Acute Respiratory Distress Syndrome
Conditions
Keywords
ARDS, Ondansetron
Brief summary
This is a pilot study aimed at acquiring primary physiological data, describing and estimating the effects of a 5-HT3 receptor antagonist (ondansetron) on respiratory drive in patients with acute respiratory distress syndrome (ARDS). The results of this study will determine the interest and feasibility of assessing the clinical applications of ondansetron in reducing patient self-inflicted lung injury (P-SILI) in ARDS, in subsequent studies.
Interventions
DRUGPlacebo
Single intravenous dose of 10 mL of sodium chloride (NaCl) 0.9% over 15 minutes.
DRUGOndansetron
Single intravenous dose of ondansetron hydrochloride dihydrate 0.15 mg/kg (maximum 16 mg) in 10 mL of NaCl 0.9% over 15 minutes.
Sponsors
Fonds de la Recherche en Santé du Québec
Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
Because of the single sequence of administration, blinding of study personnel would not be possible. As the primary outcome is a continuously electronically recorded physiological parameter that does not require any human interpretation, single blinding should not result in any observation bias.
Intervention model description
Non-randomized crossover controlled trial with two interventions and one sequence. The sequence of treatment is first placebo and secondly ondansetron.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult patient (18-75 years old) * Berlin Criteria for Acute Respiratory Distress Syndrome (ARDS) (1): * Hypoxemic respiratory failure with a patrial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2 ratio) \< 300 * Bilateral opacities not fully explained by effusions, lung/lobar collapse, or nodules on chest imaging that appeared within 7 days of a known clinical insult * Respiratory failure not fully explained by cardiac failure or fluid overload * Has been mechanically ventilated \> 48 hours * Planned to remain mechanically ventilated for the next 24 hours * Currently on Pressure Support Ventilation or planning to go on pressure support ventilation in the next 24 hours
Exclusion criteria
* Having received a 5-HT3 antagonist in the last 24 hours, or planning to use one in the next 24 hours * Recently treated for bleeding varices, stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement * Severe coagulopathy (platelet count\< 10 000 or International Normalized Ratio (INR) \> 3) * Neuromuscular disease that impairs ability to ventilate spontaneously (including C5 or higher spinal cord injury, amyotrophic lateral sclerosis, Guillain-Barre syndrome or myasthenia gravis) * Treating clinician refusal, or unwillingness to commit to pressure support ventilation for at least 6 hours. * Pregnancy * Liver cirrhosis (Child B or C) or other severe impairment of hepatic function * Congestive heart failure * Bradyarrhythmia (baseline pulse\<55/min) * Known long QT syndrome * QTc prolongation\>450 msec, noted on prior or screening ECG, or who are taking medication known to cause QT prolongation * Hypersensitivity or other known intolerance to ondansetron or other 5-HT3 antagonists
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pressure-time product of the esophageal pressure per minute | Continuous measurement during each 2-hour phase | Difference in mean pressure-time product of the esophageal pressure per minute between placebo phase and ondansetron phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory rate | Continuous measurement during each 2-hour phase | Difference in mean respiratory rate between placebo phase and ondansetron phase |
| Tidal volume | Continuous measurement during each 2-hour phase | Difference in mean tidal volume between placebo phase and ondansetron phase |
| Pressure-time product of the esophageal pressure per breath | Continuous measurement during each 2-hour phase | Difference in mean pressure-time product of the esophageal pressure per breath between placebo phase and ondansetron phase |
| Esophageal pressure swings | Continuous measurement during each 2-hour phase | Difference in mean esophageal pressure swings between placebo phase and ondansetron phase |
| Transpulmonary pressure swings | Continuous measurement during each 2-hour phase | Difference in mean transpulmonary pressure swings between placebo phase and ondansetron phase |
| Estimated occlusion pressure at 0.1 msec (P0.1) | Continuous measurement during each 2-hour phase | Difference in mean estimated occlusion pressure at 0.1 msec (P0.1) between placebo phase and ondansetron phase |
| Peak electrical activity of the diaphragm (Eadi) | Continuous measurement during each 2-hour phase | Difference in mean peak Eadi between placebo phase and ondansetron phase |
| Area under the Eadi curve | Continuous measurement during each 2-hour phase | Difference in area under the Eadi curve between placebo phase and ondansetron phase |
| End-tidal CO2 (EtCO2) | Continuous measurement during each 2-hour phase | Difference in mean EtCO2 between placebo phase and ondansetron phase |
| Oxygen saturation estimated by pulse oximetry (SpO2) | Measurement every 5 minutes during each 2-hour phase | Difference in mean SpO2 between placebo phase and ondansetron phase |
| Partial pressure of carbon dioxide in arterial blood (PaCO2) | Measurement every 30 minutes during each 2-hour phase | Difference in mean PaCO2 between placebo phase and ondansetron phase |
| Partial pressure of oxygen in arterial blood (PaO2) | Measurement every 30 minutes during each 2-hour phase | Difference in mean PaO2 between placebo phase and ondansetron phase |
| Heart rate | Measurement every 5 minutes during each 2-hour phase | Difference in mean heart rate between placebo phase and ondansetron phase |
| Mean arterial pressure (MAP) | Measurement every 5 minutes during each 2-hour phase | Difference in mean MAP between placebo phase and ondansetron phase |
| Corrected QT length (QTc) | Measurement once (at the 1 hour-mark) during each 2-hour phase | Difference in QTc between placebo phase and ondansetron phase |
| Temperature | Hourly measurement during each 2-hour phase | Difference in mean temperature between placebo phase and ondansetron phase |
| Richmond Agitation and Sedation Scale (RASS) | Hourly measurement during each 2-hour phase | Difference in mean Richmond Agitation and Sedation Scale (RASS) between placebo phase and ondansetron phase. This scale goes from -5 (unraousable) to +4 (combative). |
| Critical care Pain Observation Tool (CPOT) | Hourly measurement during each 2-hour phase | Difference in mean Critical care Pain Observation Tool (CPOT) between placebo phase and ondansetron phase. This scale goes from 0 (lowest pain level) to 10 (highest pain level). |
| Volume of expired CO2 (VCO2) | Continuous measurement during each 2-hour phase | Difference in mean VCO2 between placebo phase and ondansetron phase |
Other
| Measure | Time frame | Description |
|---|---|---|
| Enrolment | Monthly through study completion (estimated 6 months) | Number of eligible patients and enrolled patients. |
Countries
Canada
Contacts
Primary ContactVirginie Williams
Outcome results
None listed