Partial Neuromuscular Blockade for Lung Protective Mechanical Ventilation

NCT03646266 | Unknown Phase 4 DMC

• 1 other identifier: NL65192.029.18
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Controlled mechanical ventilation may lead to the development of diaphragm muscle atrophy, which is associated with weakness and adverse clinical outcome. Therefore, it seems reasonable to switch to partially supported ventilator modes as soon as possible. However, in patients with high respiratory drive, the application of partially supported modes may result in high lung distending pressures and diaphragm injury. Recently, the investigators published a study that demonstrated that a low dose of neuromuscular blocking agents (NMBA) facilitates lung-protective ventilation and maintains diaphragm activity in intensive care unit (ICU) patients. That study was conducted in a small (N=10), selected group of patients and partial neuromuscular blockade was applied for only 2 hours (proof-of-concept study). Therefore, further research has to be done before this strategy can be applied in clinical practice. The primary goal is to investigate the feasibility and safety of prolonged (24 hours) partial neuromuscular blockade in patients with high respiratory drive in partially supported mode. The secondary goals are to evaluate the effect of this strategy diaphragm function, lung injury, hemodynamics and systemic inflammation.

Conditions

Respiratory Insufficiency

Outcome Measures

Primary Outcomes (2)

• The percentage of breaths with tidal volume 6ml/kg predicted body weight (PBW)

  During the study period we measure at five time points of 1 hour (T0, T1, T5, T12, T24) all breaths and determine the percentage of breaths with a tidal volume of 6ml/kg PBW.

  At five time points of 1hr during the first 24hrs of the study period

• Incidence of directly related serious adverse events

  A serious adverse event is any untoward medical occurence or effect that: * results in death * is life threatening * requires prolongation of existing inpatients' hospitalization * results in persistent or significatn disability or incapacity * is a new event of the trial medication to affect the safety of the subjects, such as adverse events which are not already were described

  During the 48hrs study period

Secondary Outcomes (13)

• Number of patients completing the study without meeting the stopping criteria

  At four time points during the first 24hrs of the study period

• Effect on partial carbon dioxide (pCO2)

  During the 48hrs study period

• Effect on pH

  During the 48hrs study period

• Effect on heart rate

  During the 48hrs study period

• Effect on blood pressure

  During the 48hrs study period

Study Arms (2)

Rocuronium

EXPERIMENTAL

Titration of rocuronium bromide until tidal volume of 6ml/kg predicted body weight (PBW) is reached

Drug: Rocuronium Bromide

Control

NO INTERVENTION

Standard of care

Interventions

Rocuronium Bromide DRUG

Titration with rocuronium bromide until tidal volume 6ml/kg PBW

Also known as: Esmeron

Rocuronium

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• high respiratory drive, defined as tidal volume \> 8ml/kg PBW on inspiratory support of 12 cmH2O.
• sedation level: richmond agitation-sedation scale (RASS) ≤ -3
• ventilated in pressure support mode

You may not qualify if:

• recent use of NMBA (\< 2 hrs)
• arterial pH \< 7.25
• hemodynamic instability, i.e. high dose vasopressors (\>0.5 μg/kg/min) or inotropes (dobutamine \>15 μg/kg/min or enoximone \>25 μg/kg/min)
• intracranial pressure \> 20 cmH2O
• past medical history of neuromuscular disorders
• known pregnancy
• known previous anaphylactic reaction to NMBA's.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VUmc

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Rocuronium

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Diana Jansen, Drs.

CONTACT

+31(0)613225643; diana.jansen@radboudumc.nl

L.M.A. Heunks, prof.dr.

CONTACT

l.heunks@vumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Collaborating investigator

Model Details: pilot randomized controlled trial (RCT)

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: August 24, 2018
• Study Start: August 15, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: May 20, 2020

Record last verified: 2020-05

Locations

NL (1)