AnesthesiaPhase 3NCT00675792
Comparison of Sugammadex Administered at 1-2 Post Tetanic Counts (PTCs) or Better With Neostigmine Administered as Per Standard of Care to Reverse Rocuronium-Induced Neuromuscular Blockade in Adults Undergoing Elective Open Abdominal Procedure (19.4.334) (P05774)
A Phase 3 study testing Sugammadex, Neostigmine and Rocuronium in people with Anesthesia, run by Merck Sharp & Dohme LLC.
Trial summary
The primary purpose of this study is to compare the incidence of residual neuromuscular blockade at the time of tracheal extubation after reversal of rocuronium bromide-induced neuromuscular blockade by 4 mg/kg sugammadex with that of 50 µg/kg neostigmine. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Anesthesia
- What is being tested?
- Sugammadex, Neostigmine and Rocuronium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- May 2008to Sep 2008
- Phase
- Phase 3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or females who are >= 18 and <= 65 years of age
- classified by the American Society of Anesthesiologists (ASA) as Class 1 or 2 or 3;
- Body Mass Index (BMI) of <35 kg/m^2;
- is scheduled to undergo an elective open abdominal surgical procedure under general anesthesia requiring neuromuscular relaxation using rocuronium bromide (maintenance of neuromuscular blockade if required) for endotracheal intubation and requiring neuromuscular blockade reversal;
- is scheduled to undergo a surgical procedure in a position that does not interfere with the use of TOF-Watch® SX;
- is scheduled to undergo an elective open abdominal procedure expected to last <=4 hours (from start of skin incision to end of last stitch of the skin);
- have given written informed consent.
Who cannot join
- participants for whom a difficult intubation is expected because of anatomical malformations;
- is known or suspected to have neuromuscular disorders that may impair neuromuscular blockade;
- is known or suspected to have significant renal dysfunction (e.g., creatinine clearance < 30 mL/min) ;
- is known or suspected to have significant hepatic dysfunction;
- is known or suspected to have a (family) history of malignant hyperthermia;
- is known or suspected to have an allergy to opioids, muscle relaxants or other medications used during general anesthesia;
Show all 10Show fewer
- participants for whom the use of neostigmine and/or glycopyrrolate may be contraindicated;
- participants for whom a pre-established need for postoperative intensive care admission is expected;
- pregnant or breast-feeding females;
- have participated in a previous sugammadex clinical trial;
About this study
Official title: A Multi-center, Randomized, Parallel Group, Comparative, Active Controlled, Safety-assessor Blinded, Anesthesiologist-TOF-Watch® SX Blinded Trial Comparing T4/T1 Ratio at Time of Tracheal Extubation Using 4 mg/kg Sugammadex Administered at 1-2 PTCs or Better After the Last Dose of Rocuronium Bromide to 50 µg/kg Neostigmine Administered as Per Standard of Care in Adult Subjects Undergoing Elective Open Abdominal Procedures Requiring Neuromuscular Blockade Reversal
The primary purpose of this study is to compare the incidence of
residual neuromuscular blockade at the time of tracheal extubation after reversal of rocuronium bromide-induced neuromuscular blockade by 4 mg/kg sugammadex with that of 50 µg/kg neostigmine. Residual neuromuscular blockade is defined as the fourth twitch to first twitch (T4/T1) ratio of
< 0.90.
Read the detailed description
Undetected residual neuromuscular blockade is common in the post-anesthesia care
unit (PACU). In fact, 16%-42% of patients receiving intermediate-acting muscle
relaxants in the operating room have T4/T1 ratios <0.7-0.8 in the PACU. Respiratory and pharyngeal muscle function can be adversely affected during minimal neuromuscular blockade. Studies in awake volunteers and surgical patients have demonstrated that T4/T1 ratios of 0.7 - 0.9 are associated with impaired airway protective reflexes, upper airway obstruction, a decreased hypoxic ventilatory response, and post-operative hypoxemia. The incidence and severity of residual neuromuscular blockade at the time of tracheal extubation will be evaluated to determine how these influence the length of stay in the operating room and PACU.
- Conditions
- Anesthesia
- Being tested
- Sugammadex, Neostigmine, Rocuronium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SugammadexDrug
Also called Org 25969, SCH 900616, MK-8616, Bridion®
Participants received 4 mg/kg sugammadex at 1-2 Post Tetanic Counts (PTCs) or better after the last dose of rocuronium bromide.
NeostigmineDrug
Also called Prostigmin®
Participants received 50 µg/kg neostigmine combined with 10 µg/kg glycopyrrolate after the last dose of rocuronium bromide as per standard of care.
RocuroniumDrug
Also called Rocuronium bromide, Esmeron®
Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide.
| Study group | Role | What they receive |
|---|---|---|
| Sugammadex | Experimental | 4 mg/kg sugammadex Receives: Drug: Sugammadex; Drug: Rocuronium |
| Neostigmine | Active comparator | 50 µg/kg neostigmine Receives: Drug: Neostigmine; Drug: Rocuronium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation
Neuromuscular function was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds, and assessing twitch response at the adductor pollicis muscle with a TOF-Watch® SX. The magnitudes (heights) of the first and fourth twitches (T1 and T4) were used to calculate the T4/T1 ratio, where a higher T4/T1 ratio indicates a greater recovery from neuromuscular blockade, with a value of 1.0 indicating complete recovery. After anesthesia, when neuromuscular function was expected to be fully recovered, tracheal extubation was performed, at which time the T4/T1 ratio was measured, with any missing recovery times imputed.
Measured: Up to the first 24 hours after tracheal extubation
Secondary outcomes (5)
Number of Participants With Post-operative Complications
Post-operative complications include any of the following: procedural pain, nausea, vomiting, incision-site pain, constipation, headache, pyrexia, dizziness and pruritus.
Measured: Up to 7 days after surgery
Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide
Evidence of adverse events due to a possible interaction of sugammadex with exogenous compounds or endogenous compounds other than rocuronium was recorded.
Measured: Up to 7 days after surgery
Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.9, with imputed data included.
Measured: Up to 1 hour after treatment
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.8, with imputed data included.
Measured: Up to 1 hour after treatment
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.7, with imputed data included.
Measured: Up to 1 hour after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2008 (estimated)
- Study startMay 2008
- Primary completionSep 2008
- Study completionSep 2008
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00675792
- Sponsor's protocol ID
- P05774
- Other IDs
- 19.4.334
- Status last verified
- Feb 2015
- First submitted
- 7 May 2008
- Last updated
- 13 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sabo D, Jones RK, Berry J, Sloan T, Chen J-Y, Morte JB, Groudine S. Residual neuromuscular blockade at extubation: a randomized comparison of sugammadex and neostigmine reversal of rocuronium-induced blockade in patients undergoing abdominal surgery. J Anesthe Clin Res. 2011;2:140.
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Parallel Group, Comparative, Active Controlled, Safety-assessor Blinded, Anesthesiologist-TOF-Watch® SX Blinded Trial Comparing T4/T1 Ratio at Time of Tracheal Extubation Using 4 mg/kg Sugammadex Administered at 1-2 PTCs or Better After the Last Dose of Rocuronium Bromide to 50 µg/kg Neostigmine Administered as Per Standard of Care in Adult Subjects Undergoing Elective Open Abdominal Procedures Requiring Neuromuscular Blockade Reversal
- ClinicalTrials.gov ID
- NCT00675792
- Acronym / sponsor ID
- P05774
- Conditions
- Anesthesia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 12 May 2008 (estimated)
- Results
- Posted 11 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to compare the incidence of
residual neuromuscular blockade at the time of tracheal extubation after reversal of rocuronium bromide-induced neuromuscular blockade by 4 mg/kg sugammadex with that of 50 µg/kg neostigmine. Residual neuromuscular blockade is defined as the fourth twitch to first twitch (T4/T1) ratio of
< 0.90.
Detailed description
Undetected residual neuromuscular blockade is common in the post-anesthesia care
unit (PACU). In fact, 16%-42% of patients receiving intermediate-acting muscle
relaxants in the operating room have T4/T1 ratios <0.7-0.8 in the PACU. Respiratory and pharyngeal muscle function can be adversely affected during minimal neuromuscular blockade. Studies in awake volunteers and surgical patients have demonstrated that T4/T1 ratios of 0.7 - 0.9 are associated with impaired airway protective reflexes, upper airway obstruction, a decreased hypoxic ventilatory response, and post-operative hypoxemia. The incidence and severity of residual neuromuscular blockade at the time of tracheal extubation will be evaluated to determine how these influence the length of stay in the operating room and PACU.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugammadex | Experimental | Drug: Sugammadex, Drug: Rocuronium4 mg/kg sugammadex |
| Neostigmine | Active comparator | Drug: Neostigmine, Drug: Rocuronium50 µg/kg neostigmine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- male or females who are >= 18 and <= 65 years of age
- classified by the American Society of Anesthesiologists (ASA) as Class 1 or 2 or 3;
- Body Mass Index (BMI) of <35 kg/m^2;
- is scheduled to undergo an elective open abdominal surgical procedure under general anesthesia requiring neuromuscular relaxation using rocuronium bromide (maintenance of neuromuscular blockade if required) for endotracheal intubation and requiring neuromuscular blockade reversal;
- is scheduled to undergo a surgical procedure in a position that does not interfere with the use of TOF-Watch® SX;
Key exclusion criteria (10 listed)
- participants for whom a difficult intubation is expected because of anatomical malformations;
- is known or suspected to have neuromuscular disorders that may impair neuromuscular blockade;
- is known or suspected to have significant renal dysfunction (e.g., creatinine clearance < 30 mL/min) ;
- is known or suspected to have significant hepatic dysfunction;
- is known or suspected to have a (family) history of malignant hyperthermia;
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 |
|---|---|---|
| SugammadexAlso: Org 25969, SCH 900616, MK-8616, Bridion®Participants received 4 mg/kg sugammadex at 1-2 Post Tetanic Counts (PTCs) or better after the last dose of rocuronium bromide. | Drug | Sugammadex |
| NeostigmineAlso: Prostigmin®Participants received 50 µg/kg neostigmine combined with 10 µg/kg glycopyrrolate after the last dose of rocuronium bromide as per standard of care. | Drug | Neostigmine |
| RocuroniumAlso: Rocuronium bromide, Esmeron®Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide. | Drug | Neostigmine, Sugammadex |
Primary outcome
Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation
Time frame: Up to the first 24 hours after tracheal extubation
Neuromuscular function was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds, and assessing twitch response at the adductor pollicis muscle with a TOF-Watch® SX. The magnitudes (heights) of the first and fourth twitches (T1 and T4) were used to calculate the T4/T1 ratio, where a higher T4/T1 ratio indicates a greater recovery from neuromuscular blockade, with a value of 1.0 indicating complete recovery. After anesthesia, when neuromuscular function was expected to be fully recovered, tracheal extubation was performed, at which time the T4/T1 ratio was measured, with any missing recovery times imputed.
5 secondary outcomes
Number of Participants With Post-operative Complications
Time frame: Up to 7 days after surgery
Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide
Time frame: Up to 7 days after surgery
Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9
Time frame: Up to 1 hour after treatment
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8
Time frame: Up to 1 hour after treatment
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7
Time frame: Up to 1 hour after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationSabo D, Jones RK, Berry J, Sloan T, Chen J-Y, Morte JB, Groudine S. Residual neuromuscular blockade at extubation: a randomized comparison of sugammadex and neostigmine reversal of rocuronium-induced blockade in patients undergoing abdominal surgery. J Anesthe Clin Res. 2011;2:140.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sugammadex, Neostigmine and Rocuronium in people with Anesthesia, run by Merck Sharp & Dohme LLC.
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 10 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: finished, as of the sponsor's last update on 13 Mar 2015. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Jul 2013). 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?
Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation (time frame: Up to the first 24 hours after tracheal extubation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00675792, which also lists 1 linked publication.
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 13 Mar 2015.