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

• Sponsor: Hopital du Sacre-Coeur de Montreal (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05514483
• Collaborator: Fonds de la Recherche en Santé du Québec (Other)
• Enrollment: 10
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 8
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome	Drug: Placebo; Drug: Ondansetron Injection	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Crossover Assignment
• Intervention Model Description: Non-randomized crossover single-blind controlled trial with two interventions and one sequence. The sequence of treatment is first placebo and secondly ondansetron.Non-randomized crossover single-blind controlled trial with two interventions and one sequence. The sequence of treatment is first placebo and secondly ondansetron.
• Masking: None (Open Label)
• 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.
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Sep 6, 2022
• Anticipated Primary Completion Date: Mar 6, 2023
• Anticipated Study Completion Date: May 6, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Non-randomized, single sequence of Placebo injection followed by Ondansetron Injection All participants will receive a single injection of placebo, followed, two hours later, by a single injection of ondansetron.	Drug: Placebo; Single intravenous dose of 10 mL of sodium chloride (NaCl) 0.9% over 15 minutes.; Other Names: NaCl 0.9% Normal Saline Sodium chloride ; Drug: Ondansetron Injection; Single intravenous dose of ondansetron hydrochloride dihydrate 0.15 mg/kg (maximum 16 mg) in 10 mL of NaCl 0.9% over 15 minutes.; Other Names: Ondansetron hydrochloride dihydrate Ondansetron hydrochloride Ondansetron

Outcome Measures

Primary Outcome Measures

1. 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

1. Respiratory rate [Continuous measurement during each 2-hour phase]

   Difference in mean respiratory rate between placebo phase and ondansetron phase

2. Tidal volume [Continuous measurement during each 2-hour phase]

   Difference in mean tidal volume between placebo phase and ondansetron phase

3. 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

4. Esophageal pressure swings [Continuous measurement during each 2-hour phase]

   Difference in mean esophageal pressure swings between placebo phase and ondansetron phase

5. Transpulmonary pressure swings [Continuous measurement during each 2-hour phase]

   Difference in mean transpulmonary pressure swings between placebo phase and ondansetron phase

6. 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

7. 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

8. 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

9. End-tidal CO2 (EtCO2) [Continuous measurement during each 2-hour phase]

   Difference in mean EtCO2 between placebo phase and ondansetron phase

10. Volume of expired CO2 (VCO2) [Continuous measurement during each 2-hour phase]

    Difference in mean VCO2 between placebo phase and ondansetron phase

11. 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

12. 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

13. 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

14. Heart rate [Measurement every 5 minutes during each 2-hour phase]

    Difference in mean heart rate between placebo phase and ondansetron phase

15. Mean arterial pressure (MAP) [Measurement every 5 minutes during each 2-hour phase]

    Difference in mean MAP between placebo phase and ondansetron phase

16. 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

17. Temperature [Hourly measurement during each 2-hour phase]

    Difference in mean temperature between placebo phase and ondansetron phase

18. 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).

19. 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).

Other Outcome Measures

1. Enrolment [Monthly through study completion (estimated 6 months)]

   Number of eligible patients and enrolled patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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 alveolar infiltrates on chest X-ray not present for more than 7 days

• 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) >

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Sacré-Coeur de Montréal	Montréal	Quebec	Canada	H9C3A7

Sponsors and Collaborators

• Hopital du Sacre-Coeur de Montreal
• Fonds de la Recherche en Santé du Québec

Investigators

• Principal Investigator: Yiorgos Alexandros Cavayas, MD MSc FRCPC, 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yiorgos Alexandros Cavayas, Principal Investigator, Hopital du Sacre-Coeur de Montreal
• ClinicalTrials.gov Identifier: NCT05514483
• Other Study ID Numbers: 2023-2502
• First Posted: Aug 24, 2022
• Last Update Posted: Aug 24, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Yiorgos Alexandros Cavayas, Principal Investigator, Hopital du Sacre-Coeur de Montreal: ARDS; Ondansetron
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Ondansetron

Study Results

No Results Posted as of Aug 24, 2022