ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000625370

Ethics application status

Approved

Date submitted

3/03/2017

Date registered

1/05/2017

Date last updated

1/05/2017

Type of registration

Retrospectively registered

Titles & IDs

Public title

Comparison of neuromuscular monitorings (TOF-Watch SX versus Philips NMT Module) in patients undergoing rhinoplasty or rhinoseptoplasty.

Scientific title

Investigation protocol comparing two quantitative modules for monitoring peroperative neuromuscular transmission in patients undergoing rhinoplasty or rhinoseptoplasty under general anaesthesic: TOF-Watch SX versus Philips NMT module.

Secondary ID [1]

None

Universal Trial Number (UTN)

None

Trial acronym

None

Linked study record

None

Health condition

Health condition(s) or problem(s) studied:

patients undergoing rhinoplasty or rhinoseptoplasty under general anaesthesic

Condition category

Condition code

Anaesthesiology

Anaesthetics

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

This investigation protocol seeks to compare the results obtained in clinical practice in curarised patients using two monitoring modules currently marketed (in line with EU standards):
The results obtained simultaneously by the Philips Intellivue NMT module (Philips, The Netherlands) on a patient's hand will be compared with those obtained by the TOF-Watch SX (Organon, The Netherlands) fitted to their other hand stabilised in the SL TOF tube, an association which has demonstrated the adequacy of its results compared with mechanomyography, the established reference method.
The investigation focusses on a cohort of 30 patients aged 18 to 80, classified ASA I or II and undergoing rhinoplasty or rhinoseptoplasty under general anaesthetic. .
The patient's height, weight, age and sex are recorded in the protocol, as is their dominant hand (left or right) to define the population investigated.
As premedication, the patient receives Alprazolam 0.5 mg an hour before they go to theatre. On arrival in theatre, the patient is conventionally monitored with a saturometer, an electrocardiogram with three or five derivations depending on their antecedents, and their blood pressure is measured non-invasively, scheduled in automatic mode with constant measurements at five-minute intervals.
An intravenous drip (18G catheter) is inserted into their forearm or elbow, for intravenous perfusion of Plasmalyte 500 ml as the first perfusion.
The module to monitor neuromuscular transmission using acceleromyography is connected (non-invasive and non-traumatic) to both hands as shown in the illustration. We observe the criteria for good clinical practice for pharmaco-dynamic investigations as proposed by Fuchs-Buder. The skin is cleaned with diethylether and two ECG skin electrodes are placed along the route of the ulnar nerve on each wrist.
The arm on which the Philips Intellivue NMT module is placed is left free of any specific installation as recommended in its user manual, whilst the forearm on which the AMG TOF-Watch SX is placed is positioned in the SL TOF Tube and this is thus considered the reference curarisation monitoring module.
The arms are then placed alongside the body in "spoon"-type arm supports with a thick layer of gel to protect nerve structures.
Once all monitoring modules are in place, the patient is pre-oxygenated using pure oxygen, FiO2 100% at a rate of 8 l/min.
The general anaesthetic is induced with continuous intravenous infusion of Remifentanyl 0.25 gamma/kg/min, and continuous infusion of Propofol 1% to obtain a theoretical plasma concentration of 3 to 4 gamma/cc (Diprifusor Cardinal Health, Basingstoke, UK) and Linisol 2% 1 mg/kg as an intravenous bolus. As soon as the patient loses consciousness, they are manually ventilated.
Now, simultaneously with each NMT monitoring module, we can automatically investigate the supra-maximum stimulation threshold and 100% calibration of initial responses. The amperages determined by the two devices (+/- 50 mA) are recorded.
Each ulnar nerve is stimulated simultaneously using a Train of Four (4 electric stimulations at 2 Hz, Train of Four, TOF) repeated at 15-second intervals.
Four successive base value measurements for the TOF ratio (T4/T1 ratio) are recorded for each curarisation monitoring module, simultaneously, and their averages determine the reference values before curarisation. We calculate 90% of this base value to determine the neuromuscular blocking recovery threshold for each monitoring module using the following formula:
Normalised TOF ratio 90% = sum of 4 TOF ratio × 9/40 with a result rounded up.

With the baseline determined, the patient is curarised with administration of rocuronium 0.5 mg/kg. The theatre time is noted as the reference time (hh:mm:ss). Non-invasive automatic blood pressure measurement is suspended during the neuromuscular blocking induction phase so as not to limit the distribution of the Rocuronium in either of the two arms.
So we expect to each a state of deep curarisation, with a TOF count of 0. Again, the exact time is recorded when the TOF count of 0 is reached using the TOF-Watch and when it is reached using the Philips NMT (onset duration).
The patient is then conventionally intubated, eye protection is put in place, the tube is fitted and assisted ventilation in "Controlled volume" mode is begun, followed by the surgical equipment.
Post-Tetanic-Count (PTC: automatic stimulation sequence including 50 Hz tetanic stimulation for 5 seconds adapted to monitor deep neuromuscular blocking) is then measured with each monitoring module at the same time (hours - minutes -seconds noted). After a free period of 3 minutes, TOF stimulation mode is launched every 15 seconds.
Anaesthesia is maintained with continuous intravenous administration of Remifentanyl 0.15 gamma/kg/min and Propofol 1% in AIVOC mode with a target plasma concentration of 2 to 4 gamma/cc. Neither Magnesium, nor halogenated vapour, nor a further bolus of rocuronium is administered (to prevent potentialisation of neuromuscular blocking by these agents).
We then continuously observe via the TOF spontaneous recovery of neuromuscular blocking with successive, simultaneous measurements (every 15 seconds) using the two curarisation monitoring modules.
The investigation seeks to confirm (or otherwise) the similarity between the results obtained using each monitoring module.

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

Neuromuscular monitoring comparison : Philips NMT module compared with TOF-Watch SX (considered the reference).

Control group

Active

Outcomes

Primary outcome [1]

Initial TOF ratios are recorded with 4 successive measurements before rocuronium is administered. The average of the 4 measurements determines the initial baseline. These baselines obtained by the Philips NMT module and the TOF-Watch SX are compared for each patient.

Timepoint [1]

As soon as the patient loses consciousness, they are manually ventilated. Simultaneously with each NMT monitoring module, we can automatically investigate the supra-maximum stimulation threshold and 100% calibration of initial responses. The amperages determined by the two devices (+/- 50 mA) are recorded.
Each ulnar nerve is stimulated simultaneously, repeated at 15-second intervals for the duration of the surgery.

Secondary outcome [1]

TOF ratio 90% are recorded on each device and they are compared.

Timepoint [1]

Eligibility

Key inclusion criteria

- aged 18 to 80,
- classified ASA I or II,
- undergoing rhinoplasty or rhinoseptoplasty under general anaesthetic

Minimum age

18 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

- pregnant and breastfeeding women,
- patients with renal or hepatic insufficiency,
- patients with neurological deficit,
- patients with a suspected allergy to the drugs used in the protocol or receiving treatment which will interfere with neuromuscular transmission

Study design

Purpose

Screening

Duration

Cross-sectional

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Baseline analysis: definition and comparison of levels and repeatability factors.
Initial TOF ratios are recorded with 4 successive measurements before rocuronium is administered. The average of the 4 measurements determines the initial baseline. These baselines obtained by the Philips NMT module and the TOF-Watch SX are compared for each patient using a Wilcoxon Rank Sum test. Repeatability factors (1.96v2 SD) are compared using a z test, a low factor indicating little variability between consecutive measurements. P<0.05 is considered significant.
The same comparative analysis is conducted once a final baseline has stabilised, ensured with administration of 100 mg of Sugammadex after recovery of a normalised TOF ratio of 90%. The initial and final baselines will be compared using a Wilcoxon Rank Sum test. P<0.05 is considered significant.

Analysis of neuromuscular blocking recovery profiles: performance of the Philips NMT module compared with the TOF-Watch SX (considered the reference).
In the different neuromuscular blocking scores (PTC, TOF count 2, TOF ratio 50%, TOF ratio 90% and normalised TOF ratio 90%), 4 consecutive, simultaneous measurements are recorded on each device when the value concerned is reached on the TOF-Watch SX, but also when the TOF ratio 90% (gross and normalised) is reached with the Philips NMT module. These results are compared using a Wilcoxon Rank Sum test, p<0.05 significant. The bias and the agreement limits of the two devices with different scores considered are also determined using the method described by Bland and Altman.

Sample determination is considered in light of recovery of the TOF ratio 90%, the critical safety threshold for orotracheal extubation.
Considering a risk a of 0.05 and a power 1-beta of 95, and for variability (DS) observed on a pre-series of 17.5%, we must recruit 30 patients so that a difference of 10% using the two measurements does not escape us.
The statistical analyses were carried out with SPSS Registered Trademark 15.0 statistical software (SPSS Inc., Chicago, Ill) and G*Power 3.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

14/02/2017

Date of last participant enrolment

Anticipated

10/05/2017

Actual

Date of last data collection

Anticipated

11/05/2017

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

Belgium

State/province [1]

Namur

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

CHU UCL Namur - Mont-Godinne

Address [1]

Gaston Therasse Street, 1
5530 Yvoir

Country [1]

Belgium

Primary sponsor type

Hospital

Name

CHU UCL Namur - Mont-Godinne

Address

Gaston Therasse Street, 1
5530 Yvoir

Country

Belgium

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Ethics Committee of CHU UCL Namur

Ethics committee address [1]

Gaston Therasse Avenue, 1
5530 Yvoir

Ethics committee country [1]

Belgium

Date submitted for ethics approval [1]

26/12/2016

Approval date [1]

14/02/2017

Ethics approval number [1]

Summary

Brief summary

The reliability of monitoring of neuromuscular transmission used during surgery requiring curarisation (or neuromuscular blocking) is key to ensuring patient safety and optimum operating conditions. However, in clinical practice, the results obtained using devices provided by the industry are not always credible.
This investigation protocol seeks to compare the results obtained in clinical practice in curarised patients using two monitoring modules currently marketed (in line with EU standards):
The results obtained simultaneously by the Philips Intellivue NMT module (Philips, The Netherlands) on a patient's hand will be compared with those obtained by the TOF-Watch SX (Organon, The Netherlands) fitted to their other hand stabilised in the SL TOF tube, an association which has demonstrated the adequacy of its results compared with mechanomyography, the established reference method.
In fact, although they use the same measuring principle (acceleromyography), the results obtained using the two devices appear to be quite different, especially during the final phase of recovery from neuromuscular blocking. Confirmation of a minimum recovery threshold (TOF ratio 90%) is essential if we are to rule out any residual curarisation and provide patients with optimum conditions of safety during tracheal extubation and when waking them. Any significant difference (more than 10%) between the inherent results obtained using the two devices would have significant clinical implications. In fact, recovery of the TOF ratio 80% is quite insufficient in comparison at 90%

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Dubois Virginie

Address

CHU UCL Namur Godinne
Gaston Therasse Avenue, 1
5530 Yvoir

Country

Belgium

Phone

+32 81 423910

Fax

[email protected]

Contact person for public queries

Name

Dr Ibsen Arni

Address

CHU UCL Namur Godinne
Gaston Therasse Avenue, 1
5530 Yvoir

Country

Belgium

Phone

+32 81 423911

Fax

[email protected]

Contact person for scientific queries

Name

Prof Dubois Philippe

Address

CHU UCL Namur Godinne
Gaston Therasse Avenue, 1
5530 Yvoir

Country

Belgium

Phone

+32 81 42 39 29

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Philips Intellivue NMT module: precision and performance improvements to meet the clinical requirements of neuromuscular block management.	2020	https://dx.doi.org/10.1007/s10877-019-00287-y

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically