Clinical trial NCT05514483: 5-HT3 Receptor Antagonist and Respiratory Drive in Patients With ARDS
Official title: Effect of a 5-HT3 Receptor Antagonist on Respiratory Drive in Spontaneously Breathing Mechanically Ventilated Patients With Acute Respiratory Distress Syndrome (ARDS): a Pilot Proof-of-concept Crossover Non-randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Respiratory Distress Syndrome
Keywords: ARDS
Ondansetron
Lead sponsor: Hopital du Sacre-Coeur de Montreal
Sponsor class: OTHER
Collaborators: name: Fonds de la Recherche en Santé du Québec
First posted: 2022-08-24
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Non-randomized crossover controlled trial with two interventions and one sequence. The sequence of treatment is first placebo and secondly ondansetron.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pressure-time product of the esophageal pressure per minute
timeFrame: Continuous measurement during each 2-hour phase
Secondary outcomes:
measure: Respiratory rate
timeFrame: Continuous measurement during each 2-hour phase
measure: Tidal volume
timeFrame: Continuous measurement during each 2-hour phase
measure: Pressure-time product of the esophageal pressure per breath
timeFrame: Continuous measurement during each 2-hour phase
measure: Esophageal pressure swings
timeFrame: Continuous measurement during each 2-hour phase
measure: Transpulmonary pressure swings
timeFrame: Continuous measurement during each 2-hour phase
measure: Estimated occlusion pressure at 0.1 msec (P0.1)
timeFrame: Continuous measurement during each 2-hour phase
measure: Peak electrical activity of the diaphragm (Eadi)
timeFrame: Continuous measurement during each 2-hour phase
measure: Area under the Eadi curve
timeFrame: Continuous measurement during each 2-hour phase
measure: End-tidal CO2 (EtCO2)
timeFrame: Continuous measurement during each 2-hour phase
measure: Volume of expired CO2 (VCO2)
timeFrame: Continuous measurement during each 2-hour phase
measure: Oxygen saturation estimated by pulse oximetry (SpO2)
timeFrame: Measurement every 5 minutes during each 2-hour phase
measure: Partial pressure of carbon dioxide in arterial blood (PaCO2)
timeFrame: Measurement every 30 minutes during each 2-hour phase
measure: Partial pressure of oxygen in arterial blood (PaO2)
timeFrame: Measurement every 30 minutes during each 2-hour phase
measure: Heart rate
timeFrame: Measurement every 5 minutes during each 2-hour phase
measure: Mean arterial pressure (MAP)
timeFrame: Measurement every 5 minutes during each 2-hour phase
measure: Corrected QT length (QTc)
timeFrame: Measurement once (at the 1 hour-mark) during each 2-hour phase
measure: Temperature
timeFrame: Hourly measurement during each 2-hour phase
measure: Richmond Agitation and Sedation Scale (RASS)
timeFrame: Hourly measurement during each 2-hour phase
measure: Critical care Pain Observation Tool (CPOT)
timeFrame: Hourly measurement during each 2-hour phase
Other outcomes:
measure: Enrolment
timeFrame: Monthly through study completion (estimated 6 months)
Locations:
city: Montréal
country: Canada
facility: Hôpital Sacré-Coeur de Montréal
state: Quebec
Study officials:
affiliation: Hopital du Sacré Coeur de Montréal, Centre de recherche du centre intégré universitaire de santé et services sociaux du Nord-de-l'Ile-de-Montréal
name: Yiorgos Alexandros Cavayas, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References: