Prevention of Postoperative Events Following Reversal With Sugammadex or Neostigmine (P-PERSON)

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

Study Overview

• Status: Terminated
• Conditions: Pulmonary Complications
• Intervention / Treatment: Drug: Sugammadex; Drug: Neostigmine/Glycopyrrolate

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ben L Olesnicky, BMBS Bsc; Phone Number: +61 2 9463 2488; Email: bolesnicky@hotmail.com

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sugammadex group; Sugammadex 2mg/kg intravenously at completion of surgery.	Drug: Sugammadex; Sugammadex 2mg/kg given for reversal agent; Other Names: Bridion
Active Comparator: Neostigmine/Glycopyrrolate group; Neostigmine 50mcg/kg plus Glycopyrrolate 10mcg/kg intravenously at completion of surgery.	Drug: Neostigmine/Glycopyrrolate; Neostigmine 50 mcg/kg plus Glycopyrrolate 10 mcg/kg given for reversal agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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.
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.
Mortality	Death of patient within time frame.	30 day
Hospital stay	Duration of hospital stay	30 days

Collaborators and Investigators

• Sponsor: Northern Sydney Anaesthesia Research Institute
• Collaborators: Merck Sharp & Dohme LLC; Northern Sydney and Central Coast Area Health Service
• Investigators: Principal Investigator: Ben L Olesnicky, BMBS BSc, Northern Sydney Anaesthesia Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: June 21, 2016
• First Submitted That Met QC Criteria: July 4, 2016
• First Posted (Estimate): July 7, 2016

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Adjuvants, Anesthesia; Cholinesterase Inhibitors; Parasympathomimetics; Glycopyrrolate; Neostigmine
• Other Study ID Numbers: MSD-IIS-54809

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No