Assessment of Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion (LEVOROPI)

Prospective Randomized Double-blinded Study of Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion

The aim of the study is the assessment of the systemic absorption of local anesthetics during continuous epidural infusion for postoperative pain control.

Study Overview

• Status: Completed
• Conditions: Surgery; Anesthesia
• Intervention / Treatment: Drug: local anesthetic

Detailed Description

In literature the systemic toxicity of bupivacaine is widely demonstrated, like the minor toxicity of levobupivacaine and ropivacaine at the same anesthetic potency. The are actually no studies in humans confronting levobupivacaine and ropivacaine under the aspect of efficacy and toxicity.The aim of the study is the assessment of the systemic absorption of local anesthetics during continuous epidural infusion for postoperative pain control.

Primary outcome:

Assessment of the plasmatic equimolar concentrations of levobupivacaine and ropivacaine during continuous epidural infusion

Secondary outcome:

Assessment of the safety level of the local anesthetic (major difference between haematic concentration of the local anesthetic and neuro-cardiotoxic dose).

Difference of the analgesic efficacy between levobupivacaine and ropivacaine. Differences in collateral effects due to the local anesthetic: hypotension and sensitive block.

Prospective randomized double-blinded clinical trial

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Monza, Italy, 20052
    • Unità operativa di Anestesia e Rianimazione - Azienda Ospedaliera San Gerardo
  • Lombardia
    • Pavia, Lombardia, Italy, 27100
      • IRCCS Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I or ASA II
• Scheduled for major surgery
• written informed consent

Exclusion Criteria:

• ASA III, IV
• Emergency surgery
• Recovery in intensive care unit after surgery
• habitual opioid consumption
• cognitive or mental alterations
• coagulopathy
• piastrinemia < 100.000/mm3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: levobupivacaine	Drug: local anesthetic; postoperative 48h epidural continuous infusion,; ropivacaine 0,2% (250ml)+ sufentanil 0,75mcg/ml; levobupivacaine 0,125% (250ml)+ sufentanil 0,75mcg/ml; Other Names: Naropina; Chriocaina
Other: ropivacaine	Drug: local anesthetic; postoperative 48h epidural continuous infusion,; ropivacaine 0,2% (250ml)+ sufentanil 0,75mcg/ml; levobupivacaine 0,125% (250ml)+ sufentanil 0,75mcg/ml; Other Names: Naropina; Chriocaina

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of the local anesthetics in study	Assessment of the equivalence of the systemic exposition of levobupivacaine and ropivacaine during 48h continuous epidural infusion with in a range of 15%.Blood samples (8) will be taken for farmacological assessment of local anesthetic plasma concentrations at time (hours) 0,+3h,+6h,+12h,+24h,+48h,+54h,+60h	during 60h after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the pharmacological profile of the local anesthetics in study	Assessment of the therapeutic index (plasma concentration of the local anesthetics in study compared to those described in literature to be related to toxic effects).	during 60h after surgery
Difference between the to groups (at least 25%) in terms of pain control (1 episode of VAS>4)		Pain control (VAS, VASm, rescue dose) during the 72 h postsurgery
Difference at least 20% in presentation of collateral effects between the two groups		Continuous assessment during the 72 h post-surgery

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Matteo
• Investigators: Principal Investigator: Massimo Allegri, MD, IRCCS Policlinico San Matteo

Publications and helpful links

General Publications

• Perotti L, Cusato M, Ingelmo P, Niebel TL, Somaini M, Riva F, Tinelli C, De Andres J, Fanelli G, Braschi A, Regazzi M, Allegri M. A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial. Anesth Analg. 2015 Aug;121(2):348-56. doi: 10.1213/ANE.0000000000000775.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: October 26, 2010
• First Posted (Estimate): October 27, 2010

Study Record Updates

• Last Update Posted (Estimate): January 20, 2012
• Last Update Submitted That Met QC Criteria: January 19, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; epidural; local anesthetic; plasmatic concentration; epidural continuous infusion
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local
• Other Study ID Numbers: 2010-019393-32