Early Insulin and Development of ARDS

• ClinicalTrials.gov Identifier: NCT00605696
• Recruitment Status: Completed
• First Posted: January 31, 2008
• Results First Posted: April 10, 2017
• Last Update Posted: May 7, 2018
• Sponsor: Albert Einstein College of Medicine
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Michelle Gong, Albert Einstein College of Medicine

Study Description

Brief Summary:

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is a severe lung condition that causes respiratory failure. Symptoms usually develop within 24 to 48 hours of an original injury or illness, and people with ALI/ARDS typically require care in the intensive care unit (ICU). Little is known about how to prevent the onset of ALI/ARDS. The purpose of this study is to examine if early infusions of insulin, known as intensive insulin therapy (IIT), can help prevent ALI/ARDS in hospitalized patients with high levels of blood sugars and severe infections.

Condition or disease	Intervention/treatment	Phase
Respiratory Distress Syndrome, Adult; Sepsis; Hyperglycemia	Drug: Insulin	Phase 2

Detailed Description:

ALI/ARDS is a life-threatening condition that involves inflammation of the lungs and fluid accumulation in the air sacs, leading to low blood oxygen levels and respiratory failure. Common causes include pneumonia, lung trauma, and sepsis, a condition that can lead to widespread inflammation and blood clotting in response to an infection. Recent studies have shown that insulin, which is regularly used to control blood sugar levels, may prevent or lessen the risk of lung tissue inflammation and/or lung injury related to sepsis. Research has shown that critically ill ICU patients often benefit from receiving insulin to target 80-110 mg/dl , but it is not known if insulin to target these levels can prevent the onset of ALI/ARDS. Therapies to prevent ALI/ARDS should occur early, preferably even prior to ICU admission, because at least 38% of people with ALI/ARDS are diagnosed with the condition once they reach the ICU. The purpose of this study is to determine whether insulin to target 80-110 mg/dl administered to critically ill patients in the emergency department (ED) is more beneficial at preventing ALI/ARDS than insulin to target 150-180 mg/dl after ICU admission.

This study will enroll people who are hospitalized with high blood sugar levels and severe sepsis. Participants will be randomly assigned to receive IIT within 6-12 hours of ED presentation to target 80-110 mg/dl or target 150-180 mg/dl for 48 hours after admission to the ICU followed by usual care. Prior to ICU admission and 1, 3, and 7 days after ICU admission, blood will be collected and analyzed for markers of inflammation and lung injury. Blood samples will be stored for future research studies. While participants are in the hospital, their medical records will be reviewed to gather information on medical and family history, demographics, vital signs, laboratory test results, x-ray findings, and lung function. Study researchers will also monitor participants for the development of severe lung failure or other organ failures.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Early Insulin Therapy and Development of Acute Respiratory Distress Syndrome
• Study Start Date: April 2008
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: September 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Participants will receive insulin to target glucose 80-110 mg/dl within 6-12 hours after presenting to ED.	Drug: Insulin; Participants will receive intravenous insulin to target tight glycemic control (80 to 110 mg/dL) for up to 48 hours after ICU admission.
Active Comparator: 2; Participants will receive insulin to target 150-180 mg/dl for 48 hours after ICU admission followed by usual clinical care.	Drug: Insulin; Participants will receive intravenous insulin to target tight glycemic control (80 to 110 mg/dL) for up to 48 hours after ICU admission.

Outcome Measures

Primary Outcome Measures :

1. Plasma Levels of Free Fatty Acids, Tumor Necrosis Factor-α, Interleukin-6, and Von Willebrand Factor Antigen [ Time Frame: Measured at Day 1, 3 and 7 ]

Secondary Outcome Measures :

1. Murray Lung Injury Score [ Time Frame: Measured at Day 3 ]
   Murray Lung Injury Score is a continuous score that quantifies the severity of lung injury and consist of components related to severity of hypoxia, pulmonary compliance, peep, and radiologic abnormalities. The scores range between 0 - 4. The higher the score, the greater the degree and severity of lung injury. The scale runs from 0-4, with 0 being the minimum and 4 the maximum score.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosed with severe sepsis, which is defined as sepsis AND one or more signs of organ dysfunction or hypotension
• Hyperglycemia (i.e., glucose level greater than 130 mg/dL on one or more tests)

Exclusion Criteria:

• Diabetic ketoacidosis
• Severe chronic liver disease with Child-Pugh score greater than 10 (Class C)
• Documented episodes of blood or plasma glucose less than 60 mg/dL within 24 hours of study entry
• Lack of any available IV access for insulin infusion
• Pregnant
• Known advanced directives against intubation or aggressive ICU care
• Inability to be enrolled into the study in the 12 hours following admission to the ED

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Sponsors and Collaborators

Albert Einstein College of Medicine

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Michelle Ng Gong, MD, MS; Montefiore Medical Center

More Information

• Responsible Party: Michelle Gong, Associate Professor, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT00605696
• Other Study ID Numbers: 2009-462; R01HL086667 ( U.S. NIH Grant/Contract )
• First Posted: January 31, 2008
• Results First Posted: April 10, 2017
• Last Update Posted: May 7, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Michelle Gong, Albert Einstein College of Medicine:

Acute Respiratory Distress Syndrome; Acute Lung Injury

Additional relevant MeSH terms:

Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Hyperglycemia; Syndrome; Disease; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Glucose Metabolism Disorders; Metabolic Diseases; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs