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.
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
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
Parallel
Ondansetron hydrochloride 8 mg IV Q8H
DrugParticipants 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 ml
DrugParticipants 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.
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.
Outcome data completeness
Data completeness for 90 day survival, 28 day ventilator-free days, and 14 day coma-and-delirium-free days.
Enrolment rate
Patients enrolled by site by 12-month period
Pmus
Pmus will be estimated by the occlusion pressure maneuvre, measured 3 times per day.
P0.1
P0.1 will be measured 3 times per day.
Respiratory Rate
Respiratory Rate will be measured 3 times per day.
Tidal volume
Tidal volume will be measured 3 times per day.
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