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

NCT00608322 | Completed Phase 3 Results DMC

• 2 other identifiers: K23GM0832111K23GM083211-01
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

Sepsis; Severe sepsis; Septic shock

Outcome Measures

Primary Outcomes (2)

• Change in the Sequential Organ Failure Assessment (SOFA) Score

  0-24 hours from protocol initiation

• Change in Sublingual Microcirculatory Flow Index (MFI)

  The MFI is a continuous scale from 0-3, with 3.0 being better outcome and 0.0 being worse outcome.

  0-2 hours of study drug administration

Secondary Outcomes (1)

• Lactate Clearance (Blood)

  0-2 hours of study drug administration

Study Arms (2)

1

EXPERIMENTAL

Subjects receive inhaled nitric oxide (40 parts per million) for six hours.

Drug: Inhaled nitric oxide

2

SHAM COMPARATOR

Subjects receive sham inhaled nitric oxide for six hours.

Other: Sham inhaled nitric oxide

Interventions

Inhaled nitric oxide DRUG

Inhaled nitric oxide, 40 parts per million, for six hours.

Also known as: INOmax

1

Sham inhaled nitric oxide OTHER

Sham inhaled nitric oxide administration, 0 parts per million, for six hours.

2

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of General Medical Sciences (NIGMS): lead

Study Sites (1)

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Related Publications (4)

• 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. doi: 10.1016/j.annemergmed.2006.08.021. Epub 2006 Nov 7.

  PMID: 17095120 BACKGROUND

• 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. doi: 10.1097/01.ccm.0000138558.16257.3f.

  PMID: 15343008 BACKGROUND

• 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. doi: 10.1056/NEJMoa010307.

  PMID: 11794169 BACKGROUND

• 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.

  PMID: 25080051 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Endothelium-Dependent Relaxing Factors

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Stephen Trzeciak, MD, MPH
• Organization: Cooper University Hospital

trzeciak-stephen@cooperhealth.edu

856-342-3342

Study Officials

• Stephen Trzeciak, MD, MPH

  UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, Camden, New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: January 23, 2008
• First Posted: February 6, 2008
• Study Start: August 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: July 11, 2013
• Results First Posted: July 11, 2013

Record last verified: 2013-06

Locations

US (1)