PainPhase 4NCT01172197
Comparison of Levobupivacaine and Ropivacaine for Femoral Neural Block
A Phase 4 study testing Levobupivacaine and Ropivacaine in people with Pain and Arthroplasty, Replacement, Knee, run by NHS Tayside.
Trial summary
The anaesthetic management of patients undergoing total knee replacement is still not standardised. Epidural analgesia is common, but is associated with bilateral lower limb motor block and limited mobilisation. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pain, Arthroplasty, Replacement, Knee
- What is being tested?
- Levobupivacaine and Ropivacaine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- No sites listed yet
- Study dates
- Jan 2009to Oct 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients >18 years of age and non pregnant presenting for elective knee replacement
Who cannot join
- Signs of cardiac failure (3rd heart sound, lung crepitations)
- Type I and type II diabetes
- Abnormal cardiac arrhythmias
- Hypovolaemia
- Presence of seizures,
- Dementia,
Show all 12Show fewer
- Depression
- Encephalopathy,
- Terminal illness with a life expectancy < 3 months
- Age < 18 years
- Pregnant
- Coagulopathy
About this study
Official title: A Randomised Single Blind Study Comparing the Molar Median Effective Dose of Levobupivacaine and Molar Median Effective Dose of Ropivacaine When Administered as a Femoral Perineural Infusion for Pain Relief After Total Knee Replacement
The anaesthetic management of patients undergoing total knee replacement is still not standardised. Epidural analgesia is common, but is associated with bilateral lower limb motor block and limited mobilisation. Spinal anaesthesia with intrathecal morphine provides good pain relief, but only for 12 to 16 hours, and is often associated with nausea and vomiting. Combined single injection femoral / sciatic blocks give good pain relief, but for a variable length of time (between 12 and 24 hours).
In contrast, continuous femoral perineural infusion of local anaesthetic provides very good pain relief for several days. Pain relief is maintained by a constant infusion of local anaesthetic using an elastomeric ball. The investigators overriding aim is to develop a local anaesthetic regimen which offers complete pain relief for at least 48 hours, yet allows full mobilisation within 24 hours Given that ropivacaine may offer a more advantageous pharmacological profile (less lipid solubility) compared to levobupivacaine, the investigators feel it is pertinent to investigate the capacity of ropivacaine to prevent pain relief after surgery. Thus, the investigators aim in this study is to compare the median effective dose of levobupivacaine with the of ropivacaine for preventive pain relief after total knee replacement. Further, calculation of the equipotent median effective dose's of each local anaesthetic allied to objective measurement of quadriceps motor block using an electromyogram will allow us to determine the sensory - motor split of each local anaesthetic.
Read the detailed description
Primary objective The primary aim of this study is to measure the molar of levobupivacaine and the molar median effective dose of ropivacaine when administered as a femoral perineural infusion to prevent pain 30 hours after total knee replacement Secondary objectives
To assess the:
Degree of postoperative pain, need for rescue analgesia,side effect profile of both groups, self-efficacy, expectancy, quality of life / health economics Type of study: Prospective single blind randomised controlled trial Planned number of subjects: 48 Study duration: 24 months Randomisation procedures Following informed consent, participants will be randomised into two groups. All preparations for study will be coded so that participants have an equal chance of receiving one of the two local anesthetics. Randomisation will be carried out by computer program, and codes kept in pharmacy in a sealed envelope.
Protocol for patient management Preoperative - Anaesthetic room Antibiotics: augmentin 1.2 grams Sedation with Target Controlled Infusion of propofol at plasma level of 0.5 micrograms per millilitre (μg.ml-1) Spinal anaesthesia with 3.2 ml hypobaric "plain" bupivacaine 0.5% and intrathecal morphine 0.1 mg All regional nerve blocks performed under ultrasound control Femoral block: 15 ml 0.3% levobupivacaine or ropivacaineFemoral perineural catheter inserted by Anaesthetist 5cm in a cranial direction Sciatic block: single injection 12 ml 0.5% levobupivacaine or ropivacaine Obturator block: single injection 6 ml 0.5% levobupivacaine or ropivacaine
Postoperative 8 hour anaesthetic observation
Determine median effective dose of levobupivacaine and ropivacaine for anaesthesia 8 hours after insertion of spinal needle, resolution of spinal anaesthesia confirmed and verbal rating pain score of knee bending recorded. Clinical measurement and subsequent patient dosing is as follows:
- "Anaesthetic success": verbal rating pain score = 0: Next patient receives 10 microMolar (μM) less of levobupivacaine or 10μM ropivacaine.
- "Anaesthetic failure": verbal rating pain score ≥ 1. Resolved by rescue analgesia of 15ml, 150μM levobupivacaine (5.8ml, 0.75%) or 15ml, 150μM ropivacaine (6.2ml, 0.75%).Next patient receives 10μM more of levobupivacaine or 10μM ropivacaine.
- Technical failure: verbal rating pain score ≥ 1 Not resolved by rescue analgesia of 15ml, 150μM levobupivacaine (5.8ml, 0.75%) or 15ml, 150μM ropivacaine (6.2ml, 0.75%.Next patient receives same mass levobupivacaine or ropivacaine.
After the 8 hour assessment, all patients (excluding technical failures but including "anaesthetic failures") will start a femoral perineural infusion with levobupivacaine or ropivacaine at a rate of 10ml h-1 and concentration of 1(microMolar per millilitre) μM.ml-1 (400μM in 400ml elastomeric ball) for 48 hours.Patients classed as "technical failure" will have a femoral perineural catheter reinserted.
Postoperative 30 hour (±2hour) anaesthetic observation
The postoperative 30 hour anaesthetic observation will only be performed on the "anaesthetic successes" from the 8 hour observation. The median effective dose of levobupivacaine and ropivacaine for analgesia will be determined by choosing an end point of verbal rating pain score 0 at 30h after the start of spinal anaesthesia. Patients will divide into three groups:
- "Successful pain relief" verbal rating pain score = 0 Next patient receives 10μM less of levobupivacaine or 10μM ropivacaine.
- "Unsuccessful pain relief" verbal rating pain score ≥ 1 resolved by rescue analgesia of 15ml, 50μM levobupivacaine (5.8ml, 0.25% + saline) or 15ml, 50μM ropivacaine (7.7ml, 0.20% + saline).Next patient receives 10μM more of levobupivacaine or 10μM ropivacaine.
- Technical failure: verbal rating pain score ≥ 1. Not resolved by rescue analgesia of 15ml, 50μM levobupivacaine (5.8ml, 0.25% + saline) or ml, 50μM ropivacaine (7.7ml, 0.20% + saline).
Rescue analgesia Rescue will be standardised: 15ml, 50μM levobupivacaine (5.8ml, 0.25% + saline) or 15ml, 50μM ropivacaine (7.7ml, 0.20% + saline). The number of rescue administrations will be counted.
.
- Conditions
- Pain, Arthroplasty, Replacement, Knee
- Being tested
- Levobupivacaine, Ropivacaine
- Keywords
- local anesthetic, levobupivacaine, ropivacaine, femoral perineural block
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevobupivacaineDrug
Also called Chirocaine
Femoral bolus 150μM followed by femoral infusion 400μM
RopivacaineDrug
Also called Naropin
Bolus and infusion
| Study group | Role | What they receive |
|---|---|---|
| Ropivacaine | Active comparator | Local anaesthetic bolus and infusion Receives: Drug: Levobupivacaine |
| Levobupivacaine | Active comparator | Local anaesthetic bolus and infusion Receives: Drug: Ropivacaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain
Number achieving pain on movement of knee measured as 0 on a verbal pain rating scale at 30h after start of perineural infusion
Measured: 30 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2010 (estimated)
- Study startJan 2009
- Primary completionOct 2011
- Study completionOct 2011
Why it stopped: Terminated prior to its planned completion as anticipated by the protocol).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- NHS Tayside
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Graeme A McLeod, MD FRCA, Principal investigator, NHS Tayside
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01172197
- Sponsor's protocol ID
- 2008-002136-15
- Other IDs
- 2008-002136-15, 2008 AN02, 08/S1402/30, 24891/0009/001-0001, 2008
- Status last verified
- Apr 2018
- First submitted
- 28 Jul 2010
- Last updated
- 9 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Single Blind Study Comparing the Molar Median Effective Dose of Levobupivacaine and Molar Median Effective Dose of Ropivacaine When Administered as a Femoral Perineural Infusion for Pain Relief After Total Knee Replacement
- ClinicalTrials.gov ID
- NCT01172197
- Acronym / sponsor ID
- 2008-002136-15
- Conditions
- Pain, Arthroplasty, Replacement, Knee
- Keywords
- local anesthetic, levobupivacaine, ropivacaine, femoral perineural block
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated prior to its planned completion as anticipated by the protocol).
- Enrolment
- 14 participants (actual)
- Lead sponsor
- NHS TaysideOther government
- Study start
- Jan 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 29 Jul 2010 (estimated)
- Results
- Posted 9 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The anaesthetic management of patients undergoing total knee replacement is still not standardised. Epidural analgesia is common, but is associated with bilateral lower limb motor block and limited mobilisation. Spinal anaesthesia with intrathecal morphine provides good pain relief, but only for 12 to 16 hours, and is often associated with nausea and vomiting. Combined single injection femoral / sciatic blocks give good pain relief, but for a variable length of time (between 12 and 24 hours).
In contrast, continuous femoral perineural infusion of local anaesthetic provides very good pain relief for several days. Pain relief is maintained by a constant infusion of local anaesthetic using an elastomeric ball. The investigators overriding aim is to develop a local anaesthetic regimen which offers complete pain relief for at least 48 hours, yet allows full mobilisation within 24 hours Given that ropivacaine may offer a more advantageous pharmacological profile (less lipid solubility) compared to levobupivacaine, the investigators feel it is pertinent to investigate the capacity of ropivacaine to prevent pain relief after surgery. Thus, the investigators aim in this study is to compare the median effective dose of levobupivacaine with the of ropivacaine for preventive pain relief after total knee replacement. Further, calculation of the equipotent median effective dose's of each local anaesthetic allied to objective measurement of quadriceps motor block using an electromyogram will allow us to determine the sensory - motor split of each local anaesthetic.
Detailed description
Primary objective The primary aim of this study is to measure the molar of levobupivacaine and the molar median effective dose of ropivacaine when administered as a femoral perineural infusion to prevent pain 30 hours after total knee replacement Secondary objectives
To assess the:
Degree of postoperative pain, need for rescue analgesia,side effect profile of both groups, self-efficacy, expectancy, quality of life / health economics Type of study: Prospective single blind randomised controlled trial Planned number of subjects: 48 Study duration: 24 months Randomisation procedures Following informed consent, participants will be randomised into two groups. All preparations for study will be coded so that participants have an equal chance of receiving one of the two local anesthetics. Randomisation will be carried out by computer program, and codes kept in pharmacy in a sealed envelope.
Protocol for patient management Preoperative - Anaesthetic room Antibiotics: augmentin 1.2 grams Sedation with Target Controlled Infusion of propofol at plasma level of 0.5 micrograms per millilitre (μg.ml-1) Spinal anaesthesia with 3.2 ml hypobaric "plain" bupivacaine 0.5% and intrathecal morphine 0.1 mg All regional nerve blocks performed under ultrasound control Femoral block: 15 ml 0.3% levobupivacaine or ropivacaineFemoral perineural catheter inserted by Anaesthetist 5cm in a cranial direction Sciatic block: single injection 12 ml 0.5% levobupivacaine or ropivacaine Obturator block: single injection 6 ml 0.5% levobupivacaine or ropivacaine
Postoperative 8 hour anaesthetic observation
Determine median effective dose of levobupivacaine and ropivacaine for anaesthesia 8 hours after insertion of spinal needle, resolution of spinal anaesthesia confirmed and verbal rating pain score of knee bending recorded. Clinical measurement and subsequent patient dosing is as follows:
- "Anaesthetic success": verbal rating pain score = 0: Next patient receives 10 microMolar (μM) less of levobupivacaine or 10μM ropivacaine.
- "Anaesthetic failure": verbal rating pain score ≥ 1. Resolved by rescue analgesia of 15ml, 150μM levobupivacaine (5.8ml, 0.75%) or 15ml, 150μM ropivacaine (6.2ml, 0.75%).Next patient receives 10μM more of levobupivacaine or 10μM ropivacaine.
- Technical failure: verbal rating pain score ≥ 1 Not resolved by rescue analgesia of 15ml, 150μM levobupivacaine (5.8ml, 0.75%) or 15ml, 150μM ropivacaine (6.2ml, 0.75%.Next patient receives same mass levobupivacaine or ropivacaine.
After the 8 hour assessment, all patients (excluding technical failures but including "anaesthetic failures") will start a femoral perineural infusion with levobupivacaine or ropivacaine at a rate of 10ml h-1 and concentration of 1(microMolar per millilitre) μM.ml-1 (400μM in 400ml elastomeric ball) for 48 hours.Patients classed as "technical failure" will have a femoral perineural catheter reinserted.
Postoperative 30 hour (±2hour) anaesthetic observation
The postoperative 30 hour anaesthetic observation will only be performed on the "anaesthetic successes" from the 8 hour observation. The median effective dose of levobupivacaine and ropivacaine for analgesia will be determined by choosing an end point of verbal rating pain score 0 at 30h after the start of spinal anaesthesia. Patients will divide into three groups:
- "Successful pain relief" verbal rating pain score = 0 Next patient receives 10μM less of levobupivacaine or 10μM ropivacaine.
- "Unsuccessful pain relief" verbal rating pain score ≥ 1 resolved by rescue analgesia of 15ml, 50μM levobupivacaine (5.8ml, 0.25% + saline) or 15ml, 50μM ropivacaine (7.7ml, 0.20% + saline).Next patient receives 10μM more of levobupivacaine or 10μM ropivacaine.
- Technical failure: verbal rating pain score ≥ 1. Not resolved by rescue analgesia of 15ml, 50μM levobupivacaine (5.8ml, 0.25% + saline) or ml, 50μM ropivacaine (7.7ml, 0.20% + saline).
Rescue analgesia Rescue will be standardised: 15ml, 50μM levobupivacaine (5.8ml, 0.25% + saline) or 15ml, 50μM ropivacaine (7.7ml, 0.20% + saline). The number of rescue administrations will be counted.
.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ropivacaine | Active comparator | Drug: LevobupivacaineLocal anaesthetic bolus and infusion |
| Levobupivacaine | Active comparator | Drug: RopivacaineLocal anaesthetic bolus and infusion |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients >18 years of age and non pregnant presenting for elective knee replacement
Key exclusion criteria (12 listed)
- Signs of cardiac failure (3rd heart sound, lung crepitations)
- Type I and type II diabetes
- Abnormal cardiac arrhythmias
- Hypovolaemia
- Presence of seizures,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevobupivacaineAlso: ChirocaineFemoral bolus 150μM followed by femoral infusion 400μM | Drug | Ropivacaine |
| RopivacaineAlso: NaropinBolus and infusion | Drug | Levobupivacaine |
Primary outcome
Pain
Time frame: 30 hours
Number achieving pain on movement of knee measured as 0 on a verbal pain rating scale at 30h after start of perineural infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graeme A McLeod, MD FRCA principal investigator
NHS Tayside
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levobupivacaine and Ropivacaine in people with Pain and Arthroplasty, Replacement, Knee, run by NHS Tayside.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain (time frame: 30 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2018.