Continuous vs Bolus Neuromuscular Blockade Regimens in Moderate to Severe Hypoxemic Respiratory Failure and ARDS (COBRA) (COBRA)
The Effect of Continuous vs Bolus Neuromuscular Blockade Regimens for Patients With Moderate to Severe Hypoxemic Respiratory Failure and ARDS (COBRA): A Pilot Randomized Controlled Trial
Current clinical guidelines, such as those from the Surviving Sepsis Campaign and ARDSNet, recommend short-term NMBA use for patients with moderate to severe ARDS who exhibit persistent ventilator dyssynchrony or high plateau pressures despite deep sedation . However, they do not provide clear recommendations regarding the mode of administration. As a result, clinicians are left to extrapolate from limited or indirect evidence, which may lead to practice variation, uncertainty, and suboptimal care.
This pilot randomized controlled trial is designed to directly address this critical gap by comparing intermittent bolus administration versus continuous infusion of NMBAs in a pragmatic, real-world ICU setting. The study will assess feasibility metrics necessary to plan a definitive trial and generate preliminary clinical data on safety and effectiveness. By clarifying the comparative benefits and risks of each approach, the results may influence practice guidelines, reduce variation in care, and improve patient outcomes and reduce practice variation.patient outcomes, optimize resource use, and inform future guidelines on the management of moderate to severe ARDS.
Studie Overzicht
Toestand
Gedetailleerde beschrijving
Study Title: The Effect of Continuous vs Bolus Neuromuscular Blockade for Patients with Moderate to Severe HRF and ARDS: A Pilot Randomized Controlled Trial
Background:
Acute Respiratory Distress Syndrome (ARDS) affects ~10% of ICU patients and carries high morbidity and mortality. Neuromuscular blockade agents (NMBAs), especially cisatracurium, have historically been administered via continuous infusion to improve oxygenation and reduce ventilator-induced lung injury. However, recent evidence (e.g., ROSE trial) questions this approach, and emerging guidelines suggest intermittent bolus dosing may offer similar benefits with fewer adverse effects. There is a lack of direct comparative data, creating uncertainty in clinical practice.
Hypothesis & Objectives:
The study hypothesizes that a multicenter RCT comparing intermittent bolus vs continuous NMBA infusion in ARDS is feasible and that bolus dosing may show trends toward improved outcomes (e.g., ventilator-free days, fewer adverse events).
Primary objective: Assess feasibility of a definitive trial. Feasibility aims: 1. Recruitment rate (target ≥75%) 2. Protocol adherence (≥85%) 3. Data completeness (≥95%) 4. Safety monitoring of adverse events.
Secondary (exploratory) objectives: Compare 28-day ventilator-free days (VFDs), mortality, ICU/hospital length of stay, and ICU-acquired weakness.
Methods: This is a multicenter, prospective, pilot RCT in Alberta ICUs. 100 adult patients with moderate to severe ARDS will be randomized within 24 hours of diagnosis to either: 1. Intermittent bolus NMBA dosing OR 2. Continuous NMBA infusion (up to 48 hours). Both arms will receive lung-protective ventilation and guideline-based sedation.
Analysis: Feasibility outcomes will be described with 95% confidence intervals. Exploratory clinical outcomes will follow intention-to-treat principles using regression models. Results will inform design and sample size for a full-scale trial.
Risks & Mitigation: Risks such as protocol non-adherence, ICU-acquired weakness, and data loss will be managed via clinician education, adherence monitoring, and real-time data checks. Safety protocols, including allowance for rescue boluses and adherence to sedation best practices, will be enforced.
Team: Led by Drs. Parhar and Doig with a multidisciplinary team of critical care and clinical trial experts, the group has a strong track record in ICU research and implementation.
Significance & Knowledge Translation: This study addresses a critical evidence gap in ARDS care. Findings will inform future guidelines and practice by establishing whether bolus NMBA administration is a feasible, effective, and safer alternative to continuous infusion. Results will be disseminated through academic and clinical networks and will lay the groundwork for a large-scale, definitive RCT.
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
Contacten en locaties
Studiecontact
- Naam: Ken Parhar, MD MSc MPH
- Telefoonnummer: 000-000-0000
- E-mail: ken.parhar@albertahealthservices.ca
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
Inclusion Criteria:
Age ≥18 years
- Mechanically ventilated and on a controlled ventilation mode
- Diagnosis of moderate to severe ARDS (PaO₂/FiO₂ ≤150 mmHg on PEEP ≥5 cm H₂O)
- Bilateral pulmonary infiltrates consistent with ARDS
- Randomized within 24 hours of meeting ARDS criteria
Exclusion Criteria:
- Pregnancy
- Known allergy or contraindication to rocuronium
- Neuromuscular disorders (e.g., myasthenia gravis, Guillain-Barré syndrome)
- Brain death or decision for withdrawal of life-sustaining therapy
- Enrollment in a conflicting interventional trial
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Bolus Dosing
Bolus dosing
|
Intermittent administration of NMBA
Andere namen:
|
|
Actieve vergelijker: Continuous Infusion
Continuous infusion
|
Continuous infusion of NMBA
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Recruitment rate among eligible patients
Tijdsspanne: Within 48 hours of meeting ARDS criteria
|
Recruitment rate among eligible patients
|
Within 48 hours of meeting ARDS criteria
|
|
Protocol adherence rate
Tijdsspanne: for the first 28 days of mechanical ventilation
|
Protocol adherence rate
|
for the first 28 days of mechanical ventilation
|
|
Proportion of missing baseline characteristics and outcomes
Tijdsspanne: First 28 days of invasive ventilation post ARDS diagnosis.
|
Proportion of baseline characteristics and outcomes that are missing
|
First 28 days of invasive ventilation post ARDS diagnosis.
|
|
Compositive Safety
Tijdsspanne: First 28 days of invasive ventilation post ARDS diagnosis.
|
rates of ICU acquired weakness, unplanned extubation, and other SAE
|
First 28 days of invasive ventilation post ARDS diagnosis.
|
Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- REB25-1049
Plan Individuele Deelnemersgegevens (IPD)
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