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

NCT05514483 | Unknown Phase 4

• 1 other identifier: 2023-2502
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

ARDS; Ondansetron

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

• Respiratory rate

  Continuous measurement during each 2-hour phase

• Tidal volume

  Continuous measurement during each 2-hour phase

• Pressure-time product of the esophageal pressure per breath

  Continuous measurement during each 2-hour phase

• Esophageal pressure swings

  Continuous measurement during each 2-hour phase

• Transpulmonary pressure swings

  Continuous measurement during each 2-hour phase

Other Outcomes (1)

• Enrolment

  Monthly through study completion (estimated 6 months)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Ondansetron

ACTIVE COMPARATOR

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

Drug: Ondansetron

Interventions

Placebo DRUG

Single intravenous dose of 10 mL of sodium chloride (NaCl) 0.9% over 15 minutes.

Also known as: NaCl 0.9%, Normal Saline, Sodium chloride

Placebo

Ondansetron DRUG

Single intravenous dose of ondansetron hydrochloride dihydrate 0.15 mg/kg (maximum 16 mg) in 10 mL of NaCl 0.9% over 15 minutes.

Also known as: Ondansetron hydrochloride dihydrate

Ondansetron

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal: lead
• Fonds de la Recherche en Santé du Québec: collaborator

Study Sites (1)

Hôpital Sacré-Coeur de Montréal

Montreal, Quebec, H4J1C5, Canada

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Sodium Chloride; Saline Solution; Ondansetron

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virginie Williams

CONTACT

514-338-2222; virginie.williams.cnmtl@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Non-randomized crossover controlled trial with two interventions and one sequence. The sequence of treatment is first placebo and secondly ondansetron.

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 24, 2022
• Study Start: November 10, 2022
• Primary Completion: March 6, 2024
• Study Completion: May 6, 2024
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)