Chloroprocaine 2% vs Ropivacaine 0.75% in Ultrasound-guided Axillary Nerve Block

A Prospective, Randomised, Non-inferiority Study of Chloroprocaine 2% and the Active Control Ropivacaine 0.75% (AstraZeneca) in Ultrasound-guided Axillary Nerve Block for Short-duration Distal Upper Limb Surgery

The Study evaluate the non-inferiority of Test product (Chloroprocaine 2%) versus Reference product (Ropivacaine 0.75%) in terms of proportion of subjects with a successful block for distal upper limb surgeries Successful block: anaesthesia adequate for the surgery without any supplementation in the first 45 min.

Study Overview

• Status: Completed
• Conditions: Axillary Nerve Block
• Intervention / Treatment: Drug: Chloroprocaine HCl 2%; Drug: Ropivacaine 0.75%

Detailed Description

This Study evaluate the non-inferiority of Test product (Chloroprocaine 2%) versus Reference product (Ropivacaine 0.75%) in terms of proportion of subjects with a successful block for distal upper limb surgeries, without any supplementation in the first 45 min (see definitions below), calculated from the time of readiness for surgery (complete sensory block). Successful block: anaesthesia adequate for the surgery (complete sensory block), without any supplementation in the first 45 min (even if surgery lasts for > 45 min), calculated from the time of readiness for surgery (complete sensory block). Supplementation: i.v. premedication or general anaesthesia or pre- or intra-operative systemic analgesia or additional local anaesthetic infiltration

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Lugano
    • Gravesano, Lugano, Switzerland, CH-6929
      • Claudio Camponovo

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:

1. Sex and surgery: male and female patients scheduled for short duration (< 60 min) distal upper limb surgery under axillary nerve block anaesthesia
2. Age: ≥ 18 years old
3. Body Mass Index (BMI): 18 - 32 kg/m2 inclusive
4. ASA physical status: I-III
5. Informed consent: signed written informed consent before inclusion in the study
6. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study

Exclusion Criteria:

1. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study. Contraindications to peripheral nerve block anaesthesia. History of neuromuscular diseases to the upper extremities
2. Axillary status: Axillary local infections, surgical scarring and pathological lymph node enlargement
3. ASA physical status: IV-V
4. Further anaesthesia: Patients anticipated to be requiring further anaesthesia (general or local anaesthesia)
5. Chronic pain syndromes: Patients with chronic pain syndromes (taking opioids, antidepressants, anticonvulsant agents)
6. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients; ascertained or presumptive hypersensitivity to the amide and ester-type anaesthetics
7. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study; ascertained psychiatric diseases, sepsis, blood coagulation disorders, insulin dependent diabetes mellitus, terminal kidney failure
8. Medications: Medication known to interfere with the extent of regional blocks (see chloroprocaine and ropivacaine SmPCs) for 2 weeks before the start of the study. Hormonal contraceptives for females will be allowed
9. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study, calculated from the first day of the month following the last visit of the previous study
10. Drug, alcohol: history of drug or alcohol abuse
11. Pregnancy: missing or positive pregnancy test at screening, pregnant or lactating 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: Chloroprocaine HCl 2% (20 mg/mL); Chloroprocaine 2 % Solution for injection, single administration by axillary nerve route 20 mL	Drug: Chloroprocaine HCl 2%; Single Administration (20mL) by Axillary Nerve Route; Other Names: Ampres
Active Comparator: Ropivacaine 0.75% (7.5 mg/mL); Ropivacaine 0.75% Solution for injection, single administration by axillary nerve route 20 mL	Drug: Ropivacaine 0.75%; Single Administration (20mL) by Axillary Nerve Route; Other Names: Naropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Successful Block for Distal Upper Limb Surgeries	Percentage of patients with a successful block for distal upper limb surgeries, without any supplementation in the first 45 min, calculated from the time of readiness for surgery (complete sensory block).	45 min from the time of readiness of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of Sensory Block (Corresponding to Readiness for Surgery)	Time period from completion of the final perineural injection (time 0 h) to achievement of sensory block in the 4 nerve territories	Up to 1 h after last perineural injection
Time to Onset of Motor Block	Time period from completion of the final perineural injection (time 0 h) to achievement of motor block	Up to 1 h after last perineural injection
Time to Regression of Sensory Block	Will be deemed to have occurred when cold sensation and sensitive perception have returned (if assessable) in any nerve territory	Up to 12 hrs after surgery
Time to Regression of Motor Block	Will be deemed to have occurred when motor score is ≥ 3 (Modified Bromage scale) in any nerve territory (Modified Bromage scale: 0-No movement in relevant muscle group,1-Flicker of movement in relevant muscle group,2-Ability to move relevant muscle group against gravity but inability to move against resistance,3-Reduced power but ability to move muscle group against resistance,4-Full power in relevant muscle group)	Up to 12 hrs after surgery
Partecipants Received Rescue Anaesthesia or Rescue Analgesia	partecipants received rescue anaesthesia or rescue analgesia from completion of the final perineural injection (time 0 hour) to administration of first rescue anaesthesia or analgesia (supplementation)	45 min from the time of readiness of surgery
Number of Subjects Who Received Post-operative Analgesia	Number of subjects who received the first post-operative analgesia	From surgery day to 24 hrs post surgery
Time to Eligibility for Home Discharge	Time from completion of the final perineural injection (time 0 h) to the time when the criteria for discharge are met, even if, according to the hospital procedures, the patient is discharged from the hospital at a later time	from surgery day to 24h post surgery
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Number of Participants with Treatment-emergent Adverse Events (TEAEs) occurring or worsening after the first dose of IMP	from surgery day to day 6 +/- 1 after surgery
Neurological Symptoms	Number of patients with Neurological Symptoms (e.g. paraesthesia, motor function problems and pain at the injection site)	from surgery day to day 6 +/- 1 after surgery
Heart Rate	The following normal ranges Heart Rate parameters will be used: 50-90 beats/min	from surgery day to 24 hrs post surgery
Blood Pressure	The following normal ranges Systolic and Diastolic Blood Pressure parameters will be used: Systolic Blood Pressure: 100-139 mmHg Diastolic Blood Pressure: 50-89 mmHg	from surgery day to 24 hrs post surgery
SpO2	The following normal ranges SpO2 parameters will be used: Peripheral Oxygen Saturation: ≥ 95%	from surgery day to 24 hrs post surgery
Number of Participants With Normal Electrocardiogram (ECG) Parameters	Number of Participants with Normal Electrocardiogram (ECG) Parameters. The following normal ranges ECG parameters will be used: Heart Rate: 50-90 beats/min PR Interval: 100-220 msec QRS Duration: ≤ 120 msec QT Interval: ≤ 500 msec	from surgery day to 24 hrs post surgery

Collaborators and Investigators

• Sponsor: Sintetica SA
• Collaborators: Cross S.A.
• Investigators: Principal Investigator: Claudio Camponovo, MD, Department of Anaesthesiology,Clinica Ars Medica,Via Cantonale, CH-6929 Gravesano, Switzerland; Principal Investigator: Oliver Kimberger, Prof, Department of General Anesthesia and Intensive Care Medicine, Spitalgasse 23, 1090 Vienna, Austria; Principal Investigator: Andrea Saporito, MD, Department of Anaesthesiology, Ospedale Regionale di Bellinzona, CH-6500 Bellinzona, Switzerland

Publications and helpful links

General Publications

• Sulyok I, Camponovo C, Zotti O, Haslik W, Kostenberger M, Likar R, Leuratti C, Donati E, Kimberger O. A randomised, non-inferiority study of chloroprocaine 2% and ropivacaine 0.75% in ultrasound-guided axillary block. Sci Rep. 2021 May 11;11(1):10035. doi: 10.1038/s41598-021-89483-y.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: February 20, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 11, 2015

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: June 24, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Ropivacaine; Chloroprocaine
• Other Study ID Numbers: CHL.2/01-2014/M