このページは自動翻訳されたものであり、翻訳の正確性は保証されていません。を参照してください。 英語版 ソーステキスト用。

Ondansetron for the Prevention of Patient Self-Inflicted Lung Injury in Patients With ARDS - Pilot RCT (OSIRIS-1)

2026年5月8日 更新者：Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

A Pilot, Randomized, Controlled Clinical Trial Evaluating Ondansetron for the Prevention of Patient Self-Inflicted Lung Injury Through Inhibition of Respiratory Drive in Patients With Acute Respiratory Distress Syndrome (OSIRIS-1)

Acute Respiratory Distress Syndrome (ARDS) is a serious condition where the lungs become inflamed, leading to severe breathing difficulties. Despite advances in medical care, ARDS remains a life-threatening illness with a high risk of death and long-term complications. One way doctors help ARDS patients is by using special ventilation techniques to protect the lungs from further damage. However, this often requires heavy sedation or even paralyzing medications, which can lead to other problems like delirium, muscle weakness, and longer hospital stays. Allowing patients to breathe on their own might offer benefits, but it also comes with risks. Many ARDS patients have a very strong urge to breathe, which can cause them to overexert their lungs, potentially leading to additional lung damage, known as patient selfinflicted lung injury (P-SILI). Our early research suggests that a medication called ondansetron, commonly used to prevent nausea, might help reduce this strong breathing drive in ARDS patients, possibly preventing further lung injury. The OSIRIS research program is designed to explore whether ondansetron can protect ARDS patients from P-SILI, ultimately improving their chances of survival and reducing long-term complications. The first part of this program, OSIRIS-1, is a small pilot study where we will test the feasibility of running a larger, more definitive trial. We will randomly assign ARDS patients to receive either ondansetron or a placebo, given intravenously four times a day, and monitor their heart rhythms closely to ensure safety. We will also track how well patients stick to the study plan and whether ondansetron helps reduce their breathing drive and lung strain. If successful, this research could lead to new ways of treating ARDS that rely less on heavy sedation, potentially improving outcomes for these critically ill patients and setting the stage for larger, more comprehensive studies in the future.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening inflammatory lung condition with high mortality and long-term morbidity. Lung-protective ventilation - targeting low tidal volumes and driving pressures - is one of the few proven interventions but often requires deep sedation and neuromuscular blockade (NMB), which are associated with delirium, ICU-acquired weakness, and prolonged ICU stays. Maintaining spontaneous breathing can offer physiological advantages but is frequently limited by excessive respiratory drive, which increases the risk of patient self-inflicted lung injury (P-SILI). Lung inflammation leading to stimulation and sensitization of pulmonary vagal afferent Cfibers could contribute to excessive respiratory effort. Stimulation of pulmonary C-fibers by serotonin increases respiratory rate in animal models through 5-HT receptors. Our previous data suggest that 3 ondansetron, a 5-HT receptor antagonist, attenuates respiratory drive and effort. We hypothesize that 3 this effect may reduce the need for sedation and paralysis, minimize P-SILI, and ultimately improve outcomes in ARDS.

OBJECTIVES: The overarching goal of the OSIRIS research program is to evaluate whether regular intravenous ondansetron can improve patient-important outcomes (survival, ventilator-free days and long term neurocognitive function) in patients with ARDS. With the OSIRIS-1 pilot study, our objective is to assess:

Feasibility:

[RQ1] What is the adherence to the study protocol? [PRIMARY] [RQ2] What is the completeness of the data collection? [RQ3] What is the recruitment rate?

Preliminary mechanistic efficacy and safety:

[RQ4] Does it decrease respiratory effort? [RQ5] Does it reduce exposure to sedatives, opioids and neuromuscular blockers? [RQ6] Is the intervention safe?

METHODS: OSIRIS-1 is a multicenter, double-blind, parallel-group, phase 2 and feasibility pilot RCT. We will enroll 76 invasively mechanically ventilated adults with moderate-to-severe ARDS (PaO :FiO2 < 200). Participants will be randomized to receive ondansetron 8 mg IV or placebo every 8 hours until liberation from invasive mechanical ventilation. Feasibility will be assessed through protocol adherence (defined as scheduled doses administered within ±2 hours), completeness of key clinical outcomes (ventilator-free days, coma/delirium-free days, 90-day survival), and site-level recruitment metrics. For preliminary efficacy, we will estimate respiratory drive using Pmus (derived from occlusion pressure, ΔPocc), measured three times daily by respiratory therapists. We will also measure P0.1, respiratory rate, and other ventilatory parameters. For safety, we will monitor the occurrence of ventricular arrhythmias, serotonin syndrome, and other serious adverse events.

IMPACT: OSIRIS-1 will provide essential data on mechanistic efficacy, safety, and feasibility to inform the design of a future large-scale trial evaluating patient-important outcomes. By targeting respiratory drive pharmacologically, we may enable safer spontaneous breathing, reduce the harms of oversedation and paralysis, and ultimately improve outcomes in ARDS.

研究の種類

介入

入学 (推定)

76

段階

  • フェーズ2
  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

  • カナダ
    • Quebec
      • Montreal、Quebec、カナダ、H4J 1C5
        • Hôpital du Sacré-Cœur de Montréal
        • コンタクト：
        • 主任研究者：
          • Yiorgos Alexandros Cavayas, MD MSc

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  • Moderate-to-severe ARDS with all of the following:
  • Hypoxemic respiratory failure with PaO2:FiO2 < 200 (on IMV with PEEP ≥ 5)
  • Precipitated within 1 week of an acute condition
  • Bilateral opacities on chest radiography and computed tomography or bilateral B lines and/or consolidations on ultrasound not fully explained by effusions, atelectasis, or nodules/masses
  • Pulmonary edema not exclusively or primarily attributable to cardiogenic pulmonary edema/fluid overload
  • Hypoxemia/gas exchange abnormalities not primarily attributable to atelectasis
  • IMV initiated < 96 hours
  • Extubation not anticipated within 24 hours

Exclusion Criteria:

  • Neuromuscular disease impairing spontaneous breathing
  • Pregnancy
  • Liver cirrhosis (Child B or C) or other severe impairment of hepatic function
  • Bradycardia (baseline pulse<50/min) on screening day
  • Known long QT syndrome
  • History of sustained ventricular tachycardia
  • Active digestive / abdominal infection44
  • QTc prolongation > 470 msec in men and > 480 msec in women on screening day
  • On a medication at high risk of QT prolongation (Table 5)50
  • On two or more serotonergic medications (Table 6)51
  • Hypersensitivity / intolerance to 5-HT3 antagonists
  • Patient deemed unlikely to survive past 24 hours or being transitioned to a fully palliative philosophy of care

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：Ondansetron
The first dose of intravenous ondansetron will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.
薬：Ondansetron hydrochloride 8 mg IV Q8H
Participants randomized to the ondansetron arm will receive ondansetron hydrochloride dihydrate 8 mg IV every 8 hours, administered in 10 mL of 0.9% sodium chloride in prepared syringes over 15 minutes.
プラセボコンパレーター：Placebo
The first dose of intravenous placebo will be administered within 24 hours of randomization, every 8 hours, for duration of invasive mechanical ventilation.
薬：0.9 % Normal Saline 10 ml
Participants randomized to the placebo arm will receive 10 mL of 0.9% sodium chloride in prepared syringes administered over 15 minutes every 8 hours, matching the appearance, volume, and administration modalities of ondansetron to maintain blinding.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
protocol adherence
時間枠：duration of intervention (duration of invasive mechanical ventilation)
Adherence will be measured as the proportion of scheduled doses (±2h window) administered; protocol-defined withholdings (e.g., electrophysiological disturbances) will be documented but not counted as non-adherence.
duration of intervention (duration of invasive mechanical ventilation)

二次結果の測定

結果測定
メジャーの説明
時間枠
Outcome data completeness
時間枠：90 days
Data completeness for 90 day survival, 28 day ventilator-free days, and 14 day coma-and-delirium-free days.
90 days
Enrolment rate
時間枠：Duration of the study
Patients enrolled by site by 12-month period
Duration of the study

その他の成果指標

結果測定
メジャーの説明
時間枠
Pmus
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
Pmus will be estimated by the occlusion pressure maneuvre, measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
P0.1
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
P0.1 will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
Respiratory Rate
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
Respiratory Rate will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
Tidal volume
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
Tidal volume will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
PaO2:FiO2 ratio
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
PaO2:FiO2 ratio will be measured 3 times per day.
duration of the intervention (duration of invasive mechanical ventilation)
Number of days of deep sedation
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
A deep sedation will be defined as a day in which a Richmond Agitation and Sedation Scale (RASS) of -4 or -5 was present for the majority of the day
duration of the intervention (duration of invasive mechanical ventilation)
Average daily oral morphine equivalent
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
All opiates received during a given day will be converted in oral morphine equivalent and summed up.
duration of the intervention (duration of invasive mechanical ventilation)
Days with NMB administration
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
Defined by having received any dose or neuromuscular blocker during a given day.
duration of the intervention (duration of invasive mechanical ventilation)
Sustained Ventricular Arrhythmia
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
Defined as ventricular tachycardia or fibrillation sustained for ≥30 seconds or requiring termination due to hemodynamic compromise in <30 seconds.
duration of the intervention (duration of invasive mechanical ventilation)
Serotonin Syndrome
時間枠：duration of the intervention (duration of invasive mechanical ventilation)
Serotonin syndrome (ie, serotonin toxicity) is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities.
duration of the intervention (duration of invasive mechanical ventilation)
90-day survival
時間枠：90 days
Being alive at 90 days
90 days
Ventilator-Free Days
時間枠：28 days
Number of days alive and free of mechanical ventilation in the first 28 days with death before day 28 counted as 0
28 days
Coma-and-delirium-free days
時間枠：14 days
Number of days alive without delirium nor coma from any cause in the first 14 days
14 days

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

捜査官

  • 主任研究者：Yiorgos Alexandros Cavayas, MD MSc、Centre Intégré Universitaire de Santé et Services Sociaux du Nord-de-l'Ile-de-Montréal - Hôpital du Sacré-Coeur de Montréal
  • 主任研究者：David Williamson, BPharm, PhD、Centre Intégré Universitaire de Santé et Services Sociaux du Nord-de-l'Ile-de-Montréal - Hôpital du Sacré-Coeur de Montréal

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年10月1日

一次修了 (推定)

2028年10月1日

研究の完了 (推定)

2029年10月1日

試験登録日

最初に提出

2026年5月8日

QC基準を満たした最初の提出物

2026年5月8日

最初の投稿 (実際)

2026年5月14日

学習記録の更新

投稿された最後の更新 (実際)

2026年5月14日

QC基準を満たした最後の更新が送信されました

2026年5月8日

最終確認日

2026年5月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • MP-32-2026-3061

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

未定

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

購読する