Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

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

8 mai 2026 mis à jour par: 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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

76

Phase

  • Phase 2
  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • Hôpital du Sacré-Cœur de Montréal
        • Contact:
        • Chercheur principal:
          • Yiorgos Alexandros Cavayas, MD MSc

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Ondansetron
The first dose of intravenous ondansetron will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.
Médicament: 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.
Comparateur placebo: Placebo
The first dose of intravenous placebo will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.
Médicament: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
protocol adherence
Délai: 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)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Outcome data completeness
Délai: 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
Délai: Duration of the study
Patients enrolled by site by 12-month period
Duration of the study

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Pmus
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 90 days
Being alive at 90 days
90 days
Ventilator-Free Days
Délai: 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
Délai: 14 days
Number of days alive without delirium nor coma from any cause in the first 14 days
14 days

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

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

Les enquêteurs

  • Chercheur principal: 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
  • Chercheur principal: 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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 octobre 2026

Achèvement primaire (Estimé)

1 octobre 2028

Achèvement de l'étude (Estimé)

1 octobre 2029

Dates d'inscription aux études

Première soumission

8 mai 2026

Première soumission répondant aux critères de contrôle qualité

8 mai 2026

Première publication (Réel)

14 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

14 mai 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

8 mai 2026

Dernière vérification

1 mai 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • MP-32-2026-3061

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner