A Randomized Double Blind Controlled Trial Comparing Sugammadex and Neostigmine After Thoracic Anesthesia (DATA)

Decurarization After Thoracic Anesthesia - A Prospective Multicenter Double-blind Randomized Trial Comparing Sugammadex vs Neostigmine Reversal After Thoracic Anesthesia

At the end of anesthesia it's important to avoid residual neuromuscular block to ensure adequate respiratory function preventing postoperative pulmonary complications. This trial compares the neuromuscular block reversal with different drugs (sugammadex vs neostigmine) after thoracic anesthesia. The trial main objective is to demonstrate that sugammadex is faster than neostigmine to reach a Train-of-four-Ratio (TOF-ratio) of 0.9 after thoracic anesthesia, demonstrating that sugammadex allows a faster extubation. Other main purpose is to verify if there is a difference between sugammadex and neostigmine as regards adverse events after extubation and in the postoperative period (until the 30th day after surgery).

Note: TOF-ratio is defined as the ratio of the fourth muscular twitch/first twitch value during an accelerometric train-of-four stimulation.

Study Overview

• Status: Terminated
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: Sugammadex; Drug: Neostigmine

Detailed Description

Patients undergoing thoracic surgery will receive rocuronium as neuromuscular blocking agent. Anesthesia and neuromuscular blockade will be managed freely until the end of surgery. Then patients will be randomized to receive intravenous sugammadex or neostigmine/atropine as follows:

Sugammadex group:

• If Post tetanic count (PTC)=1-15: sugammadex 4 mg/kg
• If at least 1 twitch at the Train-of-four stimulation: sugammadex 2 mg/kg

Neostigmine group:

• If PTC=1-15: neostigmine 0.07 mg/kg + atropine 0.02 mg/kg
• If at least 1 twitch at the Train-of-four (TOF) stimulation: neostigmine 0.07 mg/kg + atropine 0.02 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Mi
    • Milan, Mi, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects scheduled for pulmonary resection, lobectomy, pneumonectomy, bullectomy, pleurodesis
• Age 18-70 years
• American Society of Anesthesiologists (ASA) class 1, 2, 3
• Body mass Index (BMI) = 18-30 kg/m2

Exclusion Criteria:

• Subjects scheduled for esophagectomy, thoracectomy, vascular resection
• Chronic Obstructive Pulmonary Disease (COPD) Gold class III e IV, respiratory infection, asthma
• Preoperative Forced Expiratory Volume in 1 second (FEV1) < 60% of predicted, Forced Expiratory Volume in 1 second/Forced Vital Capacity ratio (FEV1/FVC) <70%
• Preoperative Diffusion Lung capacity for carbon monoxide/Alveolar Volume ratio (DLCO/VA) < 60% of predicted
• Preoperative oxygen saturation (SpO2) <92% or Partial pressure of oxygen in arterial blood/Fraction of inspired oxygen (PaO2/FiO2) ratio <300
• Cardiovascular disease with Metabolic Equivalent of Tasks (METS) score less than 4
• Neuromuscular disorder
• Kidney failure defined as Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1,73 m2
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S Group; Sugammadex 2 or 4 mg/kg iv once at the end of surgery	Drug: Sugammadex; Sugammadex will be diluted in a saline water solution in a 10 mL syringe. Administration will be according to the neuromuscular blockade: If Post tetanic count = 1-15: 4 mg/kg; If at least 1 twitch at the Train-of-four stimulation: 2 mg/kg; Other Names: Bridion
Active Comparator: N Group; Neostigmine 0.05 or 0.07 mg/kg (+ atropine 0.02 mg/kg) iv once at the end of surgery	Drug: Neostigmine; Neostigmine will be diluted with atropine in a saline water solution in a 10 mL syringe. Administration will be according to the neuromuscular blockade: If Post tetanic count = 1-15: 0.07 mg/kg; If at least 1 twitch at the Train-of-four stimulation: 0.05 mg/kg Atropine will be administered at a 0.02 mg/kg dosage.; Other Names: Intrastigmina

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean time from reversal administration to Train-of-four-ratio (TOF-ratio) = 0.9	Time from reversal administration to at least 3 TOF-ratio value = or > 0.9	At the end of general anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean time from reversal administration to TOF-ratio = 1.0	Time from reversal administration to at least 3 TOF-ratio value = or > 1.0	At the end of general anesthesia
Mean time from reversal administration to extubation	Time from reversal administration to tracheal extubation	At the end of anesthesia
Muscular weakness incidence	Measured by the tongue depressor test	In the first 60 minutes after extubation
Hypoxemia or hypercapnia incidence	Hypoxemia defined as Partial pressure of oxygen in arterial blood/Fraction of inspired oxygen ratio (PaO2/FiO2) < 300. Hypercapnia defined as Partial pressure of carbon dioxide in arterial blood (PaCO2) > 45 mmHg.	In the first 60 minutes after extubation
Adverse events incidence	Incidence of nausea or vomit, abdominal pain, cardiac arrhythmias, hypotension coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology	In the first 60 minutes after extubation
Postoperative complications incidence	Incidence of medical and surgical complications coded according to the MedDRA terminology	Participants will be followed for the duration of hospital stay, an expected average of 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean time of hospital discharge	Time from intervention date to the hospital discharge	Participants will be followed for the duration of hospital stay, an expected average of 7 days
Postoperative complications incidence	Incidence of medical and surgical complications coded according to the MedDRA terminology	At 30 days after surgery

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Federico Piccioni, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: September 24, 2014
• First Submitted That Met QC Criteria: October 1, 2014
• First Posted (Estimate): October 3, 2014

Study Record Updates

• Last Update Posted (Actual): June 16, 2021
• Last Update Submitted That Met QC Criteria: June 12, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Thoracic surgery; Neuromuscular blockade
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Parasympathomimetics; Neostigmine
• Other Study ID Numbers: INT-91/14; 2014-002021-35 (EudraCT Number)