NCT02425579

Brief Summary

The purpose of this study is to assess the safety of inhaled carbon monoxide (iCO) in intubated patients with sepsis-induced ARDS.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2015

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 17, 2015

Completed
15 days until next milestone

Study Start

First participant enrolled

April 1, 2015

Completed
23 days until next milestone

First Posted

Study publicly available on registry

April 24, 2015

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2019

Completed
Last Updated

October 17, 2019

Status Verified

October 1, 2019

Enrollment Period

4.3 years

First QC Date

March 17, 2015

Last Update Submit

October 15, 2019

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Outcome Measures

Primary Outcomes (2)

  • Number of administration associated adverse events.

    1. Acute myocardial infarction (MI) within 48 hours of study drug administration 2. Acute cerebrovascular accident (CVA) within 48 hours of study drug administration 3. New onset atrial or ventricular arrhythmia requiring direct current (DC) cardioversion within 48 hours of study drug administration 4. Increased oxygenation requirements defined as: an increase in fraction of inspired oxygen (FiO2) of greater than or equal to 0.2 AND increase in PEEP greater than or equal to 5 cm of water (H2O) within 6 hours of study drug administration 5. Increase in any protocol-specified measurement of carboxyhemoglobin (COHb) greater than or equal to 10% 6. Increase in lactate by greater than or equal to 2 mmol/L within 6 hours of study drug administration

    60 Days if remains in the ICU

  • Incidence of serious adverse events (SAEs).

    An SAE is any event that is fatal or immediately life threatening, is permanently disabling, or severely incapacitating, or requires or prolongs inpatient hospitalization. Important medical events that may not result in death, be life threatening, or require hospitalization may be considered SAEs when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed above.

    60 Days if remains in the ICU

Secondary Outcomes (9)

  • Comparison between the calculated carboxyhemoglobin (COHb) level at 90 minutes using the Coburn-Forster-Kane (CFK) equation and measured COHb level at 90 minutes

    5 days

  • Mean daily Sequential Organ Failure Assessment (SOFA) score

    7 days

  • Partial pressure of arterial oxygen (PaO2)/FiO2 ratio

    5 days

  • Oxygenation index (OI)

    5 days

  • Lung injury score (LIS)

    7 Days

  • +4 more secondary outcomes

Other Outcomes (1)

  • Plasma biomarkers of inflammation, lung epithelial injury,endothelial injury, markers of change in other end-organ function

    5 days

Study Arms (4)

Cohort 1

EXPERIMENTAL

Inhaled Carbon Monoxide at 100 ppm for up to 90 minutes daily for 5 days

Drug: Inhaled Carbon Monoxide at 100ppm (4 participants)

Cohort 1 (placebo)

PLACEBO COMPARATOR

Inhaled Medical Air for up to 90 minutes daily for 5 days

Drug: Placebo for Inhaled Carbon Monoxide at 100ppm (2 participants)

Cohort 2

EXPERIMENTAL

Inhaled Carbon Monoxide at 200 ppm for up to 90 minutes daily for 5 days

Drug: Inhaled Carbon Monoxide at 200ppm (4 participants)

Cohort 2 (Placebo)

PLACEBO COMPARATOR

Inhaled Medical Air for up to 90 minutes daily for 5 days

Drug: Placebo for Inhaled Carbon Monoxide at 200ppm (2 participants)

Interventions

Inhaled Carbon Monoxide at 100ppm (4 participants)DRUG

Inhaled Carbon Monoxide at 100ppm for up to 90 minutes daily for 5 days

Also known as: iCO
Cohort 1
Placebo for Inhaled Carbon Monoxide at 100ppm (2 participants)DRUG

Inhaled Medical Air for up to 90 minutes daily for 5 days

Also known as: Inhaled Medical Air
Cohort 1 (placebo)
Inhaled Carbon Monoxide at 200ppm (4 participants)DRUG

Inhaled Carbon Monoxide at 200ppm for 90 minutes daily for 5 days

Also known as: iCO
Cohort 2
Placebo for Inhaled Carbon Monoxide at 200ppm (2 participants)DRUG

Inhaled Medical Air for up to 90 minutes daily for 5 days

Also known as: Inhaled Medical Air
Cohort 2 (Placebo)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with sepsis are defined as those with suspected or documented infection:
  • Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and central nervous system
  • All eligible patients meet the new definition of sepsis (suspected or proven infection and a SOFA ≥ 2) as PaO2/FiO2 ratio \< 300 = 2 SOFA points.
  • ARDS is defined when all four of the following criteria are met:
  • A PaO2/FiO2 ratio ≤ 300 with at least 5 cm H2O positive end-expiratory airway pressure (PEEP)
  • Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
  • A need for positive pressure ventilation by an endotracheal or tracheal tube
  • No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.
  • ARDS onset is defined as the time the last of criteria 1-4 are met. ARDS must persist through the enrollment time window of 120 hours.
  • Infiltrates considered "consistent with pulmonary edema" include any infiltrates not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (greater than 1 week). Vascular redistribution, indistinct vessels, and indistinct heart borders alone are not considered "consistent with pulmonary edema" and thus would not count as qualifying opacities for this study.

You may not qualify if:

  • Age less than 18 years
  • Greater than 120 hours since ARDS onset
  • Pregnant or breast-feeding
  • Prisoner
  • 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)
  • No consent/inability to obtain consent
  • Physician refusal to allow enrollment in the trial
  • Moribund patient not expected to survive 24 hours
  • No arterial line/no intent to place an arterial line
  • No intent/unwillingness to follow lung protective ventilation strategy
  • Severe hypoxemia defined as oxygenation saturation (SpO2) \<95 or PaO2 \<80 on FiO2 ≥0.8
  • Hemoglobin \< 7.5 g/dl or hemoglobin \< 8 g/dl and actively bleeding
  • Subjects who are Jehovah's Witnesses or are otherwise unable or unwilling to receive blood transfusions during hospitalization
  • Acute myocardial infarction (MI) or acute coronary syndrome (ACS) within the last 90 days
  • Coronary artery bypass graft (CABG) surgery within 30 days
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Weill Cornell Medical College/NewYork-Presbyterian

New York, New York, 10065, United States

Location

Duke Univesity Hospital

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

  • Fredenburgh LE, Perrella MA, Barragan-Bradford D, Hess DR, Peters E, Welty-Wolf KE, Kraft BD, Harris RS, Maurer R, Nakahira K, Oromendia C, Davies JD, Higuera A, Schiffer KT, Englert JA, Dieffenbach PB, Berlin DA, Lagambina S, Bouthot M, Sullivan AI, Nuccio PF, Kone MT, Malik MJ, Porras MAP, Finkelsztein E, Winkler T, Hurwitz S, Serhan CN, Piantadosi CA, Baron RM, Thompson BT, Choi AM. A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS. JCI Insight. 2018 Dec 6;3(23):e124039. doi: 10.1172/jci.insight.124039.

    PMID: 30518685DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration Disorders

Study Officials

  • Laura E Fredenburgh, MD

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D.

Study Record Dates

First Submitted

March 17, 2015

First Posted

April 24, 2015

Study Start

April 1, 2015

Primary Completion

August 1, 2019

Study Completion

August 1, 2019

Last Updated

October 17, 2019

Record last verified: 2019-10

Data Sharing

IPD Sharing
Will not share

Locations

US(4)