Adult Patients ≥ 18 Years, Aortic Surgical Procedures, Cardiopulmonary Bypass, Combined Cardiac and Aortic Surgical Procedures, Combined Cardiac Procedures, Combined Valve and CABG, Coronary Artery Bypass Grafting (CABG), Elective Cardiac Surgery, High Risk Patients, Intensive Care Unit, Multiple Valve Surgeries, Valvular Heart Surgery
Conditions
Keywords
intensive care unit, elective cardiac surgery, fish oil, medical nutrition therapy, atrial fibrillation, atrial flutter, atrial tachycardia
Brief summary
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.
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).
Interventions
DRUGFish 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
DRUGIntravenous 0.9% Sodium Chloride
Intravenous 0.9% Sodium Chloride (volume 2 mL/kg BW/d) provided at the same timepoints as the intervention.
Sponsors
GCP-Service International West GmbH
University Hospital, Bonn
University Hospital Muenster
University Hospital Goettingen
Charite University, Berlin, Germany
Wuerzburg University Hospital
Johannes Gutenberg University Mainz
University Hospital Augsburg
Universitätsklinikum Hamburg-Eppendorf
University Medical Center Rostock
University Hospital Schleswig-Holstein
Robert Bosch-Krankenhaus Stuttgart
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Patients as well as clinical staff and outcome assessors not involved in the study will be blinded to study intervention allocation.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 any other interventional trial will be discussed with the coordinating investigator on a case-by-case scenario and requires sponsor approval before inclusion 10. Already receiving special FO-enriched 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Atrial fibrillation | Postoperative days 0-7 | The primary objective is to demonstrate superiority of fish oil compared to placebo in the prevention of atrial fibrillation after cardiac surgery (AFACS), incorporating atrial fibrillation, atrial flutter and atrial tachycardia, until 7 days after surgery. This clinical endpoint is assessed as part of the clinical practice. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Duration of mechanical ventilation |
| Adverse Events | Preoperative day -1 to 12 months follow-up | AEs leading to discontinuation/AEs at least possibly related to the IMP/SAEs |
| Delta Sequential Organ Failure Assessment Score (SOFA) Score | Postoperative days 0-7 | 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. |
| Stroke | Postoperative days 0-7 | Incidence of stroke |
| Inotropics/vasopressors | Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up | Duration of inotropic/vasopressor support |
| Acute Kidney Injury | Postoperative days 0-7 | Kidney Disease: Improving Global Outcomes \[KDIGO\] stages 1-3 |
| Infection rate | Postoperative days 0-7 | Number of infections |
| Survival status | 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 | Overall survival |
| Quality of Life (SF-36) | Screening (preoperative day -7 until day -1), day 30 follow-up, 3, 6, and 12 months follow-up | To measure the quality of life |
| Postoperative bleeding | Postoperative days 0-7 | Bleeding after surgery |
| Time to ICU discharge alive | ICU discharge (approximately 3-4 days after surgery) | Number of days alive in the ICU |
| Time to hospital discharge alive | Hospital discharge (approximately 1-2 weeks after surgery) | Number of days alive in the hospital |
| Physical activity assessment | Screening (preoperative day -7 until day -1), day 30 follow-up, 3 and 6 months follow-up | Katz activities of daily living (ADL) and Lawton Instrumental ADL (IADL) |
| Days alive and out of hospital | Day 30 follow-up, 3, 6, and 12 months follow-up | Time to be alive and discharge from hospital |
| Time to discharge alive | ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery) | Time to be alive and discharged from ICU/hospital |
| Weaning from cardiopulmonary bypass (CPB) | Intraoperative day 0 (during surgery) | Number of attempts to wean from CPB during surgery |
| Persistent Organ Dysfunction + Death | Postoperative days 0-7, ICU discharge (approximately 3-4 days after surgery), hospital discharge (approximately 1-2 weeks after surgery), day 30 follow-up | Requiring supportive technologies during the convalescent phase of critical illness |
| ICU Readmission rates | Day 30 follow-up, 3, 6, and 12 months follow-up | Readmission to ICU |
| Hospital Readmission rates | Day 30 follow-up, 3, 6, and 12 months follow-up | Readmission to hospital |
Countries
Germany
Contacts
CONTACTChristian Stoppe, Prof. Dr.
CONTACTEllen Dresen, Dr.
STUDY_DIRECTORChristian Stoppe, Prof. Dr.
Wuerzburg University Hospital
Outcome results
None listed