Clinical trial NCT01146821: Fish OIL Optimal dosE Determination Study
Official title: Multi-centre, Open-label, Phase II Clinical Trial for Determination of the Optimal Dose of Fish Oil in Patients With Severe Sepsis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sepsis
Lead sponsor: University Hospital Carl Gustav Carus
Sponsor class: OTHER
Collaborators: name: University of Giessen
name: Clinical Evaluation Research Unit at Kingston General Hospital
name: GWT-TUD GmbH
First posted: 2010-06-22
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in SOFA score
timeFrame: Day 1-10
Secondary outcomes:
measure: Markers of systemic inflammation
timeFrame: Day 1-10
measure: Clinical outcomes
timeFrame: Day 1-28
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Giessen
country: Germany
facility: University Hospital Giessen and Marburg
Study officials:
affiliation: University Hospital Dresden, Germany
name: Axel R. Heller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kingston General Hospital, Canada
name: Daren Heyland, MD, PhD
role: STUDY_CHAIR
affiliation: Kingston General Hospital, Canada
name: Rupinder Dhaliwal, RD
role: STUDY_DIRECTOR
References:
citation: Pradelli L, Mayer K, Muscaritoli M, Heller AR. n-3 fatty acid-enriched parenteral nutrition regimens in elective surgical and ICU patients: a meta-analysis. Crit Care. 2012 Oct 4;16(5):R184. doi: 10.1186/cc11668.
citation: Heller AR, Rossler S, Litz RJ, Stehr SN, Heller SC, Koch R, Koch T. Omega-3 fatty acids improve the diagnosis-related clinical outcome. Crit Care Med. 2006 Apr;34(4):972-9. doi: 10.1097/01.CCM.0000206309.83570.45.
citation: Heller AR, Rossel T, Gottschlich B, Tiebel O, Menschikowski M, Litz RJ, Zimmermann T, Koch T. Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients. Int J Cancer. 2004 Sep 10;111(4):611-6. doi: 10.1002/ijc.20291.
citation: Heller AR, Fischer S, Rossel T, Geiger S, Siegert G, Ragaller M, Zimmermann T, Koch T. Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery. Br J Nutr. 2002 Jan;87 Suppl 1:S95-101. doi: 10.1079/bjn2001462.
citation: Mayer K, Fegbeutel C, Hattar K, Sibelius U, Kramer HJ, Heuer KU, Temmesfeld-Wollbruck B, Gokorsch S, Grimminger F, Seeger W. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation. Intensive Care Med. 2003 Sep;29(9):1472-81. doi: 10.1007/s00134-003-1900-2. Epub 2003 Jul 25.
citation: Manzanares W, Dhaliwal R, Jurewitsch B, Stapleton RD, Jeejeebhoy KN, Heyland DK. Parenteral fish oil lipid emulsions in the critically ill: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr. 2014 Jan;38(1):20-8. doi: 10.1177/0148607113486006. Epub 2013 Apr 22.
citation: Pradelli L, Eandi M, Povero M, Mayer K, Muscaritoli M, Heller AR, Fries-Schaffner E. Cost-effectiveness of omega-3 fatty acid supplements in parenteral nutrition therapy in hospitals: a discrete event simulation model. Clin Nutr. 2014 Oct;33(5):785-92. doi: 10.1016/j.clnu.2013.11.016. Epub 2013 Dec 4.