5-HT3 Receptor Antagonist and Respiratory Drive in Patients With ARDS

Phase 4

Recruiting

• Conditions: Acute Respiratory Distress Syndrome
• Interventions: Drug: Placebo; Drug: Ondansetron

• Registration Number: NCT05514483
• Lead Sponsor: Hopital du Sacre-Coeur de Montreal

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-17
• Study First Submitted QC: 2022-08-22
• Study First Posted: 2022-08-24
• Study Start: 2022-11-10
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-26
• Last Update Posted: 2023-09-28
• Primary Completion: 2024-03-06
• Study Completion: 2024-05-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.
Ondansetron	Ondansetron	All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Respiratory rate	Continuous measurement during each 2-hour phase	Difference in mean respiratory rate 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
Volume of expired CO2 (VCO2)	Continuous measurement during each 2-hour phase	Difference in mean VCO2 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
End-tidal CO2 (EtCO2)	Continuous measurement during each 2-hour phase	Difference in mean EtCO2 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
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).

Trial Locations

Locations (1)

Hôpital Sacré-Coeur de Montréal; 🇨🇦 Montréal, Quebec, Canada