Randomized Trial of Inhaled Nitric Oxide to Augment Tissue Perfusion in Sepsis - Full Text View

Purpose

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	Intervention	Phase
Sepsis	Drug: Inhaled nitric oxide Other: Sham inhaled nitric oxide	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Sepsis

Drug Information available for: Nitric oxide

U.S. FDA Resources

Further study details as provided by National Institute of General Medical Sciences (NIGMS):

Primary Outcome Measures:

Change in the Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 0-24 hours from protocol initiation ] [ Designated as safety issue: No ]
Change in Sublingual Microcirculatory Flow Index (MFI) [ Time Frame: 0-2 hours of study drug administration ] [ Designated as safety issue: No ]
The MFI is a continuous scale from 0-3, with 3.0 being better outcome and 0.0 being worse outcome.

Secondary Outcome Measures:

Lactate Clearance (Blood) [ Time Frame: 0-2 hours of study drug administration ] [ Designated as safety issue: No ]


Enrollment:	49
Study Start Date:	August 2009
Study Completion Date:	April 2013
Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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Eligibility


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

Criteria

Inclusion Criteria:

Confirmed or suspected infection (acute)

PLUS:
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:

age < 14 years
pregnancy
"Do Not Resuscitate" status (prior to enrollment)
active clinically significant bleeding of any etiology
status-post cardiac arrest
need for immediate surgery
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])
>24 hours elapsed since first documented evidence of meeting criteria for potential tissue hypoperfusion (2a or 2b above).
inability to obtain written informed consent

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608322

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

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 1K23GM083211-01
Study First Received:	January 23, 2008
Results First Received:	April 16, 2013
Last Updated:	June 3, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by National Institute of General Medical Sciences (NIGMS):


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

ClinicalTrials.gov processed this record on September 23, 2016