Anesthesia, GeneralPhase 3NCT00451217

Comparison of Sugammadex (Org 25969) With Neostigmine as Reversal Agents for Rocuronium or Vecuronium at Reappearance of T2 (P05960)

A Phase 3 study testing Sugammadex and Neostigmine in people with Anesthesia, General, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study was to demonstrate in adult participants faster recovery from a neuromuscular block induced by either rocuronium or vecuronium after reversal at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Anesthesia, General
What is being tested?: Sugammadex and Neostigmine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 198 participants
Where: No sites listed yet
Study dates: 17 Nov 2005to 6 Mar 2006
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Is of American Society of Anesthesiologists (ASA) 1 - 4;
Is above or equal to the age of 18;
Scheduled for surgical procedures with a general anesthesia with the use of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block;
Scheduled for surgical procedure in supine position;
Given written informed consent.

Who cannot join

Participants in whom a difficult intubation because of anatomical malformations was expected;
Is known or suspected to have neuromuscular disorders impairing neuromuscular block (NMB) and/or significant renal dysfunction;
Is known or suspected to have a (family) history of malignant hyperthermia;
Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
Is receiving medication in a dose and/or at a time point known to interfere with neuromuscular blocking agents such as antibiotics, anticonvulsants and Mg2+;
Participants in whom the use of neostigmine and/or glycopyrrolate may be contraindicated;

Show all 11Show fewer

Had already participated in a sugammadex trial;
Had participated in another clinical trial, not pre-approved by NV Organon, within 30 days of entering into P05960.
Females who are pregnant:
Females of childbearing potential not using any method of birth control: condom or using only hormonal contraception as birth control;
Females who were breast-feeding.

About this study

Official title: A Multi -Center Randomized Parallel Group Comparative Active Controlled Safety Assessor Blinded Phase 3a Pivotal Trial in Adult Subjects Comparing Org 25969 With Neostigmine as Reversal Agents of a Neuromuscular Block Induced by Rocuronium or Vecuronium at Reappearance of T2

Conditions: Anesthesia, General
Being tested: Sugammadex, Neostigmine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SugammadexDrug
Also called Org 25969
After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was to be administered
NeostigmineDrug
Also called premix neostigmine/glycopyrrolate
After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was to be administered

Study groups in NCT00451217
Study group	Role	What they receive
Rocuronium + Sugammadex	Experimental	After the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered Receives: Drug: Sugammadex
Rocuronium + Neostigmine	Active comparator	After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered Receives: Drug: Neostigmine
Vecuronium + Sugammadex	Experimental	After the last dose of vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered Receives: Drug: Sugammadex
Vecuronium + Neostigmine	Active comparator	After the last dose of vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered Receives: Drug: Neostigmine

What is being measured

The primary outcome is the main question the study is designed to answer.

Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9.
Neuromuscular functioning 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. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached >= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB.
Measured: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9

Secondary outcomes (4)

Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB.
Measured: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.7
Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB.
Measured: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.8
Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Transfer to the Recovery Room After Extubation
After anesthesia and prior to transfer to the recovery room after extubation, neuromuscular recovery was assessed by monitoring every 15 minutes the following clinical signs of recovery: level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation); 5-second head lift test (ability to lift the head for 5 seconds); and general muscle weakness
Measured: Day 1
Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Discharge From the Recovery Room
Just prior to discharge from the recovery room, neuromuscular recovery was assessed by monitoring every 15 minutes the following clinical signs of recovery: level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation); 5-second head lift test (ability to lift the head for 5 seconds); and general muscle weakness
Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Nov 20056 Mar 2006

First posted23 Mar 2007 (estimated)
Study start17 Nov 2005
Primary completion6 Mar 2006
Study completion6 Mar 2006

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 (2)Papers the sponsor has linked to this study.
Other trials for Anesthesia, GeneralStudies 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: None (open label)
Enrolment: 198 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00451217
Sponsor's protocol ID: P05960
Other IDs: 19.4.301, MK-8616-033
Status last verified: Feb 2019
First submitted: 22 Mar 2007
Last updated: 4 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H, Alvarez-Gomez JA. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010 Jan 1;110(1):64-73. doi: 10.1213/ane.0b013e3181ac53c3. Epub 2009 Aug 27.
PubMed 19713265
Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010 Oct;27(10):874-81. doi: 10.1097/EJA.0b013e32833d56b7.
PubMed 20683334

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 4 Mar 2019. 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 Phase 3a Pivotal Trial in Adult Subjects Comparing Org 25969 With Neostigmine as Reversal Agents of a Neuromuscular Block Induced by Rocuronium or Vecuronium at Reappearance of T2
ClinicalTrials.gov ID: NCT00451217
Acronym / sponsor ID: P05960
Conditions: Anesthesia, General
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 198 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 17 Nov 2005 (actual)
Primary completion: 6 Mar 2006 (actual)
Study completion: 6 Mar 2006 (actual)
First posted: 23 Mar 2007 (estimated)
Results: Posted 18 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Rocuronium + Sugammadex	Experimental	Drug: SugammadexAfter the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered
Rocuronium + Neostigmine	Active comparator	Drug: NeostigmineAfter the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered
Vecuronium + Sugammadex	Experimental	Drug: SugammadexAfter the last dose of vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered
Vecuronium + Neostigmine	Active comparator	Drug: NeostigmineAfter the last dose of vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Is of American Society of Anesthesiologists (ASA) 1 - 4;
Is above or equal to the age of 18;
Scheduled for surgical procedures with a general anesthesia with the use of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block;
Scheduled for surgical procedure in supine position;
Given written informed consent.

Key exclusion criteria (11 listed)

Participants in whom a difficult intubation because of anatomical malformations was expected;
Is known or suspected to have neuromuscular disorders impairing neuromuscular block (NMB) and/or significant renal dysfunction;
Is known or suspected to have a (family) history of malignant hyperthermia;
Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia;
Is receiving medication in a dose and/or at a time point known to interfere with neuromuscular blocking agents such as antibiotics, anticonvulsants and Mg2+;

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 25969After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was to be administered	Drug	Rocuronium + Sugammadex, Vecuronium + Sugammadex
NeostigmineAlso: premix neostigmine/glycopyrrolateAfter the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was to be administered	Drug	Rocuronium + Neostigmine, Vecuronium + Neostigmine

Primary outcome

Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9.
Time frame: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9
Neuromuscular functioning 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. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached >= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB.

4 secondary outcomes

Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7
Time frame: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.7
Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8
Time frame: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.8
Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Transfer to the Recovery Room After Extubation
Time frame: Day 1
Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Discharge From the Recovery Room
Time frame: Day 1

Results and safety

Results posted to the registry on 18 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rocuronium + Sugammadex	49	47
Rocuronium + Neostigmine	49	47
Vecuronium + Sugammadex	51	47
Vecuronium + Neostigmine	49	44

Primary outcome: Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9.

Time frame: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9. Mean (Standard Deviation). Unit: Minutes

Measure	Rocuronium + Sugammadex n = 48	Rocuronium + Neostigmine n = 48	Vecuronium + Sugammadex n = 48	Vecuronium + Neostigmine n = 45
Value	1.62 (0.83)	26.78 (24.60)	4.47 (9.28)	23.43 (18.53)

Population analysed: All randomized participants who received sugammadex or neostigmine and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 7 days after sugammadex or neostigmine treatment. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rocuronium + Sugammadex	2 of 48 (4.2%)	37 of 48 (77.1%)	0 of 48
Rocuronium + Neostigmine	3 of 48 (6.3%)	40 of 48 (83.3%)	0 of 48
Vecuronium + Sugammadex	0 of 48 (0%)	32 of 48 (66.7%)	0 of 48
Vecuronium + Neostigmine	0 of 45 (0%)	35 of 45 (77.8%)	0 of 45

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 19713265Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H, Alvarez-Gomez JA. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010 Jan 1;110(1):64-73. doi: 10.1213/ane.0b013e3181ac53c3. Epub 2009 Aug 27.
Derived from this study: PubMed 20683334Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010 Oct;27(10):874-81. doi: 10.1097/EJA.0b013e32833d56b7.
Click here to access a synopsis of the study results.Link provided by the sponsor.

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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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sugammadex and Neostigmine in people with Anesthesia, General, 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 5 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 4 Mar 2019. 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 18 Feb 2019). 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?

Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9. (time frame: Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9). 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 NCT00451217, which also lists 2 linked publications.

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 4 Mar 2019.