Early Versus Delayed Enteral Feeding to Treat People With Acute Lung Injury or Acute Respiratory Distress Syndrome (The EDEN Study) (EDEN)

Tracking Information
First Submitted Date ICMJE	April 17, 2009
First Posted Date ICMJE	April 20, 2009
Last Update Posted Date	April 13, 2016
Study Start Date ICMJE	December 2007
Actual Primary Completion Date	March 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 17, 2009)	Number of ventilator-free days (VFD) [ Time Frame: Measured at Day 28 ]; Mortality before hospital discharge, with unassisted breathing [ Time Frame: Measured at Days 60 and 90 ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00883948 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 17, 2009)	Number of intensive care unit-free days [ Time Frame: Measured at Day 28 ]; Number of organ failure-free days (liver, kidney, heart, central nervous system, and hematologic) [ Time Frame: Measured at Day 28 ]; Incidence of ventilator-associated pneumonia [ Time Frame: Measured at Day 28 ]; Number of days from first meeting criteria for weaning readiness to Day 28 [ Time Frame: Measured at Day 28 ]; VFDs and mortality in participants with a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FIO2) less than or equal to 200 or with shock at the time of study entry [ Time Frame: Measured at Days 28 and 60, respectively ]; Change in plasma and mini-bronchoalveolar lavage (BAL) levels of interleukin (IL)-6, IL-8, von Willebrand factor (VWF), surfactant protein D (SPD), and total protein concentrations [ Time Frame: Measured at Day 3 ]; Health-related quality of life; healthcare utilization; and psychological, neurocognitive, and physical activity outcomes [ Time Frame: Measured at Months 6 and 12 ]; Duration of survival after hospital discharge using the National Death Index [ Time Frame: Measured at Months 6 and 12 ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Early Versus Delayed Enteral Feeding to Treat People With Acute Lung Injury or Acute Respiratory Distress Syndrome (The EDEN Study)
Official Title ICMJE	Prospective, Randomized, Multi-Center Trial of Initial Trophic Enteral Feeding Followed by Advancement to Full-Calorie Enteral Feeding vs. Early Advancement to Full-Calorie Enteral Feeding in Patients With Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS)
Brief Summary	Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are medical conditions that occur when there is severe inflammation and increased fluids in both lungs, making it difficult for the lungs to function properly. Hospital treatment for a person with ALI/ARDS often includes the use of a breathing machine, or ventilator, until the person is able to breathe without assistance. Initiating proper nutrition through a feeding tube early in a person's hospital stay may help to improve recovery, but the optimal timing, composition, and amount of feeding treatments remain unknown. This study will evaluate whether early or delayed full-calorie feeding through a feeding tube is more effective in reducing recovery time and increasing survival rates in people with ALI/ARDS.
Detailed Description	ALI/ARDS involves extensive inflammation in the lungs that can lead to rapid respiratory failure. These conditions are most commonly caused by pneumonia, generalized infection, or severe trauma to the lungs, but can also be less commonly caused by smoke or salt water inhalation, drug overdose, or shock. For some people, ALI/ARDS resolves without treatment, but many severe cases result in hospitalization in the intensive care unit (ICU), where 30% to 40% of cases end in mortality. Current treatments for ALI/ARDS include assisted breathing with a ventilator, supportive care, and management of the underlying causes. Enteral feeding, in which patients receive nutrition through a feeding tube, plays an important role in treatment, too. Some recent studies have shown that enteral feeding initiated soon after a patient begins assisted breathing is associated with a shorter hospital stay and a better chance of survival than delayed enteral feeding. However, other studies have shown the opposite, and studies on optimal feeding volume and composition have shown conflicting results. This study will evaluate the effects of early versus delayed full-calorie enteral feeding on mortality, ventilator-free days, ICU-free days, and organ failure in people with ALI/ARDS. Upon admission to the ICU, a dietary evaluation will be done on each participant to determine goal, or full-calorie, feeding rates, which will be based on body weight and daily energy consumption. Participants will also undergo baseline assessments and procedures, which will include vital sign measurements, blood draws, a frontal chest radiograph, ventilator settings, and placement of a feeding tube. Participants will be randomly assigned to receive initial enteral feedings that are either minimal (trophic) or full-calorie. All participants will begin enteral feeding within 6 hours of treatment assignment. Participants assigned to initial minimal enteral feedings will receive feedings at 10 cubic centimeters (cc) per hour, to be continued at this rate for 144 hours, provided that the participant remains on the ventilator. After the 144 hours, the feeding rate will be advanced to full-calorie rates. Participants assigned to initial full-calorie enteral feedings will receive feedings at 25 cc per hour, and the feeding rate will be increased by 25 cc per hour every 6 hours until the goal rate is reached. During enteral feedings, gastric residual volumes (GRVs) will be checked every 6 to 12 hours to assure acceptable levels. Participants will complete enteral feedings upon hospital discharge, Day 28 of treatment, death, or ability to achieve 48 hours of unassisted breathing. Blood pressure, heart rate, ventilation settings, and various blood factors will be measured during treatment. Phone-based follow-up assessments will occur at Months 6 and 12 after ICU discharge and will include measurements of health-related quality of life; psychological, neurocognitive, and physical activity outcomes; healthcare utilization; and mortality.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Respiratory Distress Syndrome, Adult
Intervention ICMJE	Behavioral: Minimal (Trophic) Feeding Upon admission to the ICU, enteral feeds will be started at 10 cc per hour and continued at this rate for 144 hours. After 144 hours of trophic enteral feeds, the feeding rate will be advanced to full-calorie rates, which will continue for the duration of mechanical ventilation up to Day 28.; Behavioral: Full Feeding Upon admission to the ICU, a full-calorie feeding rate will be determined, which will be calculated to deliver 25 to 35 kcal/kg predicted body weight (PBW) each day. Enteral feeds will be initiated at 25 cc per hour. The feeding rate will be increased by 25 cc per hour every 6 hours until goal rate is achieved, which will be administered for the duration of mechanical ventilation up to Day 28.
Study Arms	Experimental: 1 Participants will receive initial minimal (trophic) enteral feeding. Intervention: Behavioral: Minimal (Trophic) Feeding; Experimental: 2 Participants will receive initial full-calorie enteral feeding. Intervention: Behavioral: Full Feeding
Publications *	Brown SM, Wilson E, Presson AP, Zhang C, Dinglas VD, Greene T, Hopkins RO, Needham DM; with the National Institutes of Health NHLBI ARDS Network. Predictors of 6-month health utility outcomes in survivors of acute respiratory distress syndrome. Thorax. 2017 Apr;72(4):311-317. doi: 10.1136/thoraxjnl-2016-208560. Epub 2016 Jul 20.; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, Dong N, Rock P. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012 Feb 22;307(8):795-803. doi: 10.1001/jama.2012.137. Epub 2012 Feb 5.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 17, 2009)	1000
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	May 2011
Actual Primary Completion Date	March 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Must meet the following three criteria within a 24-hour period of study entry: 1) PaO2/FiO2 less than or equal to 300 (if altitude is more than 1000 meters, then PaO2/FiO2 less than or equal to 300 x [barometric pressure/760]), 2) bilateral infiltrates (patchy, diffuse, homogeneous, or asymmetric) consistent with pulmonary edema on frontal chest radiograph, and 3) requirement for positive pressure ventilation via endotracheal tube; No clinical evidence of left-sided cardiac failure to account for bilateral pulmonary infiltrates; Intention of primary medical team to enterally feed the patient; Undergoes enteral feeding within 48 hours of meeting other inclusion criteria Exclusion Criteria: Neuromuscular disease that impairs ability to breathe without assistance, such as cervical spinal cord injury at level C5 or higher, amyotrophic lateral sclerosis, Guillain-Barré syndrome, or myasthenia gravis; Pregnant or breastfeeding; Severe chronic respiratory disease (more information about this criterion can be found in the protocol); Burns on greater than 40% total body surface area; Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50% (more information about this criterion can be found in the protocol); Allogeneic bone marrow transplant in the 5 years before study entry; Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest); Severe long-term liver disease (Child-Pugh score of 11 to 15); Diffuse alveolar hemorrhage from vasculitis; Morbid obesity, defined as 1 kg/cm body weight; Unwilling or unable to use the ARDS network 6 mL/kg PBW ventilation protocol; Moribund patient not expected to survive 24 hours after study entry; No intent to obtain central venous access for monitoring intravascular pressures; More than 72 hours since mechanical ventilation initiated; Refractory shock (more information about this criterion can be found in the protocol); Unable to obtain enteral access; Presence of partial or complete mechanical bowel obstruction; Presence of ischemia or infarction; Current total parenteral nutrition (TPN) use or intent to use TPN within 7 days of study entry; Severe malnutrition with body mass index less than 18.5 or loss of more than 30% total body weight in the 6 months before study entry; Laparotomy expected within 7 days of study entry; Unable to raise head of bed 30 to 45 degrees; Short-bowel syndrome or absence of gastrointestinal tract; Presence of high-output (greater than 500 cc/day) enterocutaneous fistula; International normalized ratio greater than 5.0, platelet count less than 30,000/mm3, or history of bleeding disorder; Intracranial hemorrhage in the 1 month before study entry; Allergy to enteral formula; Requirement for, or physician insistence on, enteral formula supplemented with omega-3 fatty acids (e.g., Oxepa®, Impact®) or treatment with omega-3 fatty acid, gamma-linolenic acid (GLA), or antioxidant supplementation
Sex/Gender	Sexes Eligible for Study: All
Ages	13 Years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00883948
Other Study ID Numbers ICMJE	651; N01-HR056179, HSN268200536179C
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Heart, Lung, and Blood Institute (NHLBI)
Study Sponsor ICMJE	National Heart, Lung, and Blood Institute (NHLBI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Arthur P. Wheeler, MD Vanderbilt University Medical Center
PRS Account	National Heart, Lung, and Blood Institute (NHLBI)
Verification Date	February 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP