Clinical trial NCT06279793: Intravenous Fish Oil Based Lipid Emulsion to Enhance Recovery in High-Risk Cardiac Surgery Patients
Official title: 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 -
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Intensive Care Unit
Coronary Artery Bypass Grafting (CABG)
High Risk Patients
Cardiopulmonary Bypass
Elective Cardiac Surgery
Valvular Heart Surgery
Multiple Valve Surgeries
Combined Cardiac Procedures
Aortic Surgical Procedures
Keywords: intensive care unit
elective cardiac surgery
fish oil
medical nutrition therapy
atrial fibrillation
Lead sponsor: GCP-Service International West GmbH
Sponsor class: INDUSTRY
Collaborators: name: University Hospital, Bonn
name: University Hospital Muenster
name: University Hospital Goettingen
name: University Hospital Schleswig-Holstein
name: Charite University, Berlin, Germany
name: Wuerzburg University Hospital
name: Johannes Gutenberg University Mainz
name: University Hospital Augsburg
name: Universitätsklinikum Hamburg-Eppendorf
First posted: 2024-02-28
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will be stratified by site, employing a web-based system using a 1:1 ratio to either intravenous fish oil-based lipid emulsion (Omegaven®), or placebo.
Primary purpose: PREVENTION

Brief summary: The MODIFY CSX study is a prospective, randomized, placebo-controlled trial conducted in heart centers in Germany.

A total of 120 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.

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 be the onset and occurence of atrial fibrillation after cardiac surgery (AFACS) until day 7 after surgery (on ICU and normal ward).

Eligibility criteria: 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

Primary outcomes:
measure: Atrial fibrillation
timeFrame: Postoperative days 0-7
Secondary outcomes:
measure: Mechanical ventilation
timeFrame: Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up
measure: Adverse Events
timeFrame: Preoperative day -1 to 12 months follow-up
measure: Delta Sequential Organ Failure Assessment Score (SOFA) Score
timeFrame: Postoperative days 0-7
measure: Stroke
timeFrame: Postoperative days 0-7
measure: Inotropics/vasopressors
timeFrame: Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up
measure: Acute Kidney Injury
timeFrame: Postoperative days 0-7
measure: Infection rate
timeFrame: Postoperative days 0-7
measure: Survival status
timeFrame: 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
measure: Quality of Life (SF-36)
timeFrame: Screening (preoperative day -7 until day -1), day 30 follow-up, 3, 6, and 12 months follow-up
measure: Postoperative bleeding
timeFrame: Postoperative days 0-7
measure: ICU length of stay
timeFrame: ICU discharge (approximately 3-4 days after surgery)
measure: Hospital length of stay
timeFrame: Hospital discharge (approximately 1-2 weeks after surgery)
measure: Physical activity assessment
timeFrame: Screening (preoperative day -7 until day -1), day 30 follow-up, 3 and 6 months follow-up
measure: Days alive and out of hospital
timeFrame: Day 30 follow-up, 3, 6, and 12 months follow-up
measure: Time to discharge alive
timeFrame: ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
measure: Weaning from cardiopulmonary bypass (CPB)
timeFrame: Intraoperative day 0 (during surgery)
measure: Persistent Organ Dysfunction + Death
timeFrame: Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up
measure: ICU Readmission rates
timeFrame: Day 30 follow-up, 3, 6, and 12 months follow-up
measure: Hospital Readmission rates
timeFrame: Day 30 follow-up, 3, 6, and 12 months follow-up
Other outcomes:
measure: Optional tertiary endpoint: Ultrasound measurement of thigh skeletal muscle mass
timeFrame: Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
measure: Optional tertiary endpoint: Functional Status Score for Intensive Care Unit (FSS-ICU)
timeFrame: Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
measure: Optional tertiary endpoint: Short Physical Performance Battery test (SPPB)
timeFrame: Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
measure: Optional tertiary endpoint: Hand grip/held dynamometer
timeFrame: Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
measure: Optional tertiary endpoint: Inflammatory response
timeFrame: Intraoperative day 0, postoperative days 0-7
measure: Optional tertiary endpoint: Left ventricular ejection fraction
timeFrame: Preoperative day -1, hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up, 3 and 6 months follow-up
measure: Optional tertiary endpoint: Manual Muscle Testing (MMT)
timeFrame: Screening (preoperative day -7 until day -1), ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery)
measure: Optional tertiary endpoint: Vasoactive-Inotropic Score (VIS)
timeFrame: Postoperative days 0-7
measure: Optional tertiary endpoint: Therapeutic Intervention Scoring System (TISS)
timeFrame: Postoperative days 0-7
measure: Optional tertiary endpoint: Development of delirium
timeFrame: Postoperative days 0-7
measure: Optional tertiary endpoint: Hemodynamic parameters
timeFrame: Intraoperative day 0, postoperative days 0-7
measure: Optional tertiary endpoint: Clinical frailty scale
timeFrame: Screening (preoperative day -1 until day -7), day 30 follow-up, 3 months follow-up
measure: Optional tertiary endpoint: Simplified Acute Physiology Score (SAPS)
timeFrame: Postoperative days 0-7
measure: Optional tertiary endpoints: Further routine biomarkers
timeFrame: Intraoperative day 0, postoperative days 0-7
measure: Separate Sub-study
timeFrame: Preoperative day -1, intraoperative day 0, postoperative days 0-7, hospital discharge (approximately 1-2 weeks after surgery)
Locations:
city: Augsburg
country: Germany
facility: University Hospital Augsburg
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: University of Bonn
city: Göttingen
country: Germany
facility: University Hospital Goettingen
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Kiel
country: Germany
facility: University Medical Center Schleswig-Holstein
city: Mainz
country: Germany
facility: University Hospital Mainz
city: Muenster
country: Germany
facility: University Hospital Muenster
Study officials:
affiliation: Wuerzburg University Hospital
name: Christian Stoppe, Prof. Dr.
role: STUDY_DIRECTOR
References: