the convalescent phase of critical illness	Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up
ICU Readmission rates	Readmission to ICU	Day 30 follow-up, 3, 6, and 12 months follow-up
Hospital Readmission rates	Readmission to hospital	Day 30 follow-up, 3, 6, and 12 months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optional tertiary endpoint: Ultrasound measurement of thigh skeletal muscle mass	Ultrasound measurement of thigh skeletal muscle mass	Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
Optional tertiary endpoint: Functional Status Score for Intensive Care Unit (FSS-ICU)	Functional Status Score for Intensive Care Unit (FSS-ICU)	Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
Optional tertiary endpoint: Short Physical Performance Battery test (SPPB)	Short Physical Performance Battery test (SPPB)	Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
Optional tertiary endpoint: Hand grip/held dynamometer	Hand grip/held dynamometer	Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
Optional tertiary endpoint: Inflammatory response	Inflammatory response and immune function as measured by markers of the clinical routine (e.g. IL6, IL10, CRP, white blood cell count [WBC], PCT, TNF-a)	Intraoperative day 0, postoperative days 0-7
Optional tertiary endpoint: Left ventricular ejection fraction	Left ventricular ejection fractLeft ventricular ejection fractionion	Preoperative day -1, hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up, 3 and 6 months follow-up
Optional tertiary endpoint: Manual Muscle Testing (MMT)	Manual Muscle Testing (MMT)	Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
Optional tertiary endpoint: Vasoactive-Inotropic Score (VIS)	Vasoactive-Inotropic Score (VIS)	Postoperative days 0-7
Optional tertiary endpoint: Therapeutic Intervention Scoring System (TISS)	A method for measuring workload and calculating costs in the ICU	Postoperative days 0-7
Optional tertiary endpoint: Development of delirium	Assessed by the CAM ICU score	Postoperative days 0-7
Optional tertiary endpoint: Hemodynamic parameters	Adequate hemodynamic support, as defined by stable Cardiac Index, cardiac output (CO), Cardiac Power Index, mean arterial pressure (MAP), central vein pressure (CVP), pulmonary artery diastolic pressure (to be measured every 8 hours for first 72 hours post-op or until removal of pulmonary artery catheter, whatever comes first	Intraoperative day 0, postoperative days 0-7
Optional tertiary endpoint: Clinical frailty scale	A 9-point scale that quantifies frailty based on function in individual patients	Screening (preoperative day -1 until day -7), day 30 follow-up, 3 months follow-up
Optional tertiary endpoint: Simplified Acute Physiology Score (SAPS)	Estimates the probability of mortality for ICU patients on admission	Postoperative days 0-7
Optional tertiary endpoints: Further routine biomarkers	Further routine biomarkers: creatinine, urea, bilirubin, troponin, triglycerides if available	Intraoperative day 0, postoperative days 0-7
Separate Sub-study	Serial blood samples and - if available - tissue samples from patients (if these result from the routine surgical procedure) will be collected in concerning patients at the day before (only blood samples), during surgery (only tissue sample if available), and once daily after surgery while the patients are on ICU (only blood samples): Specialized pro-resolving mediators (SPMs) and more specific markers of the inflammatory response, such as the production of leukotriene B5 (LTB5), leukotriene B4 (LTB4), 5-hydroxyeicosapentaenoic acid (5-HEPE) and production of 5-hydroxyeicosatetraenoic acid (5-HETE); SPMs, such as maserins and resolvins; Oxidative stress (oxidative reduction potential, Malondialdehyde); Membrane incorporation of PUFAs (white blood cells) & tissue samples; Activation of survival kinases (such as extracellular-signal regulated	Preoperative day -1, intraoperative day 0, postoperative days 0-7, hospital discharge (approximately 1-2 weeks after surgery)

Collaborators and Investigators

• Sponsor: GCP-Service International West GmbH
• Collaborators: Charite University, Berlin, Germany; University Hospital Muenster; University Hospital, Bonn; University Hospital Schleswig-Holstein; Johannes Gutenberg University Mainz; Universitätsklinikum Hamburg-Eppendorf; Wuerzburg University Hospital; Robert Bosch Medical Center; University Hospital Goettingen; University Medical Center Rostock; University Hospital Augsburg
• Investigators: Study Director: Christian Stoppe, Prof. Dr., Wuerzburg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: intensive care unit; atrial fibrillation; atrial flutter; fish oil; atrial tachycardia; elective cardiac surgery; medical nutrition therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Atrial Flutter; Lipids; Inorganic Chemicals; Chlorine Compounds; Oils; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride; fish oil triglycerides; Fish Oils
• Other Study ID Numbers: MODIFY CSX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No