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

Acute Respiratory Distress Syndrome Clinical Trial

— DRIVE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05514483
• Other study ID #: 2023-2502
• Status: Recruiting
• Phase: Phase 4
• Start date: November 10, 2022
• Est. completion date: May 6, 2024

Study information

• Verified date: September 2023
• Source: Hopital du Sacre-Coeur de Montreal
• Contact: Virginie Williams
• Phone: 514-338-2222
• Email: virginie.williams.cnmtl[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: May 6, 2024
• Est. primary completion date: March 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Placebo
Single intravenous dose of 10 mL of sodium chloride (NaCl) 0.9% over 15 minutes.
• Ondansetron
Single intravenous dose of ondansetron hydrochloride dihydrate 0.15 mg/kg (maximum 16 mg) in 10 mL of NaCl 0.9% over 15 minutes.

Locations

Country	Name	City	State
Canada	Hôpital Sacré-Coeur de Montréal	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Hopital du Sacre-Coeur de Montreal	Fonds de la Recherche en Santé du Québec

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Enrolment	Number of eligible patients and enrolled patients.	Monthly through study completion (estimated 6 months)
Primary	Pressure-time product of the esophageal pressure per minute	Difference in mean pressure-time product of the esophageal pressure per minute between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Respiratory rate	Difference in mean respiratory rate between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Tidal volume	Difference in mean tidal volume between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Pressure-time product of the esophageal pressure per breath	Difference in mean pressure-time product of the esophageal pressure per breath between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Esophageal pressure swings	Difference in mean esophageal pressure swings between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Transpulmonary pressure swings	Difference in mean transpulmonary pressure swings between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Estimated occlusion pressure at 0.1 msec (P0.1)	Difference in mean estimated occlusion pressure at 0.1 msec (P0.1) between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Peak electrical activity of the diaphragm (Eadi)	Difference in mean peak Eadi between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Area under the Eadi curve	Difference in area under the Eadi curve between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	End-tidal CO2 (EtCO2)	Difference in mean EtCO2 between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Volume of expired CO2 (VCO2)	Difference in mean VCO2 between placebo phase and ondansetron phase	Continuous measurement during each 2-hour phase
Secondary	Oxygen saturation estimated by pulse oximetry (SpO2)	Difference in mean SpO2 between placebo phase and ondansetron phase	Measurement every 5 minutes during each 2-hour phase
Secondary	Partial pressure of carbon dioxide in arterial blood (PaCO2)	Difference in mean PaCO2 between placebo phase and ondansetron phase	Measurement every 30 minutes during each 2-hour phase
Secondary	Partial pressure of oxygen in arterial blood (PaO2)	Difference in mean PaO2 between placebo phase and ondansetron phase	Measurement every 30 minutes during each 2-hour phase
Secondary	Heart rate	Difference in mean heart rate between placebo phase and ondansetron phase	Measurement every 5 minutes during each 2-hour phase
Secondary	Mean arterial pressure (MAP)	Difference in mean MAP between placebo phase and ondansetron phase	Measurement every 5 minutes during each 2-hour phase
Secondary	Corrected QT length (QTc)	Difference in QTc between placebo phase and ondansetron phase	Measurement once (at the 1 hour-mark) during each 2-hour phase
Secondary	Temperature	Difference in mean temperature between placebo phase and ondansetron phase	Hourly measurement during each 2-hour phase
Secondary	Richmond Agitation and Sedation Scale (RASS)	Difference in mean Richmond Agitation and Sedation Scale (RASS) between placebo phase and ondansetron phase. This scale goes from -5 (unraousable) to +4 (combative).	Hourly measurement during each 2-hour phase
Secondary	Critical care Pain Observation Tool (CPOT)	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).	Hourly measurement during each 2-hour phase