Respiratory-Gated Imaging TechniquesPhase 4FRINeoSNCT02284412
Functional Respiratory Imaging After Neostigmine or Sugammadex
A Phase 4 study testing Neostigmine, Sugammadex and Water for injection in people with Respiratory-Gated Imaging Techniques, run by Onze Lieve Vrouw Hospital at 1 site in Belgium.
Trial summary
The use of neuromuscular blocking agents (NMBAs) is still associated with postoperative pulmonary complications. The investigators rely on acceleromyography (AMG) of a peripheral nerve/muscle to assess the patients' breathing capability at the end of surgery. Read more about this study
- Who is it for?
- Ages 3 to 6 months, men only
- Conditions the study is for
- Respiratory-Gated Imaging Techniques
- What is being tested?
- Neostigmine, Sugammadex and Water for injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteBelgium
- Study dates
- Dec 2014to Apr 2015
- 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 3 to 6 months
- Men only
- No healthy volunteers
- Child
Who may be able to join
- male Sprague-Dawley rats
Who cannot join
- N/A
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Visualization of Regional Lung Ventilation During Neostigmine or Sugammadex Enhanced Recovery From Moderate Residual Neuromuscular Blockade in the Anaesthetized Rat Using Functional Respiratory Imaging
The use of neuromuscular blocking agents (NMBAs) is still associated with postoperative pulmonary complications. The investigators rely on acceleromyography (AMG) of a peripheral nerve/muscle to assess the patients' breathing capability at the end of surgery. It is possible that respiratory complications after surgery (e.g. desaturation and atelectasis) are related to the lack of diaphragm activity.
A previous trial by our study group links the use of sugammadex, a novel selective relaxant binding agent (SRBA) for reversal of neuromuscular blockade, to an increase in diaphragm electrical activity, compared to reversal with neostigmine. Our hypothesis is that by making nicotinergic acetylcholine receptors free from rocuronium in the diaphragmatic neuromuscular junctions, instead of increasing the amount of acetylcholine (like neostigmine does), sugammadex will result in a better neuromuscular coupling. This may have its subsequent effects on the central control of breathing, influencing the balance between intercostal and diaphragm activity.
The investigators now propose a study in rats, where the investigators will use Functional Respiratory Imaging (FRI, property of FluidDA n.v., Groeningenlei 132, B-2550 Kontich) to assess regional lung ventilation after sugammadex, neostigmine or spontaneous reversal. The images obtained through micro-CT scans allow us to accurately reconstruct airway morphology in the free-breathing rat. It will provide us with new insights into breathing physiology after reversal of neuromuscular blockade.
Read the detailed description
This study is designed to assess the effect of sugammadex, neostigmine/glycopyrrolate and spontaneous reversal of a moderate rocuronium-induced neuromuscular blockade on regional lung ventilation. This is a randomized, controlled, parallel-group double blind trial in rats. A total of 18 adult male Sprague-Dawley rats will be used, 6 in each treatment group. The animals will be randomized in one of three groups, in a 1:1:1 ratio. This randomization will be performed according to a computer-generated randomization list. The first group will receive neostigmine/glycopyrrolate. The second group will receive sugammadex. The third group will receive water for injection. Reversal agents will be administered at a train-of-four (TOF) of 0.5, as measured with AMG.
The investigators will assess regional ventilation by means of micro-CT scanning during spontaneous breathing after the TOF ratio has reached ≥ 0.9. This way, the investigators can accurately reconstruct airway morphology. The different airway sections can then be linked to the corresponding lung tissue, and a full anatomical picture is thus rendered. A comparison of morphological scans at different breathing levels (e.g. end-inspiratory and end-expiratory) will allow us to model breath-by-breath regional airway and alveolar recruitment.
- Conditions
- Respiratory-Gated Imaging Techniques
- Being tested
- Neostigmine, Sugammadex, Water for injection
- Keywords
- Neostigmine, Sugammadex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeostigmineDrug
Also called Robinul-Neostigmine
At a train-of-four (TOF) ratio of 0.5: administration of neostigmine 0.06 mg/kg for reversal of neuromuscular blockade.
SugammadexDrug
Also called Bridion
At a train-of-four (TOF) ratio of 0.5: administration of sugammadex 15 mg/kg for reversal of neuromuscular blockade.
Water for injectionDrug
Also called Aqua ad iniectabilia
At a train-of-four (TOF) ratio of 0.5: administration of placebo for spontaneous recovery of neuromuscular blockade.
| Study group | Role | What they receive |
|---|---|---|
| neostigmine | Active comparator | Neostigmine will be dosed as 60 μg/kg, and glycopyrrolate 12 μg/kg (commercially available 5:1 co-formulation), as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade. Receives: Drug: Neostigmine |
| Sugammadex | Experimental | Sugammadex will be dosed 15 mg/kg, as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade. Receives: Drug: Sugammadex |
| Water for injection | Placebo comparator | Water will be dosed arbitrarily as a 1 mL single iv bolus administered over 10sec. Receives: Drug: Water for injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regional lung ventilation assessed by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
Comparison of the effect of sugammadex, neostigmine/glycopyrrolate and spontaneous recovery on regional lung ventilation in the spontaneously breathing rat, assessed by micro-CT scanning after recovery from neuromuscular block.
Measured: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.
Secondary outcomes (1)
Tidal volume (TV, mL) of breaths recorded by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
Comparison of the effect of sugammadex, neostigmine/glycopyrrolate and spontaneous recovery on tidal volume of breaths in the spontaneously breathing rat, assessed by micro-CT scanning after recovery from neuromuscular block.
Measured: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2014 (estimated)
- Study startDec 2014
- Primary completionDec 2014
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Respiratory-Gated Imaging TechniquesStudies of the same condition, open and under way.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Onze Lieve Vrouw Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Universiteit Antwerpen, MSD Belgium BVBA
- Responsible party
- Principal investigator, Guy CAMMU, Onze Lieve Vrouw Hospital
- Investigators
- GUY CAMMU, MD, PhD, Principal investigator, OLV Hospital, Aalst, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02284412
- Sponsor's protocol ID
- TSGC02
- Acronym
- FRINeoS
- Status last verified
- Apr 2015
- First submitted
- 28 Oct 2014
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103. doi: 10.1111/j.1399-6576.1997.tb04851.x.
PubMed 9366929Cammu GV, Smet V, De Jongh K, Vandeput D. A prospective, observational study comparing postoperative residual curarisation and early adverse respiratory events in patients reversed with neostigmine or sugammadex or after apparent spontaneous recovery. Anaesth Intensive Care. 2012 Nov;40(6):999-1006. doi: 10.1177/0310057X1204000611.
PubMed 23194209Grosse-Sundrup M, Henneman JP, Sandberg WS, Bateman BT, Uribe JV, Nguyen NT, Ehrenfeld JM, Martinez EA, Kurth T, Eikermann M. Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study. BMJ. 2012 Oct 15;345:e6329. doi: 10.1136/bmj.e6329.
PubMed 23077290Schepens T, Cammu G, Saldien V, De Neve N, Jorens PG, Foubert L, Vercauteren M. Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers. Eur J Anaesthesiol. 2015 Jan;32(1):49-57. doi: 10.1097/EJA.0000000000000140.
PubMed 25111539De Backer JW, Vos WG, Burnell P, Verhulst SL, Salmon P, De Clerck N, De Backer W. Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques. Anat Rec (Hoboken). 2009 May;292(5):720-7. doi: 10.1002/ar.20877.
PubMed 19322825Eikermann M, Zaremba S, Malhotra A, Jordan AS, Rosow C, Chamberlin NL. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth. 2008 Sep;101(3):344-9. doi: 10.1093/bja/aen176. Epub 2008 Jun 16.
PubMed 18559352
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Visualization of Regional Lung Ventilation During Neostigmine or Sugammadex Enhanced Recovery From Moderate Residual Neuromuscular Blockade in the Anaesthetized Rat Using Functional Respiratory Imaging
- ClinicalTrials.gov ID
- NCT02284412
- Acronym / sponsor ID
- FRINeoS / TSGC02
- Conditions
- Respiratory-Gated Imaging Techniques
- Keywords
- Neostigmine, Sugammadex
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Onze Lieve Vrouw HospitalUniversity, hospital or other
- Collaborators
- Universiteit Antwerpen, MSD Belgium BVBA
- Study start
- Dec 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 6 Nov 2014 (estimated)
- 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.
The use of neuromuscular blocking agents (NMBAs) is still associated with postoperative pulmonary complications. The investigators rely on acceleromyography (AMG) of a peripheral nerve/muscle to assess the patients' breathing capability at the end of surgery. It is possible that respiratory complications after surgery (e.g. desaturation and atelectasis) are related to the lack of diaphragm activity.
A previous trial by our study group links the use of sugammadex, a novel selective relaxant binding agent (SRBA) for reversal of neuromuscular blockade, to an increase in diaphragm electrical activity, compared to reversal with neostigmine. Our hypothesis is that by making nicotinergic acetylcholine receptors free from rocuronium in the diaphragmatic neuromuscular junctions, instead of increasing the amount of acetylcholine (like neostigmine does), sugammadex will result in a better neuromuscular coupling. This may have its subsequent effects on the central control of breathing, influencing the balance between intercostal and diaphragm activity.
The investigators now propose a study in rats, where the investigators will use Functional Respiratory Imaging (FRI, property of FluidDA n.v., Groeningenlei 132, B-2550 Kontich) to assess regional lung ventilation after sugammadex, neostigmine or spontaneous reversal. The images obtained through micro-CT scans allow us to accurately reconstruct airway morphology in the free-breathing rat. It will provide us with new insights into breathing physiology after reversal of neuromuscular blockade.
Detailed description
This study is designed to assess the effect of sugammadex, neostigmine/glycopyrrolate and spontaneous reversal of a moderate rocuronium-induced neuromuscular blockade on regional lung ventilation. This is a randomized, controlled, parallel-group double blind trial in rats. A total of 18 adult male Sprague-Dawley rats will be used, 6 in each treatment group. The animals will be randomized in one of three groups, in a 1:1:1 ratio. This randomization will be performed according to a computer-generated randomization list. The first group will receive neostigmine/glycopyrrolate. The second group will receive sugammadex. The third group will receive water for injection. Reversal agents will be administered at a train-of-four (TOF) of 0.5, as measured with AMG.
The investigators will assess regional ventilation by means of micro-CT scanning during spontaneous breathing after the TOF ratio has reached ≥ 0.9. This way, the investigators can accurately reconstruct airway morphology. The different airway sections can then be linked to the corresponding lung tissue, and a full anatomical picture is thus rendered. A comparison of morphological scans at different breathing levels (e.g. end-inspiratory and end-expiratory) will allow us to model breath-by-breath regional airway and alveolar recruitment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| neostigmine | Active comparator | Drug: NeostigmineNeostigmine will be dosed as 60 μg/kg, and glycopyrrolate 12 μg/kg (commercially available 5:1 co-formulation), as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade. |
| Sugammadex | Experimental | Drug: SugammadexSugammadex will be dosed 15 mg/kg, as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade. |
| Water for injection | Placebo comparator | Drug: Water for injectionWater will be dosed arbitrarily as a 1 mL single iv bolus administered over 10sec. |
Who may qualify
- Ages
- 3 to 6 months
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- male Sprague-Dawley rats
Key exclusion criteria (1 listed)
- N/A
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 |
|---|---|---|
| NeostigmineAlso: Robinul-NeostigmineAt a train-of-four (TOF) ratio of 0.5: administration of neostigmine 0.06 mg/kg for reversal of neuromuscular blockade. | Drug | neostigmine |
| SugammadexAlso: BridionAt a train-of-four (TOF) ratio of 0.5: administration of sugammadex 15 mg/kg for reversal of neuromuscular blockade. | Drug | Sugammadex |
| Water for injectionAlso: Aqua ad iniectabiliaAt a train-of-four (TOF) ratio of 0.5: administration of placebo for spontaneous recovery of neuromuscular blockade. | Drug | Water for injection |
Primary outcome
Regional lung ventilation assessed by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
Time frame: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.
Comparison of the effect of sugammadex, neostigmine/glycopyrrolate and spontaneous recovery on regional lung ventilation in the spontaneously breathing rat, assessed by micro-CT scanning after recovery from neuromuscular block.
1 secondary outcome
Tidal volume (TV, mL) of breaths recorded by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
Time frame: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
- Background: PubMed 9366929Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103. doi: 10.1111/j.1399-6576.1997.tb04851.x.
- Background: PubMed 23194209Cammu GV, Smet V, De Jongh K, Vandeput D. A prospective, observational study comparing postoperative residual curarisation and early adverse respiratory events in patients reversed with neostigmine or sugammadex or after apparent spontaneous recovery. Anaesth Intensive Care. 2012 Nov;40(6):999-1006. doi: 10.1177/0310057X1204000611.
- Background: PubMed 23077290Grosse-Sundrup M, Henneman JP, Sandberg WS, Bateman BT, Uribe JV, Nguyen NT, Ehrenfeld JM, Martinez EA, Kurth T, Eikermann M. Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study. BMJ. 2012 Oct 15;345:e6329. doi: 10.1136/bmj.e6329.
- Background: PubMed 25111539Schepens T, Cammu G, Saldien V, De Neve N, Jorens PG, Foubert L, Vercauteren M. Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers. Eur J Anaesthesiol. 2015 Jan;32(1):49-57. doi: 10.1097/EJA.0000000000000140.
- Background: PubMed 19322825De Backer JW, Vos WG, Burnell P, Verhulst SL, Salmon P, De Clerck N, De Backer W. Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques. Anat Rec (Hoboken). 2009 May;292(5):720-7. doi: 10.1002/ar.20877.
- Background: PubMed 18559352Eikermann M, Zaremba S, Malhotra A, Jordan AS, Rosow C, Chamberlin NL. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth. 2008 Sep;101(3):344-9. doi: 10.1093/bja/aen176. Epub 2008 Jun 16.
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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.
GUY CAMMU, MD, PhD principal investigator
OLV Hospital, Aalst, Belgium
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 Neostigmine, Sugammadex and Water for injection in people with Respiratory-Gated Imaging Techniques, run by Onze Lieve Vrouw Hospital at 1 site in Belgium.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 21 Apr 2015. 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 Belgium. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional lung ventilation assessed by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block. (time frame: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02284412, which also lists 6 linked publications.
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 21 Apr 2015.