Underdosing of Skeletal Muscle Relaxants for LaparotomyPhase 4ProjectO5RsNCT01539044
Optimal Relaxation Technique for Laparotomies With Rocuronium Infusion Followed by Sugammadex Reversal
A Phase 4 study testing Neostigmine, atropine and Sugammadex in people with Underdosing of Skeletal Muscle Relaxants for Laparotomy and Reversal of Skeletal Muscle Relaxant, run by Hospital Sultanah Aminah Johor Bahru at 1 site in Malaysia.
Trial summary
Muscle relaxation using rocuronium infusion with sugammadex reversal hypothetically provide better quality of muscle relaxation and rapid recovery from anaesthesia compared with intermittent bolus of rocuronium muscle relaxant which is reversed with neostigmine. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Underdosing of Skeletal Muscle Relaxants for Laparotomy, Reversal of Skeletal Muscle Relaxant
- What is being tested?
- Neostigmine, atropine and Sugammadex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteMalaysia
- Study dates
- Feb 2012to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient aged 18 - 75 years old; ASA I - III;
- Elective or Semi-Emergency Laparotomy under general anaesthesia needed tracheal intubation and muscle relaxation;
Who cannot join
- Severe renal impairment (CrCL < 30 ml/ min);
- Severe hepatic impairment;
- BMI > 30 kg m2;
- Known or suspected neuromuscular disorders;
- Allergies to narcotics, muscle relaxant, benzodiazepine or other medication used during general anesthesia;
- Hypersensitivity to the active substance or to any of the excipients
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- Patient where difficult intubation was anticipated during physical examination;
- Patient who is contraindicated to epidural analgesia;
- Patient on aminoglycoside antibiotics, anticonvulsants or magnesium, as it will interfere with the action of rocuronium;
- Female patient who were pregnant, breastfeeding, or of child bearing potential and not using adequate contraception;
- Patient with poor GCS and mental derangement who is unable to give consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 4 Study of Optimal Relaxation With Rocuronium Infusion Followed by Rapid Reliable Reversal With Sugammadex: A Comparison With Conventional Practice
Muscle relaxation using rocuronium infusion with sugammadex reversal hypothetically provide better quality of muscle relaxation and rapid recovery from anaesthesia compared with intermittent bolus of rocuronium muscle relaxant which is reversed with neostigmine.
50 patients undergoing major laparotomy surgery with predicted surgical time of more than 90 minutes will be randomised into 2 treatment arms: CI-sugammadex \& IB-Neostigmine.
Read more
After a bolus of rocuronium given during induction, patients in CI-Sugammadex arm will be started on rocuronium infusion immediately and rate adjusted according to the targeted PTC of 1-2. Patients randomised to IB-Neostigmine will be given boluses of rocuronium at reappearance of TOFC of 2.
At the end of the surgery, the subject will be reversed with either sugammadex or neostigmine at different depth of block, ie PTC 1-2 and TOFC 2 respectively.
Quality of intraoperative relaxation and effectiveness of reversal of the 2 technique, CI-Sugammadex and IB-Neostigmine will be compared with respect to:
- Time to full reversal (T4/T1 [TOF] ratios ≥ 0.9) of neuromuscular blockade from:
- PTC 1-2 in CI-Sugammadex group
- TOFC ≥2 in IB-Neostigmine group
- Incidence of residual neuromuscular blockade (T4/T1 ratios < 0.9)
- Improved quality of intraoperative neuromuscular relaxation by maintaining profound neuromuscular blockade, as reflected by reduced incidence of intraoperative events and high VAS grading of relaxation quality by surgeon
Read the detailed description
Epidural will be established before induction of a standard balanced general anesthesia. After the epidural, they will be randomized into 2 groups, the CI-Sugammadex group and the IB-Neostigmine group.
Intra operative analgesia will be achieved with epidural boluses. Adjuvant drugs were administered as per routine clinical practice and their use compared between the groups.
For patients randomized to the CI-Sugammadex group, intravenous infusion of 0.3 mg/kg/hr (organon product insert) will be administered 30 minutes after the intubation dose or the return of PTC, whichever comes first. Then, the infusion rate will be titrated according to PTC (target to keep PTC between 1 to 2). Infusion rate will be increased or reduced at a rate of 0.1 mg/kg/hr if PTC is > or < than 1-2 and adequate muscle relaxation is maintained throughout the surgery. A dose of Sugammadex (4 mg/kg) will be administered at the end of the surgery (last stitch).
For patients allocated to IB-Neostigmine group, a bolus of Rocuronium at a dose of 10mg will be administered after reappearance of TOFC > 2 and depth of neuromuscular blockade will be maintained at TOFC of 1-2. At the end of surgery, a dose of Neostigmine (50mcg/kg) will be given at the reappearance of TOFC of 2.
Rescue boluses of Rocuronium will be given if clinically indicated regardless of the depth of neuromuscular block appear on the TOF-watch.
The patient will be excluded if his/her epidural fail to function and full dose of opioid is needed intra operatively for analgesia. Patients whose surgery ends before return of the first PTC 1-2 in CI-Sugammadex group or TOFC 2 in IB-Neostigmine group will also be excluded as drop outs
Central core temperature (measured by nasopharyngeal probe) will be maintained above 35°C throughout the surgery. Heart rate, oxygen saturation, blood pressure, end-tidal concentration of volatile agent and end-tidal carbon dioxide concentration will be monitored throughout the surgery.
After operation, the patient will be monitored for the peri anesthetic period in post anesthetic care unit (PACU) for at least 60min and post-anesthetic monitoring includes post-operative visit by a safety assessor and a follow-up surveillance up to 24H after surgery.
Time to full reversal (T4/T1 ratios ≥ 0.9) of neuromuscular blockade and all the secondary variables will be documented. In PACU, they will be assessed for clinical signs of adequate neuromuscular recovery and T4/T1 ratio (best of 3 readings will be recorded) to detect incidence of residual and recurrence of neuromuscular blockade. All patients' oxygen saturation, blood pressure, heart rate and respiratory rate will be monitored for 24H after the surgery and adequate analgesia provided.
Surgeons who are blinded to treatment arms will be given a visual analogue scale (VAS) to assess the quality of relaxation during the surgery immediately after he or she is ungowned at the end of surgery.
All subjects will be assessed for adverse events and serious adverse events (Itching \& erythematous reactions at the site of injection and/or generalized histaminoid reactions for example bronchospasm \& cardiovascular changes).
Patients, surgeons, post-operative assessors and nurses in the ward are blinded to group allocation. The non-blinded attending anesthetist, who is responsible for the individual patients' relaxation technique, should have no vested interest in the reversal agent or the outcome of the trial, and will not participate in postoperative clinical assessment, data entry, or statistical analysis.
- Conditions
- Underdosing of Skeletal Muscle Relaxants for Laparotomy, Reversal of Skeletal Muscle Relaxant
- Being tested
- Neostigmine, atropine, Sugammadex
- Keywords
- reversal, muscle relaxant, sugammadex
- Medical subject headings
- Muscle Hypotonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neostigmine, atropineDrug
0.05 mg/KG NEOSTIGMINE AND 0.02 MG/ KG ATROPINE at TOF 2
SugammadexDrug
Also called Bridion
4 mg/kg sugammadex will be given stat at the end of surgery at PTC 1-2
| Study group | Role | What they receive |
|---|---|---|
| IB-neostigmine | Active comparator | subject will be given intermittent bolus of rocuronium during the surgery and reversal of neostigmine at the end of surgery at TOF 2 Receives: Drug: Neostigmine, atropine |
| CI-Sugammadex | Experimental | subject will be given continuous infusion of rocuronium and reversal of sugammadex at the end of surgery at PTC 1-2 Receives: Drug: Sugammadex |
What is being measured
The primary outcome is the main question the study is designed to answer.
speed of reversal
Time from start of administration of reversal agent to recovery of the T4/T1 ratio to 0.9.
Measured: patient monitored till return of full muscle power usually within 30 mins
Secondary outcomes (3)
Vital signs, i.e. heart rate and blood pressure
pre-reversal, post-reversal, recovery and post-anesthetic visit
Measured: first 24 hours of post op period
intraoperative events
events suggestive of inadequate paralysis during surgery, a composite incidents of movement, coughing, bucking, breathing against ventilator or surgeon complaining of tight abdomen
Measured: throughout the operation averagely 3 hours
incidence of residual neuromuscular blockade
composite occurrence of clinical signs of residual muscle weakness like diplopia, ptosis, non sustained head lift, T4/T1 ratio less than 90%
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Underdosing of Skeletal Muscle Relaxants for LaparotomyStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Sultanah Aminah Johor Bahru
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Maria Lee, Hospital Sultanah Aminah Johor Bahru
- Investigators
- Dr Maria HS lee, MMed(Anaes), Principal investigator, Clinical research Centre Johor, Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01539044
- Sponsor's protocol ID
- NMRR-10-1323-7843
- Other IDs
- NMRR-10-1323-7843
- Acronym
- ProjectO5Rs
- Status last verified
- Aug 2015
- First submitted
- 15 Feb 2012
- Last updated
- 7 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 4 Study of Optimal Relaxation With Rocuronium Infusion Followed by Rapid Reliable Reversal With Sugammadex: A Comparison With Conventional Practice
- ClinicalTrials.gov ID
- NCT01539044
- Acronym / sponsor ID
- ProjectO5Rs / NMRR-10-1323-7843
- Conditions
- Underdosing of Skeletal Muscle Relaxants for Laparotomy, Reversal of Skeletal Muscle Relaxant
- Keywords
- reversal, muscle relaxant, sugammadex
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Hospital Sultanah Aminah Johor BahruOther government
- Study start
- Feb 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 27 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Muscle relaxation using rocuronium infusion with sugammadex reversal hypothetically provide better quality of muscle relaxation and rapid recovery from anaesthesia compared with intermittent bolus of rocuronium muscle relaxant which is reversed with neostigmine.
50 patients undergoing major laparotomy surgery with predicted surgical time of more than 90 minutes will be randomised into 2 treatment arms: CI-sugammadex \& IB-Neostigmine.
After a bolus of rocuronium given during induction, patients in CI-Sugammadex arm will be started on rocuronium infusion immediately and rate adjusted according to the targeted PTC of 1-2. Patients randomised to IB-Neostigmine will be given boluses of rocuronium at reappearance of TOFC of 2.
At the end of the surgery, the subject will be reversed with either sugammadex or neostigmine at different depth of block, ie PTC 1-2 and TOFC 2 respectively.
Quality of intraoperative relaxation and effectiveness of reversal of the 2 technique, CI-Sugammadex and IB-Neostigmine will be compared with respect to:
- Time to full reversal (T4/T1 [TOF] ratios ≥ 0.9) of neuromuscular blockade from:
- PTC 1-2 in CI-Sugammadex group
- TOFC ≥2 in IB-Neostigmine group
- Incidence of residual neuromuscular blockade (T4/T1 ratios < 0.9)
- Improved quality of intraoperative neuromuscular relaxation by maintaining profound neuromuscular blockade, as reflected by reduced incidence of intraoperative events and high VAS grading of relaxation quality by surgeon
Detailed description
Epidural will be established before induction of a standard balanced general anesthesia. After the epidural, they will be randomized into 2 groups, the CI-Sugammadex group and the IB-Neostigmine group.
Intra operative analgesia will be achieved with epidural boluses. Adjuvant drugs were administered as per routine clinical practice and their use compared between the groups.
For patients randomized to the CI-Sugammadex group, intravenous infusion of 0.3 mg/kg/hr (organon product insert) will be administered 30 minutes after the intubation dose or the return of PTC, whichever comes first. Then, the infusion rate will be titrated according to PTC (target to keep PTC between 1 to 2). Infusion rate will be increased or reduced at a rate of 0.1 mg/kg/hr if PTC is > or < than 1-2 and adequate muscle relaxation is maintained throughout the surgery. A dose of Sugammadex (4 mg/kg) will be administered at the end of the surgery (last stitch).
For patients allocated to IB-Neostigmine group, a bolus of Rocuronium at a dose of 10mg will be administered after reappearance of TOFC > 2 and depth of neuromuscular blockade will be maintained at TOFC of 1-2. At the end of surgery, a dose of Neostigmine (50mcg/kg) will be given at the reappearance of TOFC of 2.
Rescue boluses of Rocuronium will be given if clinically indicated regardless of the depth of neuromuscular block appear on the TOF-watch.
The patient will be excluded if his/her epidural fail to function and full dose of opioid is needed intra operatively for analgesia. Patients whose surgery ends before return of the first PTC 1-2 in CI-Sugammadex group or TOFC 2 in IB-Neostigmine group will also be excluded as drop outs
Central core temperature (measured by nasopharyngeal probe) will be maintained above 35°C throughout the surgery. Heart rate, oxygen saturation, blood pressure, end-tidal concentration of volatile agent and end-tidal carbon dioxide concentration will be monitored throughout the surgery.
After operation, the patient will be monitored for the peri anesthetic period in post anesthetic care unit (PACU) for at least 60min and post-anesthetic monitoring includes post-operative visit by a safety assessor and a follow-up surveillance up to 24H after surgery.
Time to full reversal (T4/T1 ratios ≥ 0.9) of neuromuscular blockade and all the secondary variables will be documented. In PACU, they will be assessed for clinical signs of adequate neuromuscular recovery and T4/T1 ratio (best of 3 readings will be recorded) to detect incidence of residual and recurrence of neuromuscular blockade. All patients' oxygen saturation, blood pressure, heart rate and respiratory rate will be monitored for 24H after the surgery and adequate analgesia provided.
Surgeons who are blinded to treatment arms will be given a visual analogue scale (VAS) to assess the quality of relaxation during the surgery immediately after he or she is ungowned at the end of surgery.
All subjects will be assessed for adverse events and serious adverse events (Itching \& erythematous reactions at the site of injection and/or generalized histaminoid reactions for example bronchospasm \& cardiovascular changes).
Patients, surgeons, post-operative assessors and nurses in the ward are blinded to group allocation. The non-blinded attending anesthetist, who is responsible for the individual patients' relaxation technique, should have no vested interest in the reversal agent or the outcome of the trial, and will not participate in postoperative clinical assessment, data entry, or statistical analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IB-neostigmine | Active comparator | Drug: Neostigmine, atropinesubject will be given intermittent bolus of rocuronium during the surgery and reversal of neostigmine at the end of surgery at TOF 2 |
| CI-Sugammadex | Experimental | Drug: Sugammadexsubject will be given continuous infusion of rocuronium and reversal of sugammadex at the end of surgery at PTC 1-2 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient aged 18 - 75 years old; ASA I - III;
- Elective or Semi-Emergency Laparotomy under general anaesthesia needed tracheal intubation and muscle relaxation;
Key exclusion criteria (11 listed)
- Severe renal impairment (CrCL < 30 ml/ min);
- Severe hepatic impairment;
- BMI > 30 kg m2;
- Known or suspected neuromuscular disorders;
- Allergies to narcotics, muscle relaxant, benzodiazepine or other medication used during general anesthesia;
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 |
|---|---|---|
| Neostigmine, atropine0.05 mg/KG NEOSTIGMINE AND 0.02 MG/ KG ATROPINE at TOF 2 | Drug | IB-neostigmine |
| SugammadexAlso: Bridion4 mg/kg sugammadex will be given stat at the end of surgery at PTC 1-2 | Drug | CI-Sugammadex |
Primary outcome
speed of reversal
Time frame: patient monitored till return of full muscle power usually within 30 mins
Time from start of administration of reversal agent to recovery of the T4/T1 ratio to 0.9.
3 secondary outcomes
Vital signs, i.e. heart rate and blood pressure
Time frame: first 24 hours of post op period
intraoperative events
Time frame: throughout the operation averagely 3 hours
incidence of residual neuromuscular blockade
Time frame: 1 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2015.
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.
Dr Maria HS lee, MMed(Anaes) principal investigator
Clinical research Centre Johor, Malaysia
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 Neostigmine, atropine and Sugammadex in people with Underdosing of Skeletal Muscle Relaxants for Laparotomy and Reversal of Skeletal Muscle Relaxant, run by Hospital Sultanah Aminah Johor Bahru at 1 site in Malaysia.
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 2 inclusion and 11 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 7 Aug 2015. 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 Malaysia. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
speed of reversal (time frame: patient monitored till return of full muscle power usually within 30 mins). 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 7 Aug 2015.