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

Primary Purpose

Acute Respiratory Distress Syndrome

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Placebo
Ondansetron
Sponsored by
Hopital du Sacre-Coeur de Montreal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring ARDS, Ondansetron

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Sacré-Coeur de MontréalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Ondansetron

Arm Description

All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.

All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Respiratory rate
Difference in mean respiratory rate between placebo phase and ondansetron phase
Tidal volume
Difference in mean tidal volume between placebo phase and ondansetron phase
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
Esophageal pressure swings
Difference in mean esophageal pressure swings between placebo phase and ondansetron phase
Transpulmonary pressure swings
Difference in mean transpulmonary pressure swings between placebo phase and ondansetron phase
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
Peak electrical activity of the diaphragm (Eadi)
Difference in mean peak Eadi between placebo phase and ondansetron phase
Area under the Eadi curve
Difference in area under the Eadi curve between placebo phase and ondansetron phase
End-tidal CO2 (EtCO2)
Difference in mean EtCO2 between placebo phase and ondansetron phase
Volume of expired CO2 (VCO2)
Difference in mean VCO2 between placebo phase and ondansetron phase
Oxygen saturation estimated by pulse oximetry (SpO2)
Difference in mean SpO2 between placebo phase and ondansetron phase
Partial pressure of carbon dioxide in arterial blood (PaCO2)
Difference in mean PaCO2 between placebo phase and ondansetron phase
Partial pressure of oxygen in arterial blood (PaO2)
Difference in mean PaO2 between placebo phase and ondansetron phase
Heart rate
Difference in mean heart rate between placebo phase and ondansetron phase
Mean arterial pressure (MAP)
Difference in mean MAP between placebo phase and ondansetron phase
Corrected QT length (QTc)
Difference in QTc between placebo phase and ondansetron phase
Temperature
Difference in mean temperature between placebo phase and ondansetron phase
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).
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).

Full Information

First Posted
August 17, 2022
Last Updated
September 26, 2023
Sponsor
Hopital du Sacre-Coeur de Montreal
Collaborators
Fonds de la Recherche en Santé du Québec
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1. Study Identification

Unique Protocol Identification Number
NCT05514483
Brief Title
5-HT3 Receptor Antagonist and Respiratory Drive in Patients With ARDS
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2022 (Actual)
Primary Completion Date
March 6, 2024 (Anticipated)
Study Completion Date
May 6, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hopital du Sacre-Coeur de Montreal
Collaborators
Fonds de la Recherche en Santé du Québec

4. Oversight

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
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
ARDS, Ondansetron

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Non-randomized crossover 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.
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.
Arm Title
Ondansetron
Arm Type
Active Comparator
Arm Description
All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
NaCl 0.9%, Normal Saline, Sodium chloride
Intervention Description
Single intravenous dose of 10 mL of sodium chloride (NaCl) 0.9% over 15 minutes.
Intervention Type
Drug
Intervention Name(s)
Ondansetron
Other Intervention Name(s)
Ondansetron hydrochloride dihydrate
Intervention Description
Single intravenous dose of ondansetron hydrochloride dihydrate 0.15 mg/kg (maximum 16 mg) in 10 mL of NaCl 0.9% over 15 minutes.
Primary Outcome Measure Information:
Title
Pressure-time product of the esophageal pressure per minute
Description
Difference in mean pressure-time product of the esophageal pressure per minute between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Secondary Outcome Measure Information:
Title
Respiratory rate
Description
Difference in mean respiratory rate between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Tidal volume
Description
Difference in mean tidal volume between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Pressure-time product of the esophageal pressure per breath
Description
Difference in mean pressure-time product of the esophageal pressure per breath between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Esophageal pressure swings
Description
Difference in mean esophageal pressure swings between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Transpulmonary pressure swings
Description
Difference in mean transpulmonary pressure swings between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Estimated occlusion pressure at 0.1 msec (P0.1)
Description
Difference in mean estimated occlusion pressure at 0.1 msec (P0.1) between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Peak electrical activity of the diaphragm (Eadi)
Description
Difference in mean peak Eadi between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Area under the Eadi curve
Description
Difference in area under the Eadi curve between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
End-tidal CO2 (EtCO2)
Description
Difference in mean EtCO2 between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Volume of expired CO2 (VCO2)
Description
Difference in mean VCO2 between placebo phase and ondansetron phase
Time Frame
Continuous measurement during each 2-hour phase
Title
Oxygen saturation estimated by pulse oximetry (SpO2)
Description
Difference in mean SpO2 between placebo phase and ondansetron phase
Time Frame
Measurement every 5 minutes during each 2-hour phase
Title
Partial pressure of carbon dioxide in arterial blood (PaCO2)
Description
Difference in mean PaCO2 between placebo phase and ondansetron phase
Time Frame
Measurement every 30 minutes during each 2-hour phase
Title
Partial pressure of oxygen in arterial blood (PaO2)
Description
Difference in mean PaO2 between placebo phase and ondansetron phase
Time Frame
Measurement every 30 minutes during each 2-hour phase
Title
Heart rate
Description
Difference in mean heart rate between placebo phase and ondansetron phase
Time Frame
Measurement every 5 minutes during each 2-hour phase
Title
Mean arterial pressure (MAP)
Description
Difference in mean MAP between placebo phase and ondansetron phase
Time Frame
Measurement every 5 minutes during each 2-hour phase
Title
Corrected QT length (QTc)
Description
Difference in QTc between placebo phase and ondansetron phase
Time Frame
Measurement once (at the 1 hour-mark) during each 2-hour phase
Title
Temperature
Description
Difference in mean temperature between placebo phase and ondansetron phase
Time Frame
Hourly measurement during each 2-hour phase
Title
Richmond Agitation and Sedation Scale (RASS)
Description
Difference in mean Richmond Agitation and Sedation Scale (RASS) between placebo phase and ondansetron phase. This scale goes from -5 (unraousable) to +4 (combative).
Time Frame
Hourly measurement during each 2-hour phase
Title
Critical care Pain Observation Tool (CPOT)
Description
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).
Time Frame
Hourly measurement during each 2-hour phase
Other Pre-specified Outcome Measures:
Title
Enrolment
Description
Number of eligible patients and enrolled patients.
Time Frame
Monthly through study completion (estimated 6 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Virginie Williams
Phone
514-338-2222
Ext
583327
Email
virginie.williams.cnmtl@ssss.gouv.qc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yiorgos Alexandros Cavayas, MD MSc FRCPC
Organizational 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
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Sacré-Coeur de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4J1C5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Virginie Williams, PhD
Phone
514-338-2222
Ext
583327
Email
virginie.williams.cnmtl@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Yiorgos Alexandros Cavayas, MD MSc FRCPC
First Name & Middle Initial & Last Name & Degree
David Williamson, BPharm PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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