Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000063415
Ethics application status
Approved
Date submitted
19/01/2016
Date registered
21/01/2016
Date last updated
4/11/2022
Date data sharing statement initially provided
3/12/2018
Date results information initially provided
4/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of sugammadex on respiratory complications and patient satisfaction following surgery
Scientific title
Does the use of sugammadex for reversal of paralysis reduce postperative pulmonary events when compared with neostigmine following general anaesthesia
Secondary ID [1] 288111 0
nil known
Universal Trial Number (UTN)
U1111-1177-4335
Trial acronym
P-PERSoN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Complications of Surgery 296976 0
Patient Quality of Recovery 296977 0
Recovery Room Complications Post Surgery 296979 0
Postoperative Nausea and Vomiting 296981 0
Condition category
Condition code
Anaesthesiology 297233 297233 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2mg/kg intravenous sugammadex at completion of surgery
Intervention code [1] 293418 0
Treatment: Drugs
Comparator / control treatment
0.5mg/kg neostigmine and 0.01mg/kg glycopyrullate at completion of surgery.
Control group
Active

Outcomes
Primary outcome [1] 296815 0
Any of the following postoperative pulmonary complications (as defined by the ARISCAT group) - composite outcome; 1. Respiratory failure – Postoperative Pao2 <60 mmHg on room air, a ratio of Pao2 to inspired oxygen fraction <300, or arterial oxyhemoglobin saturation measured with pulse oximetry <90% and requiring oxygen therapy 2. Suspected pulmonary infection; Treatment with antibiotics for a respiratory infection, plus at least one of the following criteria: New or changed sputum, New or changed lung opacities on a clinically indicated chest radiograph, Temperature >38.3°C, Leukocyte count >12,000/mm 3. Pleural effusion - Chest radiograph demonstrating blunting of the costophrenic angle, loss of the sharp silhouette of the ipsilateral hemidiaphragm (in upright position), evidence of displacement of adjacent anatomical structures, or (in supine position) a hazy opacity in one hemithorax with preserved vascular shadows 4. Atelectasis - Suggested by lung opacification with shift of the mediastinum, hilum, or hemidiaphragm toward the affected area, and compensatory overinflation in the adjacent nonatelectatic lung 5. Pneumothorax - Air in the pleural space with no vascular bed surrounding the visceral pleura 6. Bronchospasm - Newly detected expiratory wheezing treated with bronchodilators 7. Aspiration pneumonitis - Respiratory failure after the inhalation of regurgitated gastric contents
Timepoint [1] 296815 0
day 1 and 2 postoperatively and at hospital discharge
Secondary outcome [1] 319446 0
Quality of Recovery Score (QoR-15)
Timepoint [1] 319446 0
Day 1 and 30 post operatively
Secondary outcome [2] 319447 0
Post operative nausea and vomiting score
1 – no PONV
2 – PONV responsive to antiemetics
3 – PONV unresponsive to antiemetics
Timepoint [2] 319447 0
During Recovery Room Stay
Secondary outcome [3] 319448 0
Mortality
Timepoint [3] 319448 0
30-day
Secondary outcome [4] 319449 0
Patient reported ‘chest infection’ requiring antibiotics since operation or patient reported need for NEW or INCREASED bronchodilator therapy since operation (at follow up phone call).
Timepoint [4] 319449 0
30 day
Secondary outcome [5] 319450 0
Proportion of patient that exhibit one or more of the following PACU Events (recorded by recovery room nursing staff);
1. Any desaturation to SpO2<90%
2. Need for manual airway support
3. Need for oropharyngeal or nasopharyngeal airway
4. Need for reintubation in PACU
5. Need for anaesthetist to review the patient
6. Unplanned ICU admission
Timepoint [5] 319450 0
During Recovery Room Stay
Secondary outcome [6] 319451 0
Hospital Stay, recorded from medical record.
Timepoint [6] 319451 0
days (assessed at 30 days from medical record)

Eligibility
Key inclusion criteria
age >18
patients presenting for non-cardiac surgery
planned operative time of over 2 hours
plan to be intubated and to receive muscle relaxants for their surgery
plan to stay at least one night in hospital
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous recruitment to the trial
Patient refusal
Weight>200kg
Planned postoperative intubation and ventilation
Hypersensitivity reactions to any of the study drugs
Mechanical obstruction of the intestinal or urinary tracts
Peritonitis
Liver failure with Child-Pugh class B/C
Renal failure with either regular peritoneal or haemodialysis or serum creatinine >140mcgmol/L

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Treating Anaesthetist and staff assessing outcomes blinded to treatment. Randomisation will be via computer generated numbers, which will be sealed in opaque, sequentially numbered envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation to group.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The largest prospective study looking at a defined set of postoperative pulmonary complications showed an overall incidence of 7.9%. Based on a conservative estimate of 7% baseline incidence and a conservative estimate that sugamamdex can reduce this to 3% (based on our retrospective study showing an odds reduction of 0.28, which would reduce the incidence to 1.96%) would produce a clinically relevant NNT of 29. Accepting an alpha error of 0.05 and beta error of 0.2 would require 930 patients. Allowing for 5% incomplete data and loss to follow up requires 976 patients.

Statistical analysis will be performed based on the outcome.
1. PPC rate, QoR-40 score, hospital stay will be assessed as continuous variables
2. PONV score will be assessed as an ordinal variable
3. Mortality and the presence of respiratory and PACU events will be assessed as categorical variables

The effect of sugammadex on continuous variables will be analysed by 2-tailed Student T-test
The effect of sugammadex on ordinal and categorical variables will be analysed by Chi-squared tests
Binomial regression analysis will be performed on the categorical outcomes for the subgroup analyses. Logistic regression will be performed to analyse the effect of PONV risk on PONV scores.

Statistical tests appropriate to confirm test assumptions are met will be performed.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Other reasons/comments
Other reasons
COVID stopped recruitment for 18 months
Date of first participant enrolment
Anticipated
1/04/2017
Actual
3/12/2018
Date of last participant enrolment
Anticipated
1/01/2019
Actual
1/01/2019
Date of last data collection
Anticipated
31/01/2019
Actual
31/01/2020
Sample size
Target
976
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5094 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 7462 0
North Shore Private Hospital - St Leonards
Recruitment postcode(s) [1] 12558 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [2] 15288 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 292721 0
Other
Name [1] 292721 0
Northern Sydney Anaesthetic Research Institute (NSARI)
Country [1] 292721 0
Australia
Primary sponsor type
Other
Name
Northern Sydney Anaesthetic Research Institute (NSARI)
Address
C/- Dept of Anaesthesia, Level 4
Royal North Shore Hospital,
Reserve Rd,
St Leonards,
2065
Country
Australia
Secondary sponsor category [1] 291453 0
None
Name [1] 291453 0
None
Address [1] 291453 0
None
Country [1] 291453 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294210 0
Northern Sydney Local Health District Human Research Ethics Committee (NSLHD HREC)
Ethics committee address [1] 294210 0
Level 13 Kolling Building
Royal North Shore Hospital
Reserve Rd
St Leonards NSW 2065
Ethics committee country [1] 294210 0
Australia
Date submitted for ethics approval [1] 294210 0
01/03/2016
Approval date [1] 294210 0
27/01/2017
Ethics approval number [1] 294210 0
HREC/16/HAWKE/433

Summary
Brief summary
In anaesthesia, traditional agents used for the reversal of paralytic agents are designed around the use of an anticholinesterase inhibitor (commonly neostigmine) to increase motor end plate acetylcholine. This is usually combined with an anti-muscarinic agent (atropine or glycopyrullate) to offset the autonomic effects of excess acetylcholine. Sugammadex is a newer agent that works via encapsulation of aminosteroid neuromuscular blocking agents. Whether or not sugammadex is superior to neostigmine based techniques in terms of prevention of the morbidity associated with residual paralysis have never been shown in a prospective randomised trial. P-PERSoN is a prospective multi-centre, double blinded, randomised controlled trial to compare neostigmine/glycopyrullate and sugammadex reversal. The primary outcome is all in-hospital respiratory events. Secondary outcomes will be, recovery room airway and desaturation events, hospital stay, quality of recovery scores, all-cause 30-day mortality and respiratory morbidity.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62082 0
Dr Benjamin Olesnicky
Address 62082 0
c/- Dept of Anaesthesia, Level 4,
Royal North Shore Hospital,
Reserve Rd, St Leonards, NSW 2065
Country 62082 0
Australia
Phone 62082 0
+61 2 9463 2488
Fax 62082 0
Email 62082 0
[email protected]
Contact person for public queries
Name 62083 0
Dr Benjamin Olesnicky
Address 62083 0
c/- Dept of Anaesthesia, Level 4,
Royal North Shore Hospital,
Reserve Rd, St Leonards, NSW 2065
Country 62083 0
Australia
Phone 62083 0
+61 2 9463 2488
Fax 62083 0
Email 62083 0
[email protected]
Contact person for scientific queries
Name 62084 0
Dr Benjamin Olesnicky
Address 62084 0
c/- Dept of Anaesthesia, Level 4,
Royal North Shore Hospital,
Reserve Rd, St Leonards, NSW 2065
Country 62084 0
Australia
Phone 62084 0
+61 2 9463 2488
Fax 62084 0
Email 62084 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17537Clinical study reportBenjamin Olesnicky, Matthew Doane, Clare Farrell, Greg Knoblanche, Anthony Delaney, "Prevention of Postoperative Events following Reversal with Sugammadex or Neostigmine (the P-PERSoN Trial): Pilot Data Following Early Termination of a Prospective, Blinded, Randomised Trial", Anesthesiology Research and Practice, vol. 2022, Article ID 4659795, 8 pages, 2022. https://doi.org/10.1155/2022/4659795 



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Benjamin Olesnicky, Matthew Doane, Clare Farrell, ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePrevention of Postoperative Events following Reversal with Sugammadex or Neostigmine (the P-PERSoN Trial): Pilot Data Following Early Termination of a Prospective, Blinded, Randomised Trial.2022https://dx.doi.org/10.1155/2022/4659795
N.B. These documents automatically identified may not have been verified by the study sponsor.