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Sikkerheds- og effektivitetsundersøgelse af inhaleret kulilte til behandling af akut respiratorisk distress-syndrom (ARDS)

15. juni 2026 opdateret af: Rebecca Baron, Brigham and Women's Hospital

Et fase II-forsøg med inhaleret kulilte til behandling af akut respiratorisk distress-syndrom (ARDS)

Dette studie vil være et multicenter, prospektivt, randomiseret, delvist dobbeltblindt, placebokontrolleret fase II klinisk forsøg med inhaleret CO (iCO) til behandling af ARDS. Forsøget vil blive udført på 7 medicinske centre for tertiær pleje, herunder Weill Cornell Medicine/NewYork-Presbyterian Hospital, Brigham and Women's Hospital (BWH), Massachusetts General Hospital (MGH), Duke University Hospital, Durham Veterans Administration Medical Center, New York-Presbyterian Brooklyn Methodist Hospital og Duke Regional Hospital. Formålet med denne undersøgelse er at evaluere sikkerheden, tolerabiliteten og effektiviteten af ​​inhaleret kulilte (iCO) til behandling af ARDS og at undersøge de biologiske udlæsninger af lavdosis iCO-terapi hos patienter med ARDS

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Akut respiratorisk distress syndrom (ARDS) er en ødelæggende sygdom, der påvirker militære, veteraner og civile befolkninger. ARDS er et syndrom af alvorlig akut lungebetændelse og hypoxæmisk respirationssvigt med en forekomst på 180.000 tilfælde årligt i USA. På trods af de seneste fremskridt inden for intensivbehandling og lungebeskyttende ventilationsstrategier forbliver ARDS-morbiditet og -dødelighed uacceptabelt høj. Manglen på specifikke effektive terapier til ARDS indikerer et behov for nye behandlinger, der retter sig mod nye veje. Kulilte (CO) repræsenterer en ny terapeutisk modalitet i ARDS baseret på data opnået i eksperimentelle modeller af ARDS i løbet af det seneste årti.

CO har vist sig at være beskyttende i eksperimentelle modeller af akut lungeskade (ALI) og sepsis. Ydermere har flere humane undersøgelser vist, at eksperimentel administration af flere forskellige koncentrationer af CO tolereres godt, og at lavdosis inhaleret CO sikkert kan administreres til forsøgspersoner i et kontrolleret forskningsmiljø. Efterforskerne har tidligere udført et fase I-forsøg med lavdosis iCO i ARDS, som viste, at præcis administration af lavdosis iCO (100 og 200 ppm) er mulig, veltolereret og sikker hos patienter med sepsis-induceret ARDS.

Formålet med denne undersøgelse er at vurdere sikkerheden og effektiviteten af ​​lavdosis inhaleret kulilte (iCO) behandling hos mekanisk ventilerede patienter med ARDS.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

4

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, Forenede Stater, 02114
        • Massachusetts General Hospital
    • Missouri
      • St Louis, Missouri, Forenede Stater, 63130
        • Washington University
    • New York
      • Brooklyn, New York, Forenede Stater, 11215
        • New York-Presbyterian Brooklyn Methodist Hospital
      • New York, New York, Forenede Stater, 10065
        • Weill Cornell Medical College
    • North Carolina
      • Durham, North Carolina, Forenede Stater, 27710
        • Duke University Hospital
      • Durham, North Carolina, Forenede Stater, 27704
        • Duke Regional Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

14 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

Alle intuberede patienter ≥ 18 år med ARDS

  1. ARDS er defineret, når alle fire af følgende kriterier er opfyldt:

    1. Et PaO2/FiO2-forhold ≤ 300 med mindst 5 cm H2O positivt end-ekspiratorisk luftvejstryk (PEEP)
    2. Bilateral opacitet på frontalt røntgenbillede af thorax (ikke fuldt ud forklaret af effusioner, lobar/lungekollaps eller knuder) inden for 1 uge efter en kendt klinisk fornærmelse eller nye eller forværrede luftvejssymptomer
    3. Et behov for overtryksventilation med en endotracheal- eller trachealtube
    4. Åndedrætssvigt ikke fuldt ud forklaret af hjertesvigt eller væskeoverbelastning; har brug for objektiv vurdering (f.eks. ekkokardiografi) for at udelukke hydrostatisk ødem, hvis der ikke er nogen risikofaktor til stede.
  2. ARDS-debut er defineret som det tidspunkt, hvor det sidste af kriterierne 1-4 er opfyldt. ARDS skal bestå gennem tilmeldingstidsvinduet på 168 timer.

Ekskluderingskriterier:

En person, der opfylder et af følgende kriterier, vil blive udelukket fra deltagelse i denne undersøgelse:

  1. Alder under 18 år
  2. Mere end 168 timer siden ARDS debut
  3. Gravid eller ammende
  4. Fange
  5. Patient, surrogat eller læge, der ikke er forpligtet til fuld støtte (undtagelse: en patient vil ikke blive udelukket, hvis han/hun ville modtage al støttende behandling med undtagelse af forsøg på genoplivning fra hjertestop)
  6. Intet samtykke/manglende evne til at opnå samtykke eller passende juridisk repræsentant ikke tilgængelig
  7. Lægen nægtede at tillade optagelse i retssagen
  8. Døende patient forventes ikke at overleve 24 timer
  9. Ingen arteriel eller central linje/ingen hensigt om at placere en arteriel eller central linje
  10. Ingen hensigt/uvilje til at følge lungebeskyttende ventilationsstrategi
  11. Alvorlig hypoxæmi defineret som SpO2 < 95 eller PaO2 < 90 på FiO2 ≥ 0,9
  12. Hæmoglobin < 7,0 g/dL
  13. Forsøgspersoner, der er Jehovas Vidner eller på anden måde ikke er i stand til eller uvillige til at modtage blodtransfusioner under indlæggelse
  14. Akut myokardieinfarkt (MI) eller akut koronarsyndrom (ACS) inden for de sidste 90 dage
  15. Koronararterie-bypass-operation (CABG) inden for 30 dage
  16. Angina pectoris eller brug af nitrater med daglige aktiviteter
  17. Hjerte-lungesygdom klassificeret som NYHA klasse IV
  18. Slagtilfælde (iskæmisk eller hæmoragisk) inden for den foregående 1 måned, hjertestop, der kræver CPR inden for de foregående 72 timer, eller manglende evne til at vurdere mental status efter hjertestop
  19. Forbrændinger > 40 % total kropsoverflade (TBSA)
  20. Alvorlig inhalationsskade i luftvejene
  21. Brug af højfrekvent oscillerende ventilation
  22. Brug af ekstrakorporal membraniltning (ECMO)
  23. Samtidig brug af inhaleret pulmonal vasodilatorbehandling (f. nitrogenoxid [NO] eller prostaglandiner)
  24. Diffus alveolær blødning fra vaskulitis
  25. Samtidig deltagelse i anden lægemiddelundersøgelse

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Inhaleret kulilte
Inhaleret kulilte ved 200 ppm i op til 90 minutter dagligt i 3 dage.
Medicin: Inhaleret kulilte ved 200 ppm
Inhaleret kulilte ved 200 ppm i 90 minutter dagligt i 3 dage.
Andre navne:
  • iCO
Placebo komparator: Medicinsk luft
Inhaleret medicinsk luft i op til 90 minutter dagligt i 3 dage.
Andet: Indåndet medicinsk luft
Inhaleret medicinsk luft i op til 90 minutter dagligt i 3 dage.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Primary Safety Outcome: Number of Pre-specified Administration-related Adverse Events.
Tidsramme: 7 days

Safety of inhaled CO, defined by the incidence of pre-specified administration-related AEs (as defined below) and spontaneously reported AEs through study day 7.

  1. Acute 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 DC cardioversion within 48 hours of study drug administration
  4. Increased oxygenation requirements defined as: an increase in FiO2 of ≥ 0.2 AND increase in PEEP ≥ 5 cm H2O within 6 hours of study drug administration
  5. Increase in COHb ≥ 10%
  6. Increase in lactate by ≥ 2 mmol/L within 6 hours of study drug administration
7 days
Primary Efficacy Outcome: Change in Mitochondrial DNA (mtDNA) Level From Day 1 to Day 5
Tidsramme: 5 days
Mitochondrial DNA (mtDNA) plasma levels will be measured by quantitative PCR of human NADH dehydrogenase 1. The number presented is the percentage average difference from beginning to end of treatment. Limited number of measurements prevents variance analyses; therefore we present the data from the subjects available in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
5 days

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Lung Injury Score (LIS) on Days 1-5, and on Days 1-7
Tidsramme: 7 days
The Lung Injury Score (LIS) is a composite 4-point scoring system including the PaO2/FiO2, PEEP, quasi-static respiratory compliance, and the extent of infiltrates on the chest X-ray. Each of the four components is categorized from 0 to 4, where a higher number is worse. The total Lung Injury Score is obtained by dividing the aggregate sum by the number of components used. Previous randomized clinical trials in ARDS have shown that a decreased LIS correlates with improvement in lung physiology as well as important clinical outcomes including mortality and ventilator-free days (VFDs). The number presented is the average difference from beginning to end of treatment. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
7 days
Percent Change in PaO2/FiO2 Ratio on Days 1-5, and on Days 1-7
Tidsramme: 7 days
PaO2/FiO2 will be measured daily on days 1-5 and days 1-7 in ventilated subjects. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
7 days
Percent Change in Oxygenation Index (OI) on Days 1-5, and Days 1-7
Tidsramme: 7 days
The oxygenation index will be measured on days 1-5 and on days 1-7 in ventilated subjects. Oxygenation index is calculated as (FiO2 X mean airway pressure)/PaO2. We provide change in Oi from baseline. Oi is only measured when subjects are ventilated, therefore not all timepoints are available. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
7 days
Percent Change in Dead Space Fraction (Vd/Vt) on Days 1-3, and Days 1-7
Tidsramme: 7 days
The dead space fraction will be measured days 1-3 and days 1-7 in ventilated subjects. We present change in dead space fraction between initial and final measurements that were available (measurements only taken while the subjects were intubated). The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
7 days
Percent Change in Sequential Organ Failure Assessment (SOFA) Score on Days 1-5, and Days 1-7.
Tidsramme: 1-5 and 1-7 days
Organ failure will be assessed using the SOFA score. SOFA scores will be assessed daily on days 1-5 and day 7, as the SOFA score has been shown to be a reliable prognostic indicator of outcomes in critically ill patients. To calculate the Sequential Organ Failure Assessment (SOFA) score, each of the six components (Respiratory, Coagulation, Liver, Cardiovascular, Central Nervous System, Renal) is categorized from 0-4, where a higher number is worse. The SOFA score (0-24) will be calculated by summing all six components. We present changes in SOFA score over the time of hospitalization, over the time of ICU admission (up to days 5 and 7 for the enrolled subjects). The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
1-5 and 1-7 days
Absolute Value of Biomarkers of Inflammation and Inflammasome Activation
Tidsramme: 4 days
Cytokine plasma levels (eg. IL-1B) will be measured by ELISA daily on days 1-3 and on day 4. We report the absolute Mean Fluorescent Intensity (MFI) of each sample at pretreatment time point of day 4. Limited number of measurements prevents variance and measures of dispersion analyses; therefore we present the data from the subjects available in each group and report as "Number" without standard deviation, since measures of dispersion cannot be calculated.
4 days
Percent Change in Lipid Mediators
Tidsramme: 4 days
Lipid mediators (LM) and specialized pro-resolving mediators (SPMs) will be measured in plasma using liquid chromatography-tandem mass spectrometry (LC-MS-MS) based methods daily on days 1-3 and on day 4. The percentage change from baseline at day 1 to post treatment at day 4 is reported. A representative LM is shown (14-HDHA (14-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid) is an oxidized metabolite of omega-3 docosahexaenoic acid (DHA)). Limited number of measurements prevents variance and measures of dispersion analyses; therefore we present the data from the subjects available in each group and report as "Number" without standard deviation, since measures of dispersion cannot be calculated.
4 days

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Ventilator-free Days at Day 28
Tidsramme: 28 days
Ventilator-free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
28 days
ICU-free Days at Day 28
Tidsramme: 28 days
ICU-free days are the number of days that the patient is alive and free from ICU care within 28 days. Is calculated by subtracting the total number of days that the patient is free from the ICU from 28. Patients who die within 28 days are automatically assigned "0" ICU free days. We present data of ICU free days for enrolled subjects. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
28 days
Hospital-free Days at Day 60
Tidsramme: 60 days
Hospital-free days will be assessed on day 60. Hospital-free days are days alive post hospital discharge through day 60. Patients who die on or prior to day 60 are assigned zero hospital-free days. We present hospital free days at day 60. The limited number of measurements prevent the variance and measures of dispersion calculations; therefore we present the average of data from the available subjects in each group and report as "Mean" without standard deviation, where measures of dispersion cannot be calculated.
60 days
Hospital Mortality to Day 28 and 60
Tidsramme: 60 days
Mortality will be assessed on day 28 and day 60
60 days
Montreal Cognitive Assessment- MoCA-Blind
Tidsramme: 6 months
Montreal Cognitive Assessment - Blind Version (MoCA-Blind) The MoCA-Blind is a remote adaptation of the Montreal Cognitive Assessment (MoCA) used as a screening assessment for detecting cognitive impairment. It is administered via telephone interview. The MoCA-Blind assesses the following cognitive domains (points): - Attention (0-6) - Language: (0-3 (Repetition (0-2) and fluency (0-1)) - Abstraction (0-2) - Memory: Delayed recall (0-5) - Orientation (0-6) The minimum score is 0 and maximum score is 22 points. Calculated as the sum of all domains. Interpretation: Higher scores indicate better cognitive functioning. Lower scores indicate worse cognitive functioning (greater cognitive impairment). A score of 18 or above is within the normal range. Limited number of measurements prevents variance and measures of dispersion analyses; therefore we present the data from the subjects available in each group and report as "Number", since given measures of dispersion cannot be calculated.
6 months
Hayling Sentence Completion Test
Tidsramme: 6 months
The Hayling Sentence Completion Test assesses executive functioning (response initiation and inhibition), administered via telephone. With 30 sentence-completion items split into 2 sections (15 each). Sections: - 1: Response initiation (time to provide a contextually appropriate word). - 2: Response inhibition (time and error score for providing an unrelated word). Scores (response time and errors) from both sections are combined and converted to an age-adjusted standardized total score. Total combined standardized score ranges from 1-10: 1: Impaired 2: Abnormal 3: Poor 4: Low Average 5: Moderate Average 6: Average 7: High Average 8: Good 9: Superior 10: Very Superior Higher scores= Better executive functioning Lower scores= Greater impairment. Limited number of measurements prevents variance and measures of dispersion analyses; therefore we present the data from the subjects available in each group and report as "Number", since given measures of dispersion cannot be calculated.
6 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Brigham and Women's Hospital

Samarbejdspartnere

Massachusetts General Hospital
Washington University School of Medicine
Duke University
Weill Medical College of Cornell University
U.S. Army Medical Research Acquisition Activity
Durham VA Medical Center
New York Presbyterian Brooklyn Methodist Hospital
Duke Regional Hospital

Efterforskere

  • Ledende efterforsker: Rebecca Baron, MD, Brigham and Women's Hospital

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

30. september 2019

Primær færdiggørelse (Faktiske)

13. april 2021

Studieafslutning (Faktiske)

13. april 2021

Datoer for studieregistrering

Først indsendt

6. december 2018

Først indsendt, der opfyldte QC-kriterier

9. januar 2019

Først opslået (Faktiske)

10. januar 2019

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. juni 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2018P002051
  • CDMRP-PR171025, W81XWH1810667 (Andet bevillings-/finansieringsnummer: United States Army Medical Research Acquisition Activity)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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