Respiratory InsufficiencyPhase 4NCT03646266
Partial Neuromuscular Blockade for Lung Protective Mechanical Ventilation
A Phase 4 study testing Rocuronium Bromide in people with Respiratory Insufficiency, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Insufficiency
- What is being tested?
- Rocuronium Bromide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Aug 2018to 31 Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
L.M.A. Heunks, prof.dr. contact
Netherlands1 site, 1 recruiting
- Recruiting
VUmc
Amsterdam
L.M.A. Heunks, Prof.dr.
About this study
Official title: Partial Neuromuscular Blockade to Facilitate Lung and Diaphragm Protective Mechanical Ventilation in Intensive Care Unit Patients: a Randomized Controlled Pilot Study
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
- Being tested
- Rocuronium Bromide
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rocuronium BromideDrug
Also called Esmeron
Titration with rocuronium bromide until tidal volume 6ml/kg PBW
| Study group | Role | What they receive |
|---|---|---|
| Rocuronium | Experimental | Titration of rocuronium bromide until tidal volume of 6ml/kg predicted body weight (PBW) is reached Receives: Drug: Rocuronium Bromide |
| Control | No intervention | Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: During the 48hrs study period
Secondary outcomes (13)
Number of patients completing the study without meeting the stopping criteria
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
Measured: At four time points during the first 24hrs of the study period
Effect on partial carbon dioxide (pCO2)
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
Measured: During the 48hrs study period
Effect on pH
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.
Measured: During the 48hrs study period
Effect on heart rate
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.
Measured: During the 48hrs study period
Effect on blood pressure
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.
Measured: During the 48hrs study period
Effect on respiratory rate
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.
Measured: During the 48hrs study period
Effect on peripheral capillary oxygen saturation (SpO2)
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.
Measured: During the 48hrs study period
Effect on partial oxygen pressure (pO2)
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.
Measured: During the 48hrs study period
Effect on work of breathing (WOB)
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.
Measured: During the first 24hrs of the study period
Effect on pressure time product (PTP)
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.
Measured: During the first 24hrs of the study period
Effect on tumor necrosis factor (TNF)-alfa
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.
Measured: During the first 24hrs of the study period
Effect on interleukin(IL)-6 and IL-8
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.
Measured: During the first 24hrs of the study period
Amount of days on mechanical ventilation
After 30 days we will investigate if there were differences between both groups in the duration of mechanical ventilation.
Measured: Until 30 days after the end of the study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start15 Aug 2018
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory InsufficiencyStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- pilot randomized controlled trial (RCT)
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Diana Jansen, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646266
- Sponsor's protocol ID
- NL65192.029.18
- Status last verified
- May 2020
- First submitted
- 26 Jul 2018
- Last updated
- 20 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Partial Neuromuscular Blockade to Facilitate Lung and Diaphragm Protective Mechanical Ventilation in Intensive Care Unit Patients: a Randomized Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT03646266
- Acronym / sponsor ID
- NL65192.029.18
- Conditions
- Respiratory Insufficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 15 Aug 2018 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 24 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- pilot randomized controlled trial (RCT)
| Arm | Type | Receives |
|---|---|---|
| Rocuronium | Experimental | Drug: Rocuronium BromideTitration of rocuronium bromide until tidal volume of 6ml/kg predicted body weight (PBW) is reached |
| Control | No intervention | –Standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rocuronium BromideAlso: EsmeronTitration with rocuronium bromide until tidal volume 6ml/kg PBW | Drug | Rocuronium |
Primary outcome
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.
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
13 secondary outcomes
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
Effect on partial carbon dioxide (pCO2)
Time frame: During the 48hrs study period
Effect on pH
Time frame: During the 48hrs study period
Effect on heart rate
Time frame: During the 48hrs study period
Effect on blood pressure
Time frame: During the 48hrs study period
Effect on respiratory rate
Time frame: During the 48hrs study period
Effect on peripheral capillary oxygen saturation (SpO2)
Time frame: During the 48hrs study period
Effect on partial oxygen pressure (pO2)
Time frame: During the 48hrs study period
Effect on work of breathing (WOB)
Time frame: During the first 24hrs of the study period
Effect on pressure time product (PTP)
Time frame: During the first 24hrs of the study period
Effect on tumor necrosis factor (TNF)-alfa
Time frame: During the first 24hrs of the study period
Effect on interleukin(IL)-6 and IL-8
Time frame: During the first 24hrs of the study period
Amount of days on mechanical ventilation
Time frame: Until 30 days after the end of the study period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
L.M.A. Heunks, prof.dr. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rocuronium Bromide in people with Respiratory Insufficiency, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Diana Jansen, Drs. (+31(0)613225643, diana.jansen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2020.