Fish OIL Optimal dosE Determination Study

Study Overview
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Brief Summary
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The primary objective of this trial is to determine the safety and efficacy of IV fish oil doses of 0.20 g/kg and 0.50 g/kg, compared to a control group, in critically ill patients with severe sepsis by examining organ function, blood safety and biochemical parameters, markers of systemic inflammation and innate immunological parameters

Detailed Description
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Objectives: The overall objective is to determine the effect of IV fish oil on 28-day mortality of critically ill patients with severe sepsis. However, prior to such a large trial, we need to determine the optimal dose of IV fish oils in this population. Therefore, the primary objective of this proposal (FOILED) is to determine the safety and efficacy of IV fish oil doses of 0.20 g/kg and 0.50 g/kg, compared to a control group, in critically ill patients with severe sepsis by examining organ function, blood safety and biochemical parameters, markers of systemic inflammation and innate immunological parameters. Study Design: This is a multi-centre, open-label, phase I dose ranging clinical trial with prospective controls. Setting: 2 tertiary care ICUs in Germany (Universitätsklinikum Carl Gustav Carus, Dresden and University Hospital Giessen and Marburg, Giessen). Patients: Mechanically ventilated adult patients (>18 years old) admitted to ICU with clinical evidence of sepsis, sepsis associated organ dysfunction, and high expression of inflammatory cytokines.

Official Title
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Multi-centre, Open-label, Phase II Clinical Trial for Determination of the Optimal Dose of Fish Oil in Patients With Severe Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Dietary Supplement: 0.20 gm/kg fish oil
* Dietary Supplement: 0.50 gm/kg fish oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ICU patients Requiring invasive or non-invasive ventilation Clinical evidence of sepsis Presence of one or more organ failures Exclusion Criteria: >24 hours from admission to ICU to time of consent Low level of inflammatory cytokine (IL-6(qualitative assay <100 pg/ml) lack of commitment to full aggressive care (anticipated withholding or withdrawing treatments in the first week) Immunocompromised (post-organ transplantation, HIV, neutropenic [<1000 PMN], steroids >20 mgs/day for 6 months). Chronic non-invasive ventilation (except if they become mechanically ventilated) Platelet count of < 30 GPt/L Pregnant patients. Urine/blood tests for pregnancy will be done on all women of childbearing age by each site as part of standard of ICU practice. Previous enrollment in this study Enrollment in other ICU intervention study Allergy to fish or fish oil (shellfish allergy not an exclusion criterion) Has already received enteral or IV omega-3 fatty acids during this hospitalization and current ICU admission.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard care<br>Standard care | |
| Active Comparator: standard care + 0.20gm/kg fish oil<br>standard care + 0.20gm/kg fish oil | Dietary Supplement: 0.20 gm/kg fish oil<br>* Group 2: 7 patients will receive 0.20gm/kg of ideal body weight [IBW] fish oil in addition to standard care<br>* Other names: Omegaven;|
| Active Comparator: standard care + 0.50 gm/kg fish oil<br>standard care + 0.50 gm/kg fish oil | Dietary Supplement: 0.50 gm/kg fish oil<br>* Group 3: 7 patients will receive 0.50 gm/kg of ideal body weight [IBW] fish oil in addition to standard care.<br>* Other names: Omegaven;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SOFA score | As the primary goal of this study is to establish the safety of high doses of IV fish oils, our primary outcomes will be change in SOFA score (organ function) and biochemical parameters of safety (i.e. blood lipid levels, coagulation parameters, bleeding episodes, standard biochemistry). | Day 1-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of systemic inflammation | Our secondary outcomes include markers of systemic inflammation [pro-calcitonin [PCT], C-reactive protein [CRP], interleukin-1 [IL-6] and IL-10) and markers of innate immunity [such as lipopolysaccharide [LPS] ex-vivo stimulation of tumor necrosis factor-alpha [TNF-α]]. | Day 1-10 | 
| Clinical outcomes | In addition, we plan to collect clinical outcomes such as ICU and hospital length of stay, number of infections, length of ventilation, and ICU, 28-day, and hospital mortality rate | Day 1-28 |