PainPhase 4NCT01114997
Effect of Lidocaine and Esmolol to Improve the Quality of Recovery
A Phase 4 study testing Lidocaine, Esmolol and Lidocaine + Esmolol (Combo) in people with Pain and Constipation, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
The purpose of this prospective, randomized, double-blinded, active-controlled study is: To assess the effectiveness of systemic administration of lidocaine and esmolol in combination (vs. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pain, Constipation, Nausea
- What is being tested?
- Lidocaine, Esmolol and Lidocaine + Esmolol (Combo)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Jun 2015
- 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
- Patients scheduled to undergo abdominal surgical procedures
- Willingness and ability to sign an informed consent document
- No allergies to anesthetic or analgesic medications
- 18 - 80 years of age
- American Society of Anesthesiologists (ASA) physical status classification: Class I - III adults of either sex
- Women of childbearing potential must be currently practicing an acceptable form of birth control, and have a negative urine or blood pregnancy test
- Patients with systolic blood pressure greater than 80 and less than 150 at baseline, diastolic blood pressure less than 100 at baseline.
Who cannot join
- Inability to comprehend the pain assessment tools.
- Patients with known allergy, hypersensitivity or contraindications to anesthetic or analgesic medications
- Patients with clinically-significant medical conditions, such as brain, heart, kidney, endocrine, or liver diseases,
- Peptic ulcer disease or bleeding disorders
- Patients with history of hepatic, renal, cardiac failure, organ transplant, or diabetes
- Patients with reactive airway disease (asthma)
Show all 12Show fewer
- Patients with seizures
- Chronic use of ß-blocker or calcium channel blocker
- Morbid obesity (body mass index >40)
- Pregnant or lactating women
- Subjects with a history of alcohol or drug abuse within the past 3 months
- Any other conditions or use of any medication which may interfere with the conduct of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: Effect of Lidocaine and Esmolol Alone or in Combination to Improve the Quality of Recovery, Maintaining Hemodynamic Stability During Abdominal Surgery
The purpose of this prospective, randomized, double-blinded, active-controlled study is:
To assess the effectiveness of systemic administration of lidocaine and esmolol in combination (vs. either drug alone) will result in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less pain and postoperative constipation, nausea and vomiting, faster return of bowel function, resumption of normal activities of daily living), leading to a shorten length of hospital stay, maintaining hemodynamic stability during general anesthesia, when administered as intravenous adjuvants
Read the detailed description
Finding the optimal combination of anesthetic adjuvant drugs for maintaining hemodynamic stability during surgery is a challenge (1-3). Traditionally, potent opioid analgesics like fentanyl and its newer analogs have been used for this purpose. However, use of opioid compounds is associated with well-known side effects (e.g., ventilatory depression, postoperative nausea and vomiting, constipation, ileus, bladder dysfunction, urinary retention, pruritus, drowsiness and sedation). All of these common side effects interfere with the early recovery process and contribute to a delayed resumption of normal activities (4, 5). Increasingly, non-opioid analgesics (e.g. β-blockers and local anesthetics) are being utilized as adjuvant drugs during surgery for treatment of acute hyperdynamic responses (increased catecholamine release) during surgery, as well as, facilitation of the recovery process after surgery because of their anesthetic and analgesic-sparing effects. The β-blocking drugs, esmolol and labetalol have been used as an alternative to short-acting opioid analgesics for controlling the transient, acute autonomic responses during surgery (5-8), They have been shown to reduce the anesthetic requirement during intravenous (propofol) or volatile-based anesthesia (6,7,10-13) and to decrease opioid consumption intraoperatively and in the PACU (8). They may also improve hemodynamic stability during induction and emergence from anesthesia in the perioperative and early postoperative period and facilitate the resumption of normal activities after major surgical procedures. The anesthetic and analgesic-sparing effects of β -blockers also lead to a faster emergence from anesthesia and reduce postoperative opioid side effects (e.g., PONV) (14-18). Perioperative intravenous esmolol has shown improvement in perioperative outcomes, decreases acute hemodynamic responses, reduces anesthetics and opioids use during anesthesia, facilitates a faster emergence from anesthesia, reduces intraoperative and postoperative opioid requirements, reduces side effects as such as pruritus, constipation, ileus, nausea and vomiting (PONV) and thereby shortens the hospital stay. (3, 7, 13, 18)
Local anesthetics like lidocaine possess analgesic, antihyperalgesic and anti-inflammatory properties. Perioperative intravenous lidocaine has shown improvement in perioperative outcomes in patients undergoing abdominal surgery to decrease intraoperative requirement of Inhalants/Intravenous agents, opioid consumption, postoperative pain, fatigue, nausea and vomiting scores, maintain hemodynamic stability, facilitate a more rapid recovery of gastrointestinal function, improve postoperative recovery, fast resumption of normal activities of daily living and shorten length of hospital stay, when administered as an adjuvant during surgery.(19,23-29,33)
Theoretically, it would be extremely beneficial to administer an adjuvant (to patients undergoing abdominal surgery) that is capable of effectively controlling autonomic responses during surgery, while providing a faster recovery with fewer side effects. Preliminary data suggests that the perioperative effects of systemic administration of lidocaine and esmolol is most effective in facilitating bowel recovery, decreasing opioid consumption in the intra/postoperative period, and shorten length of hospital stay with early recovery. Therefore, we designed this prospective, randomized, double-blinded, active-controlled study to test the hypothesis that systemic administration of lidocaine and esmolol in combination (vs. either drug alone) for maintenance of hemodynamic stability during surgery will result in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less pain and postoperative nausea and vomiting, and faster return of bowel function and resumption of normal activities of daily living); leading to a shorten length of hospital stay.
- Conditions
- Pain, Constipation, Nausea, Vomiting
- Being tested
- Lidocaine, Esmolol, Lidocaine + Esmolol (Combo)
- Keywords
- Lidocaine Infusion, Esmolol Infusion, Anesthetic adjuvant, Abdominal surgery, Pain management, Hemodynamic stability, Perioperative outcomes
- Medical subject headings
- Pain, Constipation, Nausea, Vomiting, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LidocaineDrug
Pre-Induction: Lidocaine Loading: 1 mg/kg After Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h)
EsmololDrug
Esmolol Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Esmolol Post Induction: Infusion dose 7.5 - 15 mcg /kg/min
Lidocaine + Esmolol (Combo)Drug
Pre-induction: Lidocaine Loading dose(1 mg/kg) + Esmolol Loading dose(750 mcg/Kg)
Maintenance Infusion rate after Induction:
Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min)
| Study group | Role | What they receive |
|---|---|---|
| Lidocaine | Active comparator | Pre-Induction: Lidocaine Loading: 1 mg/kg Post- Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h) Receives: Drug: Lidocaine |
| Esmolol | Active comparator | Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min Receives: Drug: Esmolol |
| Lidocaine + Esmolol (Combo) | Experimental | Performed with the administration of both drugs.
Pre-induction:
Lidocaine Loading dose(1 mg/kg)+Esmolol Loading dose(750 mcg/Kg)
Post-induction:
Infusion rate: Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min) Receives: Drug: Lidocaine + Esmolol (Combo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post Operative Pain
Outcome had a duration of one day at post-anesthesia care unit (PACU) Postoperative pain measured using a Verbal Rating Scale (VRS) Postoperative pain VRS scores: 0 = none pain to 10 = intolerable pain.
Measured: 1 day
Number of Participants With Post Operative Pain One Month After Surgery
Highest Post Operative pain one month after surgery, using a verbal rating score from 0 (no pain) to 10 (highest level of pain).
Patient received a post-operative follow-up call one month after surgery.
Measured: 1 month
Secondary outcomes (5)
Opioid Consumption Obtained From the Recorded Data
Postoperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts)
Measured: 1 day
Number of Participants With Postoperative Nausea One Day After Surgery
Postoperative nausea using a Verbal Rating Scale Outcomes measured at the first day after surgery
Measured: 1day
Return to Normal Activities of Daily Living Using Follow up Questionnaires
Description: return to normal activities of daily living(including dietary intake, bowel and bladder function, physical activities)
Measured: 1 month
Patient Satisfaction
Patient satisfaction using a verbal rating scale from 0 to 10 0= Not satisfied 10= Excellent
Measured: 1 month
Post-anesthesia Care Unit (PACU) Stay
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2010 (estimated)
- Study startApr 2010
- Primary completionJun 2015
- Study completionJun 2015
Why it stopped: The early report didn't show any benefit.
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.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roya Yumul, M.D.,PhD., Cedars-Sinai Medical Center
- Investigators
- Roya Yumul, MD, PhD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01114997
- Sponsor's protocol ID
- Pro00020608
- Status last verified
- Sep 2016
- First submitted
- 23 Apr 2010
- Last updated
- 3 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Lidocaine and Esmolol Alone or in Combination to Improve the Quality of Recovery, Maintaining Hemodynamic Stability During Abdominal Surgery
- ClinicalTrials.gov ID
- NCT01114997
- Acronym / sponsor ID
- Pro00020608
- Conditions
- Pain, Constipation, Nausea, Vomiting
- Keywords
- Lidocaine Infusion, Esmolol Infusion, Anesthetic adjuvant, Abdominal surgery, Pain management, Hemodynamic stability, Perioperative outcomes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The early report didn't show any benefit.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 3 May 2010 (estimated)
- Results
- Posted 23 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this prospective, randomized, double-blinded, active-controlled study is:
To assess the effectiveness of systemic administration of lidocaine and esmolol in combination (vs. either drug alone) will result in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less pain and postoperative constipation, nausea and vomiting, faster return of bowel function, resumption of normal activities of daily living), leading to a shorten length of hospital stay, maintaining hemodynamic stability during general anesthesia, when administered as intravenous adjuvants
Detailed description
Finding the optimal combination of anesthetic adjuvant drugs for maintaining hemodynamic stability during surgery is a challenge (1-3). Traditionally, potent opioid analgesics like fentanyl and its newer analogs have been used for this purpose. However, use of opioid compounds is associated with well-known side effects (e.g., ventilatory depression, postoperative nausea and vomiting, constipation, ileus, bladder dysfunction, urinary retention, pruritus, drowsiness and sedation). All of these common side effects interfere with the early recovery process and contribute to a delayed resumption of normal activities (4, 5). Increasingly, non-opioid analgesics (e.g. β-blockers and local anesthetics) are being utilized as adjuvant drugs during surgery for treatment of acute hyperdynamic responses (increased catecholamine release) during surgery, as well as, facilitation of the recovery process after surgery because of their anesthetic and analgesic-sparing effects. The β-blocking drugs, esmolol and labetalol have been used as an alternative to short-acting opioid analgesics for controlling the transient, acute autonomic responses during surgery (5-8), They have been shown to reduce the anesthetic requirement during intravenous (propofol) or volatile-based anesthesia (6,7,10-13) and to decrease opioid consumption intraoperatively and in the PACU (8). They may also improve hemodynamic stability during induction and emergence from anesthesia in the perioperative and early postoperative period and facilitate the resumption of normal activities after major surgical procedures. The anesthetic and analgesic-sparing effects of β -blockers also lead to a faster emergence from anesthesia and reduce postoperative opioid side effects (e.g., PONV) (14-18). Perioperative intravenous esmolol has shown improvement in perioperative outcomes, decreases acute hemodynamic responses, reduces anesthetics and opioids use during anesthesia, facilitates a faster emergence from anesthesia, reduces intraoperative and postoperative opioid requirements, reduces side effects as such as pruritus, constipation, ileus, nausea and vomiting (PONV) and thereby shortens the hospital stay. (3, 7, 13, 18)
Local anesthetics like lidocaine possess analgesic, antihyperalgesic and anti-inflammatory properties. Perioperative intravenous lidocaine has shown improvement in perioperative outcomes in patients undergoing abdominal surgery to decrease intraoperative requirement of Inhalants/Intravenous agents, opioid consumption, postoperative pain, fatigue, nausea and vomiting scores, maintain hemodynamic stability, facilitate a more rapid recovery of gastrointestinal function, improve postoperative recovery, fast resumption of normal activities of daily living and shorten length of hospital stay, when administered as an adjuvant during surgery.(19,23-29,33)
Theoretically, it would be extremely beneficial to administer an adjuvant (to patients undergoing abdominal surgery) that is capable of effectively controlling autonomic responses during surgery, while providing a faster recovery with fewer side effects. Preliminary data suggests that the perioperative effects of systemic administration of lidocaine and esmolol is most effective in facilitating bowel recovery, decreasing opioid consumption in the intra/postoperative period, and shorten length of hospital stay with early recovery. Therefore, we designed this prospective, randomized, double-blinded, active-controlled study to test the hypothesis that systemic administration of lidocaine and esmolol in combination (vs. either drug alone) for maintenance of hemodynamic stability during surgery will result in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less pain and postoperative nausea and vomiting, and faster return of bowel function and resumption of normal activities of daily living); leading to a shorten length of hospital stay.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lidocaine | Active comparator | Drug: LidocainePre-Induction: Lidocaine Loading: 1 mg/kg Post- Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h) |
| Esmolol | Active comparator | Drug: EsmololPre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Post-Induction: Infusion dose 7.5 - 15 mcg /kg/min |
| Lidocaine + Esmolol (Combo) | Experimental | Drug: Lidocaine + Esmolol (Combo)Performed with the administration of both drugs. Pre-induction: Lidocaine Loading dose(1 mg/kg)+Esmolol Loading dose(750 mcg/Kg) Post-induction: Infusion rate: Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients scheduled to undergo abdominal surgical procedures
- Willingness and ability to sign an informed consent document
- No allergies to anesthetic or analgesic medications
- 18 - 80 years of age
- American Society of Anesthesiologists (ASA) physical status classification: Class I - III adults of either sex
Key exclusion criteria (12 listed)
- Inability to comprehend the pain assessment tools.
- Patients with known allergy, hypersensitivity or contraindications to anesthetic or analgesic medications
- Patients with clinically-significant medical conditions, such as brain, heart, kidney, endocrine, or liver diseases,
- Peptic ulcer disease or bleeding disorders
- Patients with history of hepatic, renal, cardiac failure, organ transplant, or diabetes
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 |
|---|---|---|
| LidocainePre-Induction: Lidocaine Loading: 1 mg/kg After Induction:Lidocaine Infusion: 12.5-25 mcg/kg/min 0.75-1.5 mg/kg/h) | Drug | Lidocaine |
| EsmololEsmolol Pre-Induction: Loading dose 750 mcg/Kg (0.75 mg/kg) Esmolol Post Induction: Infusion dose 7.5 - 15 mcg /kg/min | Drug | Esmolol |
| Lidocaine + Esmolol (Combo)Pre-induction: Lidocaine Loading dose(1 mg/kg) + Esmolol Loading dose(750 mcg/Kg) Maintenance Infusion rate after Induction: Lidocaine(12.5-25 mcg/kg/min) + Esmolol(7.5-15 mcg/kg/min) | Drug | Lidocaine + Esmolol (Combo) |
Primary outcome
Post Operative Pain
Time frame: 1 day
Outcome had a duration of one day at post-anesthesia care unit (PACU) Postoperative pain measured using a Verbal Rating Scale (VRS) Postoperative pain VRS scores: 0 = none pain to 10 = intolerable pain.
Number of Participants With Post Operative Pain One Month After Surgery
Time frame: 1 month
Highest Post Operative pain one month after surgery, using a verbal rating score from 0 (no pain) to 10 (highest level of pain). Patient received a post-operative follow-up call one month after surgery.
5 secondary outcomes
Opioid Consumption Obtained From the Recorded Data
Time frame: 1 day
Number of Participants With Postoperative Nausea One Day After Surgery
Time frame: 1day
Return to Normal Activities of Daily Living Using Follow up Questionnaires
Time frame: 1 month
Patient Satisfaction
Time frame: 1 month
Post-anesthesia Care Unit (PACU) Stay
Time frame: 1 day
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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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.
Roya Yumul, MD, PhD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lidocaine, Esmolol and Lidocaine + Esmolol (Combo) in people with Pain and Constipation, run by Cedars-Sinai Medical Center at 1 site in United States.
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 7 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 3 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 23 Jun 2016). 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?
Post Operative Pain (time frame: 1 day). The study lists 2 primary outcomes in all. 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 3 Nov 2016.