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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Pressure-time product of the esophageal pressure per minute
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.
干预措施: Placebo (Drug)
Ondansetron
All participants will receive a single injection of placebo, followed, three hours later, by a single injection of ondansetron.
干预措施: Ondansetron (Drug)
结局指标
主要结局
Pressure-time product of the esophageal pressure per minute
时间窗: 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
次要结局
- Temperature(Hourly measurement during each 2-hour phase)
- Respiratory rate(Continuous measurement during each 2-hour phase)
- Area under the Eadi curve(Continuous measurement during each 2-hour phase)
- Volume of expired CO2 (VCO2)(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)
- Estimated occlusion pressure at 0.1 msec (P0.1)(Continuous measurement during each 2-hour phase)
- End-tidal CO2 (EtCO2)(Continuous measurement during each 2-hour phase)
- Corrected QT length (QTc)(Measurement once (at the 1 hour-mark) during each 2-hour phase)
- Peak electrical activity of the diaphragm (Eadi)(Continuous measurement during each 2-hour phase)
- Oxygen saturation estimated by pulse oximetry (SpO2)(Measurement every 5 minutes during each 2-hour phase)
- Partial pressure of carbon dioxide in arterial blood (PaCO2)(Measurement every 30 minutes during each 2-hour phase)
- Partial pressure of oxygen in arterial blood (PaO2)(Measurement every 30 minutes during each 2-hour phase)
- Heart rate(Measurement every 5 minutes during each 2-hour phase)
- Mean arterial pressure (MAP)(Measurement every 5 minutes during each 2-hour phase)
- Richmond Agitation and Sedation Scale (RASS)(Hourly measurement during each 2-hour phase)
- Critical care Pain Observation Tool (CPOT)(Hourly measurement during each 2-hour phase)
研究者
Yiorgos Alexandros Cavayas
Principal Investigator
Hopital du Sacre-Coeur de Montreal