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

NCT07588217 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: MP-32-2026-3061
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ARDS (Acute Respiratory Distress Syndrome); Patient-Self Inflicted Lung Injury; Invasive Mechanical Ventilation

Keywords

ondansetron; 5HT3 antagonist; respiratory drive; respiratory effort

Outcome Measures

Primary Outcomes (1)

• protocol adherence

  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)

Secondary Outcomes (2)

• Outcome data completeness

  90 days

• Enrolment rate

  Duration of the study

Other Outcomes (13)

• Pmus

  duration of the intervention (duration of invasive mechanical ventilation)

• P0.1

  duration of the intervention (duration of invasive mechanical ventilation)

• Respiratory Rate

  duration of the intervention (duration of invasive mechanical ventilation)

Study Arms (2)

Ondansetron

EXPERIMENTAL

The first dose of intravenous ondansetron will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.

Drug: Ondansetron hydrochloride 8 mg IV Q8H

Placebo

PLACEBO COMPARATOR

The first dose of intravenous placebo will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.

Drug: 0.9 % Normal Saline 10 ml

Interventions

Ondansetron hydrochloride 8 mg IV Q8H DRUG

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.

Ondansetron

0.9 % Normal Saline 10 ml DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Hopital du Sacré-Coeur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

MeSH Terms

Conditions

Acute Lung Injury

Interventions

Ondansetron; Saline Solution

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virginie Williams, PhD

CONTACT

514-338-2222; eresi.cnmtl@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2026
• First Posted: May 14, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

CA (1)