Intravenous Fish Oil Based Lipid Emulsion to Enhance Recovery in High-Risk Cardiac Surgery Patients.

Cardiac Surgery Clinical Trial

— MODIFYCSX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06279793
• Other study ID #: MODIFYCSX
• Status: Recruiting
• Phase: Phase 2
• Start date: February 15, 2024
• Est. completion date: December 1, 2025

Study information

• Verified date: September 2023
• Source: GCP-Service International West GmbH
• Contact: Christian Stoppe, Prof. Dr.
• Phone: +49 931 201-30001
• Email: cstoppe[@]gcp-service.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposing study is a randomized, double-blind, controlled trial of about 120 patients in 10 centers in Germany. This trial will be started in Germany and recruited mainly at powerful German heart centers only.

In this prospective randomized controlled blinded multicenter trial, a total of 120 high-risk cardiac surgery patients will receive either standard of care + OMEGAVEN at 0.20 g/kg ideal body weight (IBW) versus placebo + standard of care.

Description:

The proposed hypothesize is that the therapeutic strategy tested in this randomized trial will decrease the occurrence of postoperative atrial fibrillation, which ultimately lead to faster time to discharge alive. This 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 Omegaven® in dose 0.20 g/kg/d.

Control Group: Patients will receive 0,9% NaCl in dose 0.20 g/kg/d (placebo).

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

Primary endpoint (phase II study):

The primary endpoint for this phase II clinical trial will be the presence of new onset atrial fibrillation after cardiac surgery (AFACS) until day 7 after surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 cardiopulmonary bypass (CPB), who are defined as high risk based on having (i) combined valve/coronary artery bypass graft (CABG) or multiple valve surgeries, or combined cardiac/aortic surgical procedures and (ii) one of the following additional risk factors:

1. a high perioperative risk profile, defined as predicted operative mortality of = 8% (European System for Cardiac Operative Risk Evaluation, EuroSCORE II).

2. Age >70

3. Clinical Frailty Score 4 or more

4. Urgent surgery (defined as to be performed within 24-48 hours after admission)

5. Left ventricular ejection fraction <35%

Exclusion Criteria:

1. Known hypersensitivity to fish oil (FO)/ fish products or egg protein

2. Pregnancy or lactation period

3. Previous history of 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 and extracorporeal mechanical assist device (e.g. extracorporal life support systems [ECLS], or intra-aortic ballon pump [IABP]) or for advanced heart failure therapies (e.g. platelet aggregation inhibitors [TAH], ventricular assist devices [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)1

14. Known severe coagulation disorder

Related Conditions & MeSH terms

• Cardiac Surgery
• Cardiopulmonary Bypass
• High Risk Patients
• Intensive Care Unit

Intervention

Drug:
• Long-chain n-3 fatty acids
Omegaven is a 10% fish oil emulsion supplement with a high percentage of long-chain n-3 fatty acids - mainly eicosapentaenoic acid and docosahexaenoic acid. It is a lipid emulsion supplement that 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 grams of fish oil (10 ml/gm or 0.1grams/ml). Timeframe: Day -1: The treatment should be started 24 to 3 h before surgery, can be given as 3-6 hours infusion. Intraoperative Day: No dose Post OP (Day 0): study drug 0.20 grams/kg IBW/day Post OP ( Day 1 to max Day 7): study drug 0.20 grams/kg IBW/day
• Intravenous 0.9% Sodium Chloride
Intravenous 0.9% Sodium Chloride

Locations

Country	Name	City	State
Germany	RWTH Aachen University	Aachen
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	University of Bonn	Bonn
Germany	Universität Göttingen	Göttingen
Germany	University Medical Center Schleswig-Holstein	Kiel
Germany	University of Muenster	Münster

Sponsors (3)

Lead Sponsor	Collaborator
GCP-Service International West GmbH	Charite University, Berlin, Germany, Wuerzburg University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Optional-Ultrasound measurement	nested sub-study of skeletal muscle mass	screening, ICU discharge, hospital discharge
Other	Optional-Functional Status Score for Intensive Care Unit	Functional Status Score	screening, ICU discharge
Other	Optional-Short Physical Performance Battery test	nested sub-study	screening, ICU discharge, hospital discharge
Other	Optional-Hand grip dynamometer	nested sub-study	screening, ICU discharge, hospital discharge
Other	Optional-Hand held dynamometer	nested sub-study	screening, ICU discharge, hospital discharge
Other	Optional-Manual Muscle Testing	nested sub-study	screening, ICU discharge, hospital discharge
Other	Optional-Left ventricular ejection function	if available	hospital discharg, 30 days, 3, 6 and 12 months
Other	Optional-Markers of inflammation	e.g. procalcitonin [PCT] interleukine-6 [IL-6], white blood cells [WBC]	day 0-7
Other	Optional-Hemodynamics	Adequate hemodynamic support, as defined by stable Cardiac Index (CI), cardiac output (CO), Cardiac Power Index, mean arterial pressure (MAP), central vein pressure (CVP), pulmonary artery diastolic pressure	day 0-7
Other	Sub-study	a serial blood samples and tissue samples( if available from the routine surgical procedure only).	day -1, day 0-7, hopital discharge
Primary	Atrial fibrillation	The primary objective is to demonstrate superiority of Omegaven® compared to placebo in the prevention of atrial fibrilation	Until 7 days after surgery
Secondary	Weaning from cardiopulmonary bypass (CPB)	Number of attempts to wean from CPB during surgery	During surgery
Secondary	Time to discharge alive	time to be alive and discharge from Intensive Care Unit (ICU)	at ICU discharge
Secondary	Persistent Organ Dysfunction + Death	requiring supportive technologies during the convalescent phase of critical illness	day 30
Secondary	Days alive and out of hospital	time to be alive and discharge from Hospital	30 days, 3, 6 and 12 months
Secondary	Hospital length of stay	Number of days alive in the ICU/Hosp	at hospital discharge
Secondary	ICU length of stay	Number of days alive in the ICU/Hosp	at ICU discharge
Secondary	Simplified Acute Physiology Score	Estimates the probability of mortality for ICU patients on admission	day 0-7
Secondary	Therapeutic Intervention Scoring System	a method for measuring workload and calculating costs in the ICU	day 0-7
Secondary	ICU and Hospital Readmission rates	readmission to ICU and hospital	30 days, 3, 6 and 12 months
Secondary	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.	day 0-7
Secondary	Mechanical ventilation	Duration of mechanical ventilation	day -1-7
Secondary	Stroke	Incidence of stroke	day 0-7
Secondary	Acute Kidney Injury	Kidney Disease: Improving Global Outcomes [KDIGO] stages 1-3	day 0-7
Secondary	Infections rate	Number of infections	screening, day -1-7
Secondary	Clinical frailty scale	a 9-point scale that quantifies frailty based on function in individual patients	screening, day 30, 3 months
Secondary	Development of delirium	assessed by the CAM ICU score	day 0-7, ICU discharge
Secondary	Survival status	overall survival	hospital discharge, 30 days, 3, 6 and 12 months
Secondary	Physical activity assessment	Katz activities of daily living (ADL) and Lawton's Instrumental ADL (IADL)	screening, 30 days, 3, and 6 months
Secondary	Quality of Life (SF-36)	to measure thew quality of life	screening, 30 days, 3, 6, and 12 months
Secondary	Adverse Events	possibly related to the investigational product	from day 0 to 12 months
Secondary	Postoperative bleeding	bleeding after surgery	day 0-7