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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02284412
Other study ID # TSGC02
Secondary ID
Status Completed
Phase Phase 4
First received October 28, 2014
Last updated April 20, 2015
Start date December 2014
Est. completion date April 2015

Study information

Verified date April 2015
Source Onze Lieve Vrouw Hospital
Contact n/a
Is FDA regulated No
Health authority Belgium: Federal Agency for Medicines and Health Products, FAMHP
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 13
Est. completion date April 2015
Est. primary completion date December 2014
Accepts healthy volunteers No
Gender Male
Age group 3 Months to 6 Months
Eligibility Inclusion Criteria:

- male Sprague-Dawley rats

Exclusion Criteria:

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Respiratory-Gated Imaging Techniques

Intervention

Drug:
Neostigmine
At a train-of-four (TOF) ratio of 0.5: administration of neostigmine 0.06 mg/kg for reversal of neuromuscular blockade.
Sugammadex
At a train-of-four (TOF) ratio of 0.5: administration of sugammadex 15 mg/kg for reversal of neuromuscular blockade.
Water for injection
At a train-of-four (TOF) ratio of 0.5: administration of placebo for spontaneous recovery of neuromuscular blockade.

Locations

Country Name City State
Belgium OLV Hospital Aalst

Sponsors (3)

Lead Sponsor Collaborator
Onze Lieve Vrouw Hospital MSD Belgium BVBA, Universiteit Antwerpen

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

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. — View Citation

Cammu 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. — View Citation

De 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. — View Citation

Eikermann 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. — View Citation

Grosse-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. — View Citation

Schepens 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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. CT scanning will take between 5 to 8 minutes, followed by post-processing of the images. Yes
Secondary 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. CT scanning will take between 5 to 8 minutes, followed by post-processing of the images. Yes