Clinical trial NCT02825576: Prevention of Postoperative Events Following Reversal With Sugammadex or Neostigmine
Official title: Prevention of Postoperative Events Following Reversal With Sugammadex or Neostigmine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pulmonary Complications
Lead sponsor: Northern Sydney Anaesthesia Research Institute
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Northern Sydney and Central Coast Area Health Service
First posted: 2016-07-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if the use of sugammadex (compared with neostigmine) reduces the rate of postoperative pulmonary complications (PPCs).

Detailed description: This is a local, multi-centre, prospective, randomised, double blinded trial of 976 patients.

Objectives:

The primary objective is to determine if the use of sugammadex (compared with neostigmine) reduces the rate of postoperative pulmonary complications (PPCs). Secondary objectives are to determine if the use of sugammadex compared with traditional reversal agents improves patient quality of recovery, reduces the rate of postoperative nausea and vomiting and reduces the rate of airway complications in the Post Anaesthesia Care Unit (PACU).

Study procedures:

Following informed consent prior to surgery, patients will be randomised to two groups allocating drugs used for reversal of muscle relaxation;

1. 2mg/kg sugammadex
2. 50mcg/kg neostigmine with 10mcg/kg glycopyrrolate

Randomisation will be via computer generated numbers, which will be sealed in opaque, sequentially numbered envelopes.

Treating anaesthetist and staff assessing outcomes will be blinded to treatment.

Patients will have neuromuscular transmission (NMT) monitoring intraoperatively to ensure return of train-of-four count (TOFC) \>2 prior to reversal. Muscle relaxant will be limited to rocuronium or vecuronium, at the choice of the individual anaesthetist. As this study is planned to be a 'real world' trial, mode of anaesthesia, analgesia, postoperative nausea and vomiting (PONV) prophylaxis and time of reversal will be determined by the individual treating anaesthetist.

Postoperative outcome data will be collected in the recovery unit, on postoperative day 1 and 2 (if still an inpatient), at hospital discharge and via a 30 day post-operative phone call.

Statistical Analysis:

Conservatively estimating the baseline incidence of PPC at 7% baseline incidence and an equally conservative estimate that sugammadex can reduce this to 3% would produce a clinically relevant number needed to treat (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.

Groups will be analysed on an intention-to-treat basis

1. PPC rate, QoR-15 score and hospital stay will be assessed as continuous variables
2. Post operative Nausea and Vomiting (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.

Appropriate statistical tests to confirm test assumptions are met will be performed. In the case of non-parametric data, the appropriate test will be performed. Interim analysis is planned after 50% data completion.

Eligibility criteria: Inclusion Criteria:

* age \>18
* patients presenting for non-cardiac surgery
* planned operative time of over 1 hour
* plan to be intubated and to receive muscle relaxants for their surgery
* plan to stay at least one night in hospital

Exclusion Criteria:

* Previous recruitment to the trial
* Hypersensitivity to any of the study drugs
* Patient refusal
* Cognitive Impairment, or language proficiency leading to inability to complete QoR-15 questionnaire
* Body Mass Index (BMI) \>40
* Planned postoperative intubation and ventilation
* Liver failure with Child-Pugh class B/C
* Renal failure with either regular peritoneal or haemodialysis or serum creatinine \>140mcgmol/L
* Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study

Primary outcomes:
measure: Incidence of post operative pulmonary complications.
timeFrame: Up to day 2 post operatively.
Secondary outcomes:
measure: Quality of Recovery Score (QoR-15)
timeFrame: Day 1 and Day 30 post operatively
measure: Incidence of post operative nausea and vomiting.
timeFrame: Day of surgery.
measure: Incidence of airway events in the Post Anaesthesia Care Unit (PACU).
timeFrame: Day of surgery.
measure: Mortality
timeFrame: 30 day
measure: Hospital stay
timeFrame: 30 days
Other outcomes:
Locations:
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
Study officials:
affiliation: Northern Sydney Anaesthesia Research Institute
name: Ben L Olesnicky, BMBS BSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Olesnicky B, Doane M, Farrell C, Knoblanche G, Delaney A. 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. Anesthesiol Res Pract. 2022 Jul 8;2022:4659795. doi: 10.1155/2022/4659795. eCollection 2022.