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

Montreal Sacred Heart Hospital

Status and phase: Enrolling; Phase 4

Conditions: Acute Respiratory Distress Syndrome

Treatments: Drug: Placebo; Drug: Ondansetron

Study type: Interventional

Funder types: Other

Identifiers

NCT05514483

2023-2502

Details and patient eligibility

About

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.

Enrollment: 10 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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10 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Ondansetron

Active Comparator group

Description:

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

Treatment:

Drug: Ondansetron