ARDS (Acute Respiratory Distress Syndrome)Phase 2/3OSIRIS-1NCT07588217
Ondansetron for the Prevention of Patient Self-Inflicted Lung Injury in Patients With ARDS - Pilot RCT
A Phase 2/3 study testing Ondansetron hydrochloride 8 mg IV Q8H and 0.9 % Normal Saline 10 ml in people with ARDS (Acute Respiratory Distress Syndrome) and Invasive Mechanical Ventilation, run by Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ARDS (Acute Respiratory Distress Syndrome), Invasive Mechanical Ventilation, Patient-Self Inflicted Lung Injury
- What is being tested?
- Ondansetron hydrochloride 8 mg IV Q8H and 0.9 % Normal Saline 10 ml
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteCanada
- Study dates
- 1 Oct 2026to 1 Oct 2029
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
Hopital du Sacré-Coeur de Montréal
Montreal, Quebec, H4J 1C5
Virginie Williams, PhD, 514-338-2222 ext. 5833272, eresi.cnmtl@ssss.gouv.qc.ca
Yiorgos Alexandros Cavayas, MD MSc
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- ARDS (Acute Respiratory Distress Syndrome), Invasive Mechanical Ventilation, Patient-Self Inflicted Lung Injury
- Being tested
- Ondansetron hydrochloride 8 mg IV Q8H, 0.9 % Normal Saline 10 ml
- Keywords
- ondansetron, 5HT3 antagonist, respiratory drive, respiratory effort
- Medical subject headings
- Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ondansetron hydrochloride 8 mg IV Q8HDrug
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.
0.9 % Normal Saline 10 mlDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 0.9 % Normal Saline 10 ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: duration of intervention (duration of invasive mechanical ventilation)
Secondary outcomes (2)
Outcome data completeness
Data completeness for 90 day survival, 28 day ventilator-free days, and 14 day coma-and-delirium-free days.
Measured: 90 days
Enrolment rate
Patients enrolled by site by 12-month period
Measured: Duration of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ARDS (Acute Respiratory Distress Syndrome)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yiorgos Alexandros Cavayas, MD MSc, Principal investigator, Centre Intégré Universitaire de Santé et Services Sociaux du Nord-de-l'Ile-de-Montréal - Hôpital du Sacré-Coeur de MontréalDavid Williamson, BPharm, PhD, Principal investigator, Centre Intégré Universitaire de Santé et Services Sociaux du Nord-de-l'Ile-de-Montréal - Hôpital du Sacré-Coeur de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07588217
- Sponsor's protocol ID
- MP-32-2026-3061
- Acronym
- OSIRIS-1
- Status last verified
- May 2026
- First submitted
- 8 May 2026
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided