Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Vicente Moran


Contact details

Intensive Care Department
Hospital de León
Altos de Nava
+34 98 72 37 400

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Effect of an enteral nutrition enriched with eicosapentaenoic acid, gamma-linolenic acid and anti-oxidants on the outcome of mechanically ventilated critically ill septic patients: a phase IV prospective multicentre randomised controlled parallel-group study


Study hypothesis

To determine whether an enteral diet enriched with gamma-linolenic acid, eicosapentaenoic acid and antioxidants is able to reduce the percentage of septic patients who develop at least one organic failure (new) during admission to the Intensive Care Unit (ICU) by at least a 20% (absolute terms) with respect to the control group (isocaloric and isonitrogenous standard enteral diet).

Ethics approval

Hospital de Leon Ethics Committee approved on the 9th December 2003 (ref: 33/03)

Study design

Phase IV prospective multicentre randomised simple-blind controlled parallel-group study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Systemic inflammatory response syndrome (SIRS)


Patient allocation:
Patients were randomly allocated to receive the control or the study product. A minimisation technique, where two stratification factors will be taken into account: site and severity of sepsis. Selected randomisation procedure guarantees that treatment arm cannot be predicted by the investigator.

The study product and comparator will be commercial products:
Control product: Isocaloric and isonitrogenous standard enteral diet. Commercial product: Ensure Plus HN in 500 mL RTH container (Ross Products Division of Abbott Laboratories, Spain)
Study product: A low-carbohydrate, calorically dense liquid food (containing EPA, GLA and antioxidants)
Commercial product: Oxepa (Ross Products Division of Abbott Laboratories, Spain) manufactured in Zwolle, The Netherlands for global distribution. Recommended rate for Oxepa is to begin full strength feeding at 20 - 30 ml/hr and increase by 10 ml every 8 hours until the goal rate is reached.

To calculate the total caloric daily intake to be given by EN, caloric needs were set 25 kcal/kg/day and protein intake of 1.5 g/kg/day, adjusting by ideal body weight for obese patients. Minimal required intake (at least 70% of the calculated dose) must be administered within 96 hours since the patient enters the study.

Enteral nutrition will be administered continuously with an infusion pump during 24 hours, through nasoenteral (gastric or pyloric) or transpiloric gavage. For its maintenance and efficacy, recommendations of the Nutritional and Metabolic Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units, published in the journals Medicina Intensiva and Nutrición Clínica, will be followed. These procedures have already been tested in two large epidemiological trials, the COMGINE trial and the ICOMEP, the second one not published yet. Both trials confirm homogeneity in EN procedures between the ICUs that will take part in the study.

Treatment duration:
The duration of treatment will be at least 5 days, counting from the time of randomisation until the end of the septic condition. The septic episode will be considered over when the patient does not meet the criteria for sepsis for 72 consecutive hours. No changes in regimen are considered during the study, except in cases of complications. All concomitant treatments (co-interventions) should be reflected in an easily legible manner for eventual review by the study monitor.

Transfusion policy:
Transfusion treatment is considered to be unrestricted and will be dealt with simply as another covariable (conventional versus restrictive transfusion). To this effect, the haemoglobin concentration prior to each transfusion will be recorded in the CRF.

The rest of supportive treatments usually used in daily care - including antibiotic or antifungal therapy and the different mechanical ventilation protocols - can be freely used according to criterion in each centre, though also in this case the CRF should document some variables of interest according to the prior experience of the group. The rest of supportive treatments are usually used in daily care, including antibiotics and vasoactive drugs, and the different mechanical ventilation protocols used followed the Survival Sepsis Campaign guidelines.

Intervention type



Phase IV

Drug names

Gamma linolenic acid, eicosapentaenoic acid, antioxidants

Primary outcome measure

Number of new organ failures during admission to the ICU measured by changes in delta-Sequential Organ Failure Assessment (SOFA) score, measured at days 1, 3, 7, 14 and 21.

Secondary outcome measures

1. Number of stays in the ICU
2. Number of days of mechanical ventilation
3. Incidence of nosocomial infection (incidence density) throughout the stay in the ICU
4. Overall all-cause mortality (cumulative incidence on day +28)
5. Overall mortality during admission to the ICU
6. Overall mortality on day +180 from admission to the ICU

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Eligible patients are defined as those subjects who satisfy ALL of the following:
1. Aged 18 years or older, either sex
2. A diagnosis of sepsis during admission to the ICU, without the provision of artificial nutrition in the minimum required amount
3. An indication for enteral nutrition
4. Patient registration in the Secretariat before the start of treatment
5. Informed consent for participation in the study

Participant type


Age group




Target number of participants


Participant exclusion criteria

Patients who present any of the following will NOT be eligible for inclusion in the study:
1. Established pregnancy
2. The reception of artificial nutrition in the 15 days prior to inclusion in the study
3. Known food allergy to any of the study diet components
4. Severe hyperlipidemia and hypertriglyceridemia
5. Gastrointestinal diseases precluding enteral nutrition (surgical resections, malabsorption, exacerbated inflammatory disease, persistent ileus, active upper digestive bleeding, etc.)
6. The impossibility of positioning the enteral nutrition tube
7. Immune depression, defined as:
7.1. Neutropenia (less than 1 x 10^9 neutrophils/l), or a prior diagnosis of myelodysplastic syndrome
7.2. Congenital immune deficiencies or acquired immune deficiency syndrome (AIDS) (Center for Disease Control and Prevention [CDC] criteria)
7.3. Systemic immunosuppressor therapy (including corticosteroids at prednisone equivalent doses of 1 mg/day or more) in the last 3 months
7.4. Systemic chemotherapy in the last 3 months
7.5. Autologous haematopoietic precursor cell transplantation in the previous year
7.6. Allogenic haematopoietic precursor cell transplantation in the last 2 years, or the existence of chronic graft versus host disease
8. Advanced chronic diseases:
8.1. Stage C chronic liver disease (Child Pugh)
8.2. Grade IV heart failure (New York Heart Association [NYHA])
8.3. Functional grade IV chronic respiratory failure
8.4. End stage degenerative neurological processes
8.5. End stage kidney failure
8.6. Neoplasms, either relapsing or in progression under treatment
9. Short life-expectancy processes:
9.1. Shock of any aetiology with multi-organ failure refractory to therapy in the first 48 hours
9.2. Fulminant acute hepatitis
9.3. Ischaemic haemorrhagic cerebrovascular accidents or head injuries with endocranial hypertension not controlled within 72 hours
9.4. Cardiogenic shock not overcome after 72 hours of specific treatment
9.5. Incoercible or recurrent serious acute haemorrhage for greater than 72 hours
9.6. Haemostatic disorders not controlled after 72 hours of specific treatment
9.7. Post-cardiopulmonary resuscitation with serious neurological damage 72 hours after arrest
10. Severe acute pancreatitis (except if infection is confirmed)
11. Administration of some experimental treatment in the past month, or present inclusion in another clinical study

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Intensive Care Department

Sponsor information


Spanish Society of Intensive Care (Sociedad Española de Medicina Intensiva) (Spain)

Sponsor details

Critica y Unidades Coronarias
Pso. Reina Cristina nº 36

Sponsor type

Research organisation



Funder type


Funder name

Abbott Laboratories (Spain) - provided freely to investigators the study and control products.

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

Please note Abbott Laboratories will not be involved in data acquisition, analysis and publication of this study. The final report will be jointly prepared by all the members of the Data Review and Publication Committee. Abbott Laboratories, S.A. will have the right to conduct a complementary analysis and express its point of view to the Committee through a representative - without this implying any restriction in the final decision of the mentioned control organism. The authorship criteria will be those currently considered by the Metabolism and Nutrition Work Group of the Spanish Society of Intensive Care Medicine. The conclusions of the study will be obligatorily submitted for publication - regardless of the results obtained.

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

1. 2006 results in
2. 2011 results in

Publication citations

  1. Results

    Pontes-Arruda A, Aragão AM, Albuquerque JD, Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock., Crit. Care Med., 2006, 34, 9, 2325-2333, doi: 10.1097/01.CCM.0000234033.65657.B6.

  2. Results

    Grau-Carmona T, Morán-García V, García-de-Lorenzo A, Heras-de-la-Calle G, Quesada-Bellver B, López-Martínez J, González-Fernández C, Montejo-González JC, Blesa-Malpica A, Albert-Bonamusa I, Bonet-Saris A, Herrero-Meseguer JI, Mesejo A, Acosta J, Effect of an enteral diet enriched with eicosapentaenoic acid, gamma-linolenic acid and anti-oxidants on the outcome of mechanically ventilated, critically ill, septic patients., Clin Nutr, 2011, 30, 5, 578-584, doi: 10.1016/j.clnu.2011.03.004.

Additional files

Editorial Notes