Prevention of Postoperative Events Following Reversal With Sugammadex or Neostigmine

Pulmonary Complications Clinical Trial

— P-PERSON  

Official title:

Prevention of Postoperative Events Following Reversal With Sugammadex or Neostigmine

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02825576
• Other study ID #: MSD-IIS-54809
• Status: Terminated
• Phase: Phase 4
• Start date: December 3, 2018
• Est. completion date: January 1, 2021

Study information

• Verified date: March 2023
• Source: Northern Sydney Anaesthesia Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: January 1, 2021
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pulmonary Complications

Intervention

Drug:
• Sugammadex
Sugammadex 2mg/kg given for reversal agent
• Neostigmine/Glycopyrrolate
Neostigmine 50 mcg/kg plus Glycopyrrolate 10 mcg/kg given for reversal agent

Locations

Country	Name	City	State
Australia	Royal North Shore Hospital	St Leonards	New South Wales

Sponsors (3)

Lead Sponsor	Collaborator
Northern Sydney Anaesthesia Research Institute	Merck Sharp & Dohme LLC, Northern Sydney and Central Coast Area Health Service

Country where clinical trial is conducted

Australia, 

References & Publications (1)

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. Anesth — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of post operative pulmonary complications.	Incidence of Postoperative pulmonary complications as defined by The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) group.	Up to day 2 post operatively.
Secondary	Quality of Recovery Score (QoR-15)	A 15- item patient-rated post operative questionnaire designed to assess the early postoperative health status of patients after anesthesia and surgery.	Day 1 and Day 30 post operatively
Secondary	Incidence of post operative nausea and vomiting.	Post Operative Nausea and Vomiting (PONV) Score: - no PONV; - PONV responsive to antiemetics; - PONV unresponsive to antiemetics	Day of surgery.
Secondary	Incidence of airway events in the Post Anaesthesia Care Unit (PACU).	Proportion of patient that exhibit one or more of the following PACU Events (recorded by recovery room nursing staff); Any desaturation to oxygen saturation by pulse oximetry (SpO2) <90%; Need for manual airway support; Need for oropharyngeal or nasopharyngeal airway; Need for reintubation in PACU; Need for anaesthetist to review the patient; Unplanned Intensive Care Unit (ICU) admission	Day of surgery.
Secondary	Mortality	Death of patient within time frame.	30 day
Secondary	Hospital stay	Duration of hospital stay	30 days