Partial Neuromuscular Blockade in Acute Hypoxemic Respiratory Failure (PNEUMA)

PNEUMA is a preliminary safety and feasibility trial of a novel approach to the titration of neuromuscular blockade (NMB) to safe spontaneous breathing in patients with moderate to severe acute hypoxemic respiratory failure (AHRF) supported with invasive mechanical ventilation.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Insufficiency; Neuromuscular Blockade; Mechanical Ventilation
• Intervention / Treatment: Drug: Cisatracurium

Detailed Description

Controlling respiratory effort in patients with AHRF can be challenging, as they often exhibit a very high respiratory drive despite receiving high doses of sedatives. Consequently, these patients usually receive full neuromuscular blockade, with the goal to avoid such injurious respiratory efforts. Unfortunately, full neuromuscular blockade is not without complications. To address this issue, the use of partial neuromuscular blockade has been proposed as a strategy to maintain respiratory muscle activity while providing lung protective ventilation.

The objective of this study is to demonstrate the safety and feasibility of safe spontaneous breathing using partial NMB in moderato to severe AHRF patients supported with invasive mechanical ventilation.

Once adequate sedation has been ensured, an infusion of cisatracurium will be started to maintain spontaneous breathing with moderate levels of inspiratory effort, defined by expiratory occlusion pressure (Pocc) between -5 and -15 cmH2O. After establishing a sedation and NMB dosing regimen at which safe spontaneous breathing is achieved, we will document whether these targets can be maintained over a 48-hour period.

On December 11 2025, this study has been amended to broaden eligibility criteria from patients with acute respiratory distress syndrome supported on extracorporeal membrane oxygenation (ECMO) to patients with AHRF supported with invasive mechanical ventilation or with venovenous-ECMO. Additionally, the study intervention duration was extended from 24 hours to 48 hours or until hypoxemia is resolved (FiO2 ≤ 40% on PEEP ≤ 8 cmH2O), whichever occurs first. Finally, the study intervention was modified to remove the use of esophageal balloon, and to include sedation and neuromuscular blockade titration targeting Pocc between -5 to -15 cmH2O and according to predefined safety criteria assessed using train of four, respiratory drive and comfort assessments. A total of 15 patients will be enrolled after the amendment, in addition to the 8 patients already enrolled, for a total of 23 patients. Going forward, only patients in whom the intervention is initiated will count toward the study sample size.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Glauco M. Plens, MD, PhD; Phone Number: 4373299590; Email: glauco.plens@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Recruiting
      • University Health Network
      • Contact: Glauco Plens, MD PhD; Email: glauco.plens@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients supported on invasive mechanical ventilation for moderate to severe AHRF (PaO2/FiO2 < 150 mm Hg or FiO2 ≥ 60% with an SpO2 ≤ 97% or receiving venovenous extracorporeal membrane oxygenation)

Exclusion Criteria:

1. Contraindication to neuromuscular blockade (allergy, history of malignant hyperthermia)
2. Contraindication to ulnar nerve stimulation (bilateral peripheral neuropathy, skin burns on both wrists)
3. Previous history of a formally diagnosed neuromuscular disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Partial NMB

Drug: Cisatracurium; Cisatracurium will be infused to achieve Pocc targets after ensuring adequate sedation. Sedation will be titrated to avoid dyspnea, assessed with P0.1 targets between -1.5 and -3.5 cmH2O and Mechanical Ventilation Respiratory-Distress Observation Scale (MV-RDOS) ≤ 3. If there is no sign of dyspnea or discomfort based on P0.1, MV-RDOS, hemodynamics and the train-of-four ratio is ≥ 60% (compatible with ability to interact using peripheral muscles), sedation will be carefully reduced. After establishing a sedation and NMB strategy at which safe spontaneous breathing is achieved, we will seek to determine whether these targets can be maintained over a 48-hour period or until hypoxemia is resolved (FiO2 ≤ 40% on PEEP ≤ 8 cmH2O), whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of patients achieving and maintaining targeted expiratory occlusion pressure (Pocc)	Assessed for 48 hours after study intervention initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of serious adverse events		Assessed for 48 hours after study intervention initiation
Paralysis Recall	Evaluted using the modified Brice questionnaire.	Assessed after 48 hours of the study intervention, as soon as the patient is extubated and oriented.

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Ewan Goligher, MD, PhD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 24, 2020

Study Record Updates

• Last Update Posted (Estimated): January 6, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; cisatracurium
• Other Study ID Numbers: 19-5975

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No