Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

Ondansetron for the Prevention of Patient Self-Inflicted Lung Injury in Patients With ARDS - Pilot RCT (OSIRIS-1)

8. Mai 2026 aktualisiert von: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

A Pilot, Randomized, Controlled Clinical Trial Evaluating Ondansetron for the Prevention of Patient Self-Inflicted Lung Injury Through Inhibition of Respiratory Drive in Patients With Acute Respiratory Distress Syndrome (OSIRIS-1)

Acute Respiratory Distress Syndrome (ARDS) is a serious condition where the lungs become inflamed, leading to severe breathing difficulties. Despite advances in medical care, ARDS remains a life-threatening illness with a high risk of death and long-term complications. One way doctors help ARDS patients is by using special ventilation techniques to protect the lungs from further damage. However, this often requires heavy sedation or even paralyzing medications, which can lead to other problems like delirium, muscle weakness, and longer hospital stays. Allowing patients to breathe on their own might offer benefits, but it also comes with risks. Many ARDS patients have a very strong urge to breathe, which can cause them to overexert their lungs, potentially leading to additional lung damage, known as patient selfinflicted lung injury (P-SILI). Our early research suggests that a medication called ondansetron, commonly used to prevent nausea, might help reduce this strong breathing drive in ARDS patients, possibly preventing further lung injury. The OSIRIS research program is designed to explore whether ondansetron can protect ARDS patients from P-SILI, ultimately improving their chances of survival and reducing long-term complications. The first part of this program, OSIRIS-1, is a small pilot study where we will test the feasibility of running a larger, more definitive trial. We will randomly assign ARDS patients to receive either ondansetron or a placebo, given intravenously four times a day, and monitor their heart rhythms closely to ensure safety. We will also track how well patients stick to the study plan and whether ondansetron helps reduce their breathing drive and lung strain. If successful, this research could lead to new ways of treating ARDS that rely less on heavy sedation, potentially improving outcomes for these critically ill patients and setting the stage for larger, more comprehensive studies in the future.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening inflammatory lung condition with high mortality and long-term morbidity. Lung-protective ventilation - targeting low tidal volumes and driving pressures - is one of the few proven interventions but often requires deep sedation and neuromuscular blockade (NMB), which are associated with delirium, ICU-acquired weakness, and prolonged ICU stays. Maintaining spontaneous breathing can offer physiological advantages but is frequently limited by excessive respiratory drive, which increases the risk of patient self-inflicted lung injury (P-SILI). Lung inflammation leading to stimulation and sensitization of pulmonary vagal afferent Cfibers could contribute to excessive respiratory effort. Stimulation of pulmonary C-fibers by serotonin increases respiratory rate in animal models through 5-HT receptors. Our previous data suggest that 3 ondansetron, a 5-HT receptor antagonist, attenuates respiratory drive and effort. We hypothesize that 3 this effect may reduce the need for sedation and paralysis, minimize P-SILI, and ultimately improve outcomes in ARDS.

OBJECTIVES: The overarching goal of the OSIRIS research program is to evaluate whether regular intravenous ondansetron can improve patient-important outcomes (survival, ventilator-free days and long term neurocognitive function) in patients with ARDS. With the OSIRIS-1 pilot study, our objective is to assess:

Feasibility:

[RQ1] What is the adherence to the study protocol? [PRIMARY] [RQ2] What is the completeness of the data collection? [RQ3] What is the recruitment rate?

Preliminary mechanistic efficacy and safety:

[RQ4] Does it decrease respiratory effort? [RQ5] Does it reduce exposure to sedatives, opioids and neuromuscular blockers? [RQ6] Is the intervention safe?

METHODS: OSIRIS-1 is a multicenter, double-blind, parallel-group, phase 2 and feasibility pilot RCT. We will enroll 76 invasively mechanically ventilated adults with moderate-to-severe ARDS (PaO :FiO2 < 200). Participants will be randomized to receive ondansetron 8 mg IV or placebo every 8 hours until liberation from invasive mechanical ventilation. Feasibility will be assessed through protocol adherence (defined as scheduled doses administered within ±2 hours), completeness of key clinical outcomes (ventilator-free days, coma/delirium-free days, 90-day survival), and site-level recruitment metrics. For preliminary efficacy, we will estimate respiratory drive using Pmus (derived from occlusion pressure, ΔPocc), measured three times daily by respiratory therapists. We will also measure P0.1, respiratory rate, and other ventilatory parameters. For safety, we will monitor the occurrence of ventricular arrhythmias, serotonin syndrome, and other serious adverse events.

IMPACT: OSIRIS-1 will provide essential data on mechanistic efficacy, safety, and feasibility to inform the design of a future large-scale trial evaluating patient-important outcomes. By targeting respiratory drive pharmacologically, we may enable safer spontaneous breathing, reduce the harms of oversedation and paralysis, and ultimately improve outcomes in ARDS.

Studientyp

Interventionell

Einschreibung (Geschätzt)

76

Phase

  • Phase 2
  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

  • Kanada
    • Quebec
      • Montreal, Quebec, Kanada, H4J 1C5
        • Hopital du Sacre-Coeur de Montreal
        • Kontakt:
        • Hauptermittler:
          • Yiorgos Alexandros Cavayas, MD MSc

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene
  • Älterer Erwachsener

Akzeptiert gesunde Freiwillige

Nein

Beschreibung

Inclusion Criteria:

  • Moderate-to-severe ARDS with all of the following:
  • Hypoxemic respiratory failure with PaO2:FiO2 < 200 (on IMV with PEEP ≥ 5)
  • Precipitated within 1 week of an acute condition
  • Bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on ultrasound not fully explained by effusions, atelectasis, or nodules/masses
  • Pulmonary edema not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload
  • Hypoxemia/gas exchange abnormalities not primarily attributable to atelectasis
  • IMV initiated < 96 hours
  • Extubation not anticipated within 24 hours

Exclusion Criteria:

  • Neuromuscular disease impairing spontaneous breathing
  • Pregnancy
  • Liver cirrhosis (Child B or C) or other severe impairment of hepatic function
  • Bradycardia (baseline pulse<50/min) on screening day
  • Known long QT syndrome
  • History of sustained ventricular tachycardia
  • Active digestive / abdominal infection44
  • QTc prolongation > 470 msec in men and > 480 msec in women on screening day
  • On a medication at high risk of QT prolongation (Table 5)50
  • On two or more serotonergic medications (Table 6)51
  • Hypersensitivity / intolerance to 5-HT3 antagonists
  • Patient deemed unlikely to survive past 24 hours or being transitioned to a fully palliative philosophy of care

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Ondansetron
The first dose of intravenous ondansetron will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.
Arzneimittel: Ondansetron hydrochloride 8 mg IV Q8H
Participants randomized to the ondansetron arm will receive ondansetron hydrochloride dihydrate 8 mg IV every 8 hours, administered in 10 mL of 0.9% sodium chloride in prepared syringes over 15 minutes.
Placebo-Komparator: Placebo
The first dose of intravenous placebo will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.
Arzneimittel: 0.9 % Normal Saline 10 ml
Participants randomized to the placebo arm will receive 10 mL of 0.9% sodium chloride in prepared syringes administered over 15 minutes every 8 hours, matching the appearance, volume, and administration modalities of ondansetron to maintain blinding.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
protocol adherence
Zeitfenster: duration of intervention (duration of invasive mechanical ventilation)
Adherence will be measured as the proportion of scheduled doses (±2h window) administered; protocol-defined withholdings (e.g., electrophysiological disturbances) will be documented but not counted as non-adherence.
duration of intervention (duration of invasive mechanical ventilation)

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Outcome data completeness
Zeitfenster: 90 days
Data completeness for 90 day survival, 28 day ventilator-free days, and 14 day coma-and-delirium-free days.
90 days
Enrolment rate
Zeitfenster: Duration of the study
Patients enrolled by site by 12-month period
Duration of the study

Andere Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Pmus
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
Pmus will be estimated by the occlusion pressure maneuvre, measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
P0.1
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
P0.1 will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
Respiratory Rate
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
Respiratory Rate will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
Tidal volume
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
Tidal volume will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
PaO2:FiO2 ratio
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
PaO2:FiO2 ratio will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
Number of days of deep sedation
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
A deep sedation will be defined as a day in which a Richmond Agitation and Sedation Scale (RASS) of -4 or -5 was present for the majority of the day
duration of the intervention (duration of invasive mechanical ventilation)
Average daily oral morphine equivalent
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
All opiates received during a given day will be converted in oral morphine equivalent and summed up.
duration of the intervention (duration of invasive mechanical ventilation)
Days with NMB administration
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
Defined by having received any dose or neuromuscular blocker during a given day.
duration of the intervention (duration of invasive mechanical ventilation)
Sustained Ventricular Arrhythmia
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
Defined as ventricular tachycardia or fibrillation sustained for ≥30 seconds or requiring termination due to hemodynamic compromise in <30 seconds.
duration of the intervention (duration of invasive mechanical ventilation)
Serotonin Syndrome
Zeitfenster: duration of the intervention (duration of invasive mechanical ventilation)
Serotonin syndrome (ie, serotonin toxicity) is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities.
duration of the intervention (duration of invasive mechanical ventilation)
90-day survival
Zeitfenster: 90 days
Being alive at 90 days
90 days
Ventilator-Free Days
Zeitfenster: 28 days
Number of days alive and free of mechanical ventilation in the first 28 days with death before day 28 counted as 0
28 days
Coma-and-delirium-free days
Zeitfenster: 14 days
Number of days alive without delirium nor coma from any cause in the first 14 days
14 days

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Ermittler

  • Hauptermittler: Yiorgos Alexandros Cavayas, MD MSc, Centre Intégré Universitaire de Santé et Services Sociaux du Nord-de-l'Ile-de-Montréal - Hôpital du Sacré-Coeur de Montréal
  • Hauptermittler: David Williamson, BPharm, PhD, Centre Intégré Universitaire de Santé et Services Sociaux du Nord-de-l'Ile-de-Montréal - Hôpital du Sacré-Coeur de Montréal

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. Oktober 2026

Primärer Abschluss (Geschätzt)

1. Oktober 2028

Studienabschluss (Geschätzt)

1. Oktober 2029

Studienanmeldedaten

Zuerst eingereicht

8. Mai 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

8. Mai 2026

Zuerst gepostet (Tatsächlich)

14. Mai 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

14. Mai 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

8. Mai 2026

Zuletzt verifiziert

1. Mai 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • MP-32-2026-3061

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

UNENTSCHIEDEN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Klinische Studien zur ARDS (akutes Atemnotsyndrom)

Klinische Studien zur Ondansetron hydrochloride 8 mg IV Q8H

Suchen Sie nach ähnlichen Studien

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

CROs by country

CROs in Burkina Faso

Bedingungen

Seltene Krankheiten

Drogeninterventionen

Nahrungsergänzungsmittel

Sponsor / Mitarbeiter

Standorte

Abonnieren