Randomized Trial of Inhaled Nitric Oxide to Augment Tissue Perfusion in Sepsis

Study Description

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Brief Summary:

The purpose of this study is to determine whether inhaled nitric oxide is an effective treatment for microcirculatory dysfunction and acute organ system failure in the early stage of sepsis therapy.

Condition or disease	Intervention/treatment	Phase
Sepsis	Drug: Inhaled nitric oxide; Other: Sham inhaled nitric oxide	Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	49 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Randomized Double-blind Placebo-controlled Trial of Inhaled Nitric Oxide for the Treatment of Microcirculatory Dysfunction and Organ Failure in Sepsis
Study Start Date :	August 2009
Actual Primary Completion Date :	April 2013
Actual Study Completion Date :	April 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; Subjects receive inhaled nitric oxide (40 parts per million) for six hours.	Drug: Inhaled nitric oxide; Inhaled nitric oxide, 40 parts per million, for six hours.; Other Name: INOmax
Sham Comparator: 2; Subjects receive sham inhaled nitric oxide for six hours.	Other: Sham inhaled nitric oxide; Sham inhaled nitric oxide administration, 0 parts per million, for six hours.

Outcome Measures

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Primary Outcome Measures :

1. Change in the Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 0-24 hours from protocol initiation ]
2. Change in Sublingual Microcirculatory Flow Index (MFI) [ Time Frame: 0-2 hours of study drug administration ]
   The MFI is a continuous scale from 0-3, with 3.0 being better outcome and 0.0 being worse outcome.

Secondary Outcome Measures :

1. Lactate Clearance (Blood) [ Time Frame: 0-2 hours of study drug administration ]

Eligibility Criteria

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Ages Eligible for Study:	14 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Confirmed or suspected infection (acute)

   PLUS:

2. One or both of the following criteria for potential tissue hypoperfusion:

(2a) systolic blood pressure <90 mmHg despite 30cc/kg intravenous crystalloid challenge, OR (2b) serum lactate >4 mmol/L.

Exclusion Criteria:

1. age < 14 years
2. pregnancy
3. "Do Not Resuscitate" status (prior to enrollment)
4. active clinically significant bleeding of any etiology
5. status-post cardiac arrest
6. need for immediate surgery
7. inability to place a sublingual videomicroscopy probe under the tongue (e.g. inability to open the mouth or patient requirement of a high-flow face mask for supplemental oxygen [although videomicroscopy can be performed in patients with an endotracheal tube or nasal cannula])
8. >24 hours elapsed since first documented evidence of meeting criteria for potential tissue hypoperfusion (2a or 2b above).
9. inability to obtain written informed consent

Contacts and Locations

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Locations

United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103

Sponsors and Collaborators

National Institute of General Medical Sciences (NIGMS)

Investigators

Principal Investigator:	Stephen Trzeciak, MD, MPH	UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, Camden, New Jersey

More Information

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Publications:

Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, Arnold RC, Colilla S, Zanotti S, Hollenberg SM; Microcirculatory Alterations in Resuscitation and Shock Investigators. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007 Jan;49(1):88-98, 98.e1-2. Epub 2006 Nov 7.

Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004 Sep;32(9):1825-31.

Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Trzeciak S, Glaspey LJ, Dellinger RP, Durflinger P, Anderson K, Dezfulian C, Roberts BW, Chansky ME, Parrillo JE, Hollenberg SM. Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*. Crit Care Med. 2014 Dec;42(12):2482-92. doi: 10.1097/CCM.0000000000000549.

Responsible Party:	Dr. Trzeciak, PI, Cooper University Hospital
ClinicalTrials.gov Identifier:	NCT00608322 History of Changes
Other Study ID Numbers:	K23GM083211 ( U.S. NIH Grant/Contract ); 1K23GM083211-01 ( U.S. NIH Grant/Contract )
First Posted:	February 6, 2008
Results First Posted:	July 11, 2013
Last Update Posted:	July 11, 2013
Last Verified:	June 2013

Keywords provided by Dr. Trzeciak, Cooper University Hospital:

Sepsis; Severe sepsis; Septic shock

Additional relevant MeSH terms:

Sepsis; Toxemia; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Nitric Oxide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs	Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters; Protective Agents