E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Given the recently meta-analyzed data from previous RCTs about fish oil , we hypothesize that the provision of intravenous (i.v.) FO (0.20 g/kg and 0.50 g/kg) to cardiac surgery patients may reduce the development of postoperative infections and organ dysfunctions through modulation of cytokines and chemokine release that regulate the activity of various immune cell populations. |
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E.1.1.1 | Medical condition in easily understood language |
patients undergoing cardiac surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine safety and efficacy of i.v. fish oil doses of 0.20 g/kg/d and 0.50 g/kg/d compared to a control group in high risk patient undergoing cardiac surgery. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of fish oil application on the peri-operative systemic inflammatory response and immune status. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Age ≥ 18 years scheduled to undergo elective cardiac surgery with the use of CPB and cardioplegic Arrest: Included patients should exhibit a significantly increased perioperative risk profile defined as a predictive operative mortality EuroSCORE 5% or by complex/combined surgical procedures. 2) Written informed consent prior to study participation
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E.4 | Principal exclusion criteria |
1) Known hypersensitivity to fish oil/ fish products or egg protein 2) Emergency open heart surgery 3) Severe dyslipidemia (triglycerides > 400 mg/dl) 4) Pregnancy or lactation period 5) Inability or unwillingness of individual to give written informed consent 6) Simultaneous participation in another clinical trial 7) Not study related fish oil supplementation 8) Severe renal or hepatic insufficiency (Patients with Cirrhosis Child’s Class C Liver Disease) 9) Not expected to survive an additional 48 hours from screening evaluation 10) Lack of commitment to full, aggressive care (anticipated withholding or withdrawing treatments in the first week but isolated DNR acceptable) 11) Patients admitted with Diabetic Ketoacidosis or non-ketotic hyperosmolar coma 12) Patients receiving and extracorporeal mechanical assist device (e.g. ECLS, or IABP) or for advanced heart failure therapies (e.g. TAH, VAD)
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E.5 End points |
E.5.1 | Primary end point(s) |
- safety and efficacy - feasibility
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Depending on end point (daily evaluation) |
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E.5.2 | Secondary end point(s) |
Anti-inflammatory response Oxidative stress Inflammatory response on the immune system Effect on body’s immune competence Immune phenotype and activation of immune cells Safety parameters in blood Pharmacokinetic profile Change in SOFA score ICU length of stay Hospital length of stay Length of ventilation Number of infection Persistent Organ Dysfunction+death (POD+death) 30-day mortality Hospital mortality rate Quality of Life after 3 and 6 month Membrane incorporation of PUFAs in immune cells activation of protective survival kinases such as ERK1/2 and Akt adverse and serious adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during the ICU stay, at follow up visit day 30 (30-day mortality), month 3 (SF36) and month 6 (SF36) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Reason, time point, and specific reason for premature study termination of each subject will be documented. The investigator should determine a primary reason for premature study termination of each subject. All relevant safety data until subject’s study termination will be collected and reported. The study will entirely be terminated in case the risk-benefit-ratio changes in such way, that premature study termination is indicated in order to protect subject’s health.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |