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Trial registered on ANZCTR


Registration number
ACTRN12614000108617
Ethics application status
Approved
Date submitted
18/01/2014
Date registered
29/01/2014
Date last updated
17/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Reversal of rocuronium with neostigmine or sugammadex in high risk elderly patients: prospective randomized investigation of postoperative outcome
Scientific title
A randomised controlled trial evaluating the effects of neostigmine vs. sugammadex-based reversal of rocuronium on postoperative morbidity and mortality in high risk elderly patients
Secondary ID [1] 283928 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Reversal of rocuronium induced neuromuscular block in high risk elderly patients 290937 0
Condition category
Condition code
Anaesthesiology 291292 291292 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Once all inclusion criteria have been fulfilled and all exclusion criteria have been excluded, a dedicated research assistant with no further data collection duties will access the randomisation website in order to randomize the patient to either:

Sugammadex 2mg/k (intervention group) or:
Neostigmine 0.05 mg/kg + atropine 0.015 mg/kg


Theatre
Patients will then proceed to have surgery and should at least receive rocuronium 0.6 mg/kg on induction of anaesthesia. Further doses of rocuronium (5-20 mg) will be administered if required to maintain a train of four (TOF) count of 1-2 twitches until the end of surgery.

Both total intravenous or volatile based anaesthetic techniques may be used. Opioids used may be fentanyl, remifentanil, alfentanil, sufentanil, morphine and hydromorphone.

TOF monitoring: in-theatre monitoring may be quantitative (preferred!) or qualitative (simple nerve stimulator). TOF is monitored intra-operatively at least every 5 min in order to maintain a TOF count of 1-2 (max!). At the end of the operation, at discretion of the attending anaesthetist the study reversal drug (anaesthetist blinded) is administered intravenously over 10 seconds and the time of administration noted. Subsequent TOF monitoring is not compulsory and fully at the discretion of the attending anaesthetist.

30 min prior to extubation all patients receive 4 mg ondansetron intravenously as antiemetic prophylaxis.

After extubation the patient is transferred to the postoperative acute care unit (PACU) (or a high dependency area of similar quality, i.e.: intensive care unit or high dependency unit) where 6 l oxygen will be applied via a Hudson face mask.
Intervention code [1] 288622 0
Treatment: Drugs
Comparator / control treatment
neostigmine 0.05 mg/kg + atropine 0.015 mg/kg reversal of neuromuscular block
Control group
Active

Outcomes
Primary outcome [1] 291286 0
pulmonary outcome score (pulmonary outcome score 0-100 points- equally based on the 4 parameters: body temp. greater than 38 C, leucocyte count greater than 11.000 microlitre-1, physical examination consistent with pneumonia and shortness of breath)
Timepoint [1] 291286 0
postoperative day 1,3 and 7
Secondary outcome [1] 306428 0
Time from skin closure to extubation
Timepoint [1] 306428 0
postoperatively
Secondary outcome [2] 306502 0
Time from administration of the reversal agent to extubation
Timepoint [2] 306502 0
postoperatively
Secondary outcome [3] 306503 0
Incidence of postoperative nausea and vomiting in the recovery room
Timepoint [3] 306503 0
during stay in recovery room (assessed via recovery nurse/physician observation)
Secondary outcome [4] 306504 0
Incidence of desoxygenation (SpO2 less than 95%, 90%, 85%) with patients on 6l oxygen via Hudson mask
Timepoint [4] 306504 0
during stay in the recovery room, assessed by nurse/physician
Secondary outcome [5] 306505 0
Incidence of aspiration
Timepoint [5] 306505 0
in the recovery room, assessed by nurse/physician
Secondary outcome [6] 306506 0
Incidence of clinical symptoms potentially associated with residual blockade (diplopia, difficulty in swallowing, feeling of general weakness) in PACU
Timepoint [6] 306506 0
during stay in the recovery room, assessed by nurse/physician
Secondary outcome [7] 306507 0
Incidence of airway obstruction; need for airway aids such as oropharyngeal or nasopharyngeal tubes, incidence of re-intubation in PACU
Timepoint [7] 306507 0
during stay in the recovery room, assessed by nurse/physician
Secondary outcome [8] 306508 0
Incidence of unplanned ICU admissions
Timepoint [8] 306508 0
postoperatively
Secondary outcome [9] 306510 0
Patient satisfaction with anaesthesia and recovery rating on 0-10 numeric rating scale (NRS)
Timepoint [9] 306510 0
at recovery room discharge and on postoperative day 3, assessed by research assistant
Secondary outcome [10] 306511 0
Length of recovery room stay and length of in-hospital stay
Timepoint [10] 306511 0
postoperatively
Secondary outcome [11] 306515 0
Incidence of antibiotic treatment due to airway morbidity within 7 postoperative days.
Timepoint [11] 306515 0
within 7 postoperative days, assessed via written patient notes by research assistant
Secondary outcome [12] 306516 0
Incidence and results of chest x-rays or ct scans performed within 7 postoperative days
Timepoint [12] 306516 0
within 7 postopertative days, reported by radiologist, data collected via research assistant
Secondary outcome [13] 306517 0
30 day postoperative mortality
Timepoint [13] 306517 0
collected by research assistand after 30 postoperative days

Eligibility
Key inclusion criteria
Patients scheduled for elective or urgent (non-emergency) surgery ASA risk category 3 or 4, greater than or equal to 75 years of age, paralysed with rocuronium and extubated at the end of surgery.
Minimum age
75 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Emergency (equals immediate) surgery, incapacity to consent to study participation, aspiration/significant atelectasis or active pneumonia within 7 preoperative days, planned to remain intubated at the end of surgery, all cardio-thoracic patients and all patients with significant chest trauma, contraindication to one of the study drugs or rocuronium, known severe neuropathy or myopathy affecting airway maintenance, breathing and neuromuscular monitoring, history of stroke with ongoing paresis, sepsis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After screening and fulfilment of all inclusion and nil exclusion criteria randomization will be performed via a central randomization website (randomization via randomly permuted blocks). Website will allocate 1 specific treatment arm: neostigmine or sugammadex. Allocation will only been known to randomizing person accessing the website. The attending anaesthetist as well as all persons collecting postoperative data shall remail blinded to the allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomly permuted blocks
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis
A recent retrospective investigation involving 1444 patients showed a significant benefit for pulmonary outcome in high risk elderly patients when reversed with sugammadex vs neostigmine (1). The sample size calculation for the proposed study is based on the latter investigation:

To detect a differences in pulmonary outcome a pulmonary outcome score is used (0-100 points; equally based on the 4 parameters “body temp. greater than 38 C”, “leucocyte count greater than 11.000 microlitre-1”, “physical examination consistent with pneumonia” and “shortness of breath”). In order to identify differences in outcome score values of 1% or more with a power of greaten than 95% (CI 0.90-0.98) 180 patients will need to be randomized in either “neostigmine” or “sugammadex” reversal (n equals 90 each group). This number allows for a 20% “loss” of patients after initial inclusion (e.g. unexpectedly admitted to ICU intubated).

For comparison of categorical data, the chi-square and Fisher’s exact test will be used. Numerical data will be compared using ANOVA, the Mann-Whitney-U or the Kruskal-Wallis-H test, as appropriate. Multiple linear regression analysis will be used to investigate confounding factors on patient outcome and for the analysis of the ‘pulmonary outcome score’ (see above).


References

1. Ledowski T et al. Eur J Anaesth 2013; in press (accepted 24.9.2013)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/03/2014
Actual
9/05/2014
Date of last participant enrolment
Anticipated
30/12/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
180
Accrual to date
168
Final
Recruitment outside Australia
Country [1] 5755 0
Korea, Republic Of
State/province [1] 5755 0
Seoul
Country [2] 5756 0
Netherlands
State/province [2] 5756 0
Groningen
Country [3] 5757 0
Malaysia
State/province [3] 5757 0
Kuala Lumpur
Country [4] 9157 0
Hungary
State/province [4] 9157 0
Debrecen

Funding & Sponsors
Funding source category [1] 288570 0
University
Name [1] 288570 0
University of Western Australia
Country [1] 288570 0
Australia
Primary sponsor type
Individual
Name
Thomas Ledowski
Address
University of Western Australia
Level 2 RPH MRF Building
Rear 50 Murray Street
Perth WA 6000
Country
Australia
Secondary sponsor category [1] 287281 0
None
Name [1] 287281 0
none
Address [1] 287281 0
Country [1] 287281 0
Other collaborator category [1] 277763 0
Individual
Name [1] 277763 0
Prof. Hans de Boer
Address [1] 277763 0
Department of Anesthesiology and Pain Medicine
Martini General Hospital Groningen
PO Box 30033
9700 RM Groningen
the Netherlands
Country [1] 277763 0
Netherlands
Other collaborator category [2] 277765 0
Individual
Name [2] 277765 0
Dr. Ina Ismiarti Shariffuddin
Address [2] 277765 0
Dept of Anaesthesia & Intensive Care,
Faculty of Medicine,
University Malaya,
Jalan Lembah Pantai,
50603 Kuala Lumpur,
Country [2] 277765 0
Malaysia
Other collaborator category [3] 277766 0
Individual
Name [3] 277766 0
Prof. H.S. Yang
Address [3] 277766 0
Dept. of Anaesthesiology
Asan Medical Centre
388-1 Pungnap 2(i)-dong, Songpa-gu, Seoul, South Korea
Country [3] 277766 0
Korea, Republic Of
Other collaborator category [4] 277781 0
Individual
Name [4] 277781 0
Dr Pui San Loh
Address [4] 277781 0
Dept of Anaesthesia & Intensive Care,
Faculty of Medicine,
University Malaya,
Jalan Lembah Pantai,
50603 Kuala Lumpur,
Country [4] 277781 0
Malaysia
Other collaborator category [5] 277782 0
Individual
Name [5] 277782 0
Prof. Lucy Chan
Address [5] 277782 0
Dept of Anaesthesia & Intensive Care,
Faculty of Medicine,
University Malaya,
Jalan Lembah Pantai,
50603 Kuala Lumpur,
Country [5] 277782 0
Malaysia
Other collaborator category [6] 279679 0
Individual
Name [6] 279679 0
Prof. Bela Fulsedi
Address [6] 279679 0
Dept. of Anesthesiology and Intensive Care Medicine
University Debrecen
4032 Debrecen, Nagyerdei krt 94
Hungary
Country [6] 279679 0
Hungary

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290430 0
Ethics Committee of the ASAN Medical Centre
Ethics committee address [1] 290430 0
Ethics committee country [1] 290430 0
Korea, Republic Of
Date submitted for ethics approval [1] 290430 0
13/01/2014
Approval date [1] 290430 0
01/04/2014
Ethics approval number [1] 290430 0
Ethics committee name [2] 290431 0
Ethics Committee of the Martini HOspital
Ethics committee address [2] 290431 0
Ethics committee country [2] 290431 0
Netherlands
Date submitted for ethics approval [2] 290431 0
14/02/2014
Approval date [2] 290431 0
Ethics approval number [2] 290431 0
Ethics committee name [3] 290432 0
Ethics Committee of the University of Malaya
Ethics committee address [3] 290432 0
Ethics committee country [3] 290432 0
Malaysia
Date submitted for ethics approval [3] 290432 0
21/02/2014
Approval date [3] 290432 0
15/05/2014
Ethics approval number [3] 290432 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45670 0
Prof Thomas Ledowski
Address 45670 0
School of Medicine and Pharmacology
University of Western Australia
Level 2 RPH MRF Building
Rear 50 Murray Street
Perth WA 6000
Country 45670 0
Australia
Phone 45670 0
+61 8 92241036
Fax 45670 0
Email 45670 0
thomas.ledowski@health.wa.gov.au
Contact person for public queries
Name 45671 0
Thomas Ledowski
Address 45671 0
School of Medicine and Pharmacology
University of Western Australia
Level 2 RPH MRF Building
Rear 50 Murray Street
Perth WA 6000
Country 45671 0
Australia
Phone 45671 0
+61 8 92241036
Fax 45671 0
Email 45671 0
thomas.ledowski@health.wa.gov.au
Contact person for scientific queries
Name 45672 0
Thomas Ledowski
Address 45672 0
School of Medicine and Pharmacology
University of Western Australia
Level 2 RPH MRF Building
Rear 50 Murray Street
Perth WA 6000
Country 45672 0
Australia
Phone 45672 0
+61 8 92241036
Fax 45672 0
Email 45672 0
thomas.ledowski@health.wa.gov.au

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
SourceTitleYear of PublicationDOI
EmbaseReversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients.2021https://dx.doi.org/10.1016/j.bja.2021.04.026
N.B. These documents automatically identified may not have been verified by the study sponsor.