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Partial Neuromuscular Blockade for Lung Protective Mechanical Ventilation

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ClinicalTrials.gov Identifier: NCT03646266
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
Diana Jansen, VU University Medical Center

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.


Condition or disease Intervention/treatment Phase
Respiratory Insufficiency Drug: Rocuronium Bromide Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: pilot randomized controlled trial (RCT)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Partial Neuromuscular Blockade to Facilitate Lung and Diaphragm Protective Mechanical Ventilation in Intensive Care Unit Patients: a Randomized Controlled Pilot Study
Actual Study Start Date : August 15, 2018
Estimated Primary Completion Date : March 30, 2019
Estimated Study Completion Date : March 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Rocuronium
Titration of rocuronium bromide until tidal volume of 6ml/kg predicted body weight (PBW) is reached
Drug: Rocuronium Bromide
Titration with rocuronium bromide until tidal volume 6ml/kg PBW
Other Name: Esmeron

No Intervention: Control
Standard of care



Primary Outcome Measures :
  1. The percentage of breaths with tidal volume 6ml/kg predicted body weight (PBW) [ Time Frame: At five time points of 1hr during the first 24hrs of the study period ]
    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.

  2. Incidence of directly related serious adverse events [ Time Frame: During the 48hrs study period ]

    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


Secondary Outcome Measures :
  1. Number of patients completing the study without meeting the stopping criteria [ Time Frame: At four time points during the first 24hrs of the study period ]

    After each time point (T0, T1, T5 and T12) we screen if the patient meets one of the stopping criteria, defined as:

    • potential of hydrogen (pH) < 7.20
    • heart rate > 100 beats per minute or an increase of > 20% from baseline for more than 20 minutes
    • increase in mean arterial blood pressure of > 20% for more than 20 minutes

  2. Effect on partial carbon dioxide (pCO2) [ Time Frame: During the 48hrs study period ]

    At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on pCO2 (in kPa), in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups

  3. Effect on pH [ Time Frame: During the 48hrs study period ]

    At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on pH, in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  4. Effect on heart rate [ Time Frame: During the 48hrs study period ]

    During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the heart rate (in beats per minute), in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  5. Effect on blood pressure [ Time Frame: During the 48hrs study period ]

    During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the blood pressure (millimetre(s) of mercury (mmHg)), in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  6. Effect on respiratory rate [ Time Frame: During the 48hrs study period ]

    During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the respiratory rate (in breaths per minute) in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  7. Effect on peripheral capillary oxygen saturation (SpO2) [ Time Frame: During the 48hrs study period ]

    During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the SpO2 (%) in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  8. Effect on partial oxygen pressure (pO2) [ Time Frame: During the 48hrs study period ]

    At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on pO2 (in kPa), in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  9. Effect on work of breathing (WOB) [ Time Frame: During the first 24hrs of the study period ]

    During the study period we will collect at five time points (T0, T1, T5, T12 and T24) the WOB (in Joule) in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  10. Effect on pressure time product (PTP) [ Time Frame: During the first 24hrs of the study period ]

    During the study period we will collect at five time points (T0, T1, T5, T12 and T24) the PTP (in cmH2O per second) in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  11. Effect on tumor necrosis factor (TNF)-alfa [ Time Frame: During the first 24hrs of the study period ]

    At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on TNF-alfa concentration (in pg/ml), in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  12. Effect on interleukin(IL)-6 and IL-8 [ Time Frame: During the first 24hrs of the study period ]

    At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on IL-6 and IL-8 concentration (in pg/ml), in order to:

    • determine if there were differences between the start and end of the study period
    • investigate if there were differences between both study groups.

  13. Amount of days on mechanical ventilation [ Time Frame: Until 30 days after the end of the study period ]
    After 30 days we will investigate if there were differences between both groups in the duration of mechanical ventilation.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03646266


Contacts
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Contact: Diana Jansen, Drs. +31(0)613225643 diana.jansen@radboudumc.nl
Contact: L.M.A. Heunks, prof.dr. l.heunks@vumc.nl

Locations
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Netherlands
VUmc Recruiting
Amsterdam, Netherlands
Contact: L.M.A. Heunks, Prof.dr.         
Sponsors and Collaborators
VU University Medical Center

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Responsible Party: Diana Jansen, Collaborating investigator, VU University Medical Center
ClinicalTrials.gov Identifier: NCT03646266     History of Changes
Other Study ID Numbers: NL65192.029.18
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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

Additional relevant MeSH terms:
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Respiratory Insufficiency
Pulmonary Valve Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Rocuronium
Bromides
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants