Acute Respiratory Distress Syndrome
Conditions
Keywords
ARDS, Parenteral, Pharmaconutrition
Brief summary
The purpose of this study is to evaluate the effects of nutritional supplementation with omega-9 olive-oil and omega-6 soybean oil based lipid emulsions in the Acute Respiratory Distress Syndrome (ARDS). The investigators hypothesize that these specific lipids in combination will immunomodulate the inflammatory reaction that occurs in the lungs of ARDS subjects. This concept is known as Pharmaconutrition. These lipids will be given intravenously so as to assure administration and only as a supplement to enteral nutrition which all subjects will also receive. The omega-9 will be compared to the omega-6 formulation which is the only FDA approved formulation of use in the United States since its development in 1961 by Fresenius-Kabi, Bad Homburg, Germany. The investigators plan to perform a bronchoscopy with lavage within 24 hours of enrollment, begin the lipid administration and continue it for 96 hours after which time the investigators will repeat bronchoscopy with lavage to assess changes. The lipid administration will cease following the second bronchoscopy. The fluid obtained from lavage combined with serum samples obtained at the time of bronchoscopy will be analyzed for inflammatory mediators and cell counts. Clinical data tracing will include but not be limited to: ventilator days, nutritional status, ICU time, oxygenation and lung compliance, and 30-day mortality.
Interventions
DRUGClinOleic 20%
96 hour continuous infusion.
DRUGIntralipid 20%
96 hour continuous infusion.
Sponsors
Methodist Research Institute, Indianapolis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* diagnosed with predisposing condition causing ARDS * are mechanically ventilated through an endotracheal tube * have enteral feeding access * have central venous access * have a PaO2:FiO2 ratio of less than 200 * have bilateral pulmonary infiltrates on chest x-ray
Exclusion criteria
* sedation requiring the use of diprivan (after enrollment) * a clinical diagnosis of left ventricular failure * lung cancer * hematologic malignancy * severe dyslipidemia * condition precluding bronchoscopy including inability to maintain oxygen saturations greater than 90% per pulse oximetry despite conventional mechanical ventilation * severe immunosuppression * use of NSAIDS within previous 24 hours * HIV positive * pregnancy * hypersensitivity to egg or soybean oil * active myocardial infarction * acute pancreatitis if complicated by hypertriglyceridemia * severe sepsis with 2 or more organ failures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Bronchoalveolar Lavage Fluid Interleukin-8 Concentrations | 96 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PaO2:FiO2 Ratio | 4 days | PaO2:FiO2 ratio at time of 2nd Bronchoalveolar Lavage (BAL) or end of study drug administration. |
| 30 Day Mortality | 30 days | — |
| New Infection | 30 days | We will use standard clinical criteria including but not limited to: fever, pyuria, new inflitrate on chest x-ray, positive blood cultures, abscess detected on imaging, leukocytosis, and positive skin or soft-tissue cultures to identify presence of new bacterial infections occurring after enrollment. |
| Organ Failures | 30 days | — |
| Ventilator Days | 30 days | — |
| Hospital Length of Stay | 30 days | — |
| Allergic Reactions | 96 hours | — |
| Hypertriglyceridemia | 96 hours | Defined as triglyceride level \>400 |
| Biomarkers (C-reactive Protein) | 96 hours | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental ClinOleic 20% Patients received dietary supplement with ClinOleic 20%. | 7 |
| Control: Intralipid 20% Patients received dietary supplement with Intralipid 20%. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Experimental ClinOleic 20% | Total | Control: Intralipid 20% |
|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 11.24 | 62 years STANDARD_DEVIATION 12.66 | 60 years STANDARD_DEVIATION 14.55 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 12 Participants | 5 Participants |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 10 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 7 | 1 / 7 |
| serious Total, serious adverse events | 1 / 7 | 1 / 7 |
Outcome results
Primary
Bronchoalveolar Lavage Fluid Interleukin-8 Concentrations
Time frame: 96 hours
Population: Each arm has one less subject than specified in the participate flow module. One is secondary to the fact that the subject refused the 2nd bronchoscopy and the other is because the primary physician felt the subject was too sick to undergo the 2nd bronchscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental ClinOleic 20% | Bronchoalveolar Lavage Fluid Interleukin-8 Concentrations | 1092 pg/mL | Standard Deviation 1017 |
| Control: Intralipid 20% | Bronchoalveolar Lavage Fluid Interleukin-8 Concentrations | 544 pg/mL | Standard Deviation 453.6 |
Secondary
30 Day Mortality
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental ClinOleic 20% | 30 Day Mortality | 1 participants |
| Control: Intralipid 20% | 30 Day Mortality | 1 participants |
Secondary
Allergic Reactions
Time frame: 96 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental ClinOleic 20% | Allergic Reactions | 0 participants |
| Control: Intralipid 20% | Allergic Reactions | 0 participants |
Secondary
Biomarkers (C-reactive Protein)
Time frame: 96 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental ClinOleic 20% | Biomarkers (C-reactive Protein) | 10 mg/L | Standard Deviation 9.06 |
| Control: Intralipid 20% | Biomarkers (C-reactive Protein) | 13 mg/L | Standard Deviation 13.81 |
Secondary
Hospital Length of Stay
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental ClinOleic 20% | Hospital Length of Stay | 22 days | Standard Deviation 8.45 |
| Control: Intralipid 20% | Hospital Length of Stay | 28 days | Standard Deviation 19.78 |
Secondary
Hypertriglyceridemia
Defined as triglyceride level \>400
Time frame: 96 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental ClinOleic 20% | Hypertriglyceridemia | 0 participants |
| Control: Intralipid 20% | Hypertriglyceridemia | 0 participants |
Secondary
New Infection
We will use standard clinical criteria including but not limited to: fever, pyuria, new inflitrate on chest x-ray, positive blood cultures, abscess detected on imaging, leukocytosis, and positive skin or soft-tissue cultures to identify presence of new bacterial infections occurring after enrollment.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental ClinOleic 20% | New Infection | 1 participants |
| Control: Intralipid 20% | New Infection | 0 participants |
Secondary
Organ Failures
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental ClinOleic 20% | Organ Failures | 1 participants |
| Control: Intralipid 20% | Organ Failures | 1 participants |
Secondary
PaO2:FiO2 Ratio
PaO2:FiO2 ratio at time of 2nd Bronchoalveolar Lavage (BAL) or end of study drug administration.
Time frame: 4 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental ClinOleic 20% | PaO2:FiO2 Ratio | 159 mmHg | Standard Deviation 60.8 |
| Control: Intralipid 20% | PaO2:FiO2 Ratio | 149 mmHg | Standard Deviation 78.44 |
Secondary
Ventilator Days
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental ClinOleic 20% | Ventilator Days | 18 days | Standard Deviation 10.11 |
| Control: Intralipid 20% | Ventilator Days | 18 days | Standard Deviation 11.34 |