Incomplete Reversal of Neuromuscular BlockPhase 4NCT02568345

Sugammadex ED90 Dose in the Obese Patients

A Phase 4 study testing sugammadex ED90 in people with Incomplete Reversal of Neuromuscular Block, run by Faculdade de Ciências Médicas da Santa Casa de São Paulo.

Completed

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

Official record

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Trial summary

The purpose of this study is to determine the minimum effective dose of sugammadex, an antagonist of neuromuscular blockade used during anesthesia practice, in obese patients, considering that sugammadex is indicated in adults with normal weight at a dose of 2 mg/kg but no studies were found with obese patients. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Incomplete Reversal of Neuromuscular Block
What is being tested?: sugammadex ED90
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: No sites listed yet
Study dates: Jan 2013to Jan 2014
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 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

a body mass index ≥ 40 kg/m2
bariatric surgery
informed consent signed

Who cannot join

history of neuromuscular diseases,
use of drugs that could interfere with neuromuscular transmission,
allergy to neuromuscular agents of the aminosteroids class,
anticipated difficulty in airway management,
renal failure

About this study

Official title: Sugammadex ED90 Dose to Reverse the Rocuronium Blockade in the Obese Patients

Read the detailed description

Prospective study with the sequential design method up-and-down of the biased coin aimed to determine the minimum effective dose in 90% of patients (ED90).

The following doses were chosen: 2.0 mg.kg-1, 2.2 mg.kg-1, 2.4 mg.kg-1, 2.6 mg.kg-1, 2.8 mg.kg-1.

The complete reversal of moderate rocuronium-induced neuromuscular blockade (NMB) considered a T4/T1 ratio ≥ 0.9 with the peripheral nerve stimulator and accelerometer (monitor of sequential electric stimuli) "train-of-four" (TOF).

After induction of general anesthesia and the calibration of the peripheral nerve stimulator and accelerometer, rocuronium 0.6 mg.kg-1 was injected.

Continuous intravenous infusion of the anesthetics propofol and remifentanil, and intermittent bolus of rocuronium were offered throughout the procedure.

Conditions: Incomplete Reversal of Neuromuscular Block
Being tested: sugammadex ED90
Keywords: Dose-Response Relationship, Drug, Obesity, Cyclodextrins
Medical subject headings: Obesity

What participants receive

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

sugammadex ED90Drug
Also called ED90
The first patient received the dose of 2.4 mg/kg and if there was a negative response, the next patient would be allocated to receive the next higher dose of 2.6 mg/kg.
In case that 2.4 mg/kg did produce a positive response, the next patient would be randomized with 10% of probability to receive the next dose of 2.2 mg/kg or 90% probability to receive the same dose of 2.4 mg/kg.

Study groups in NCT02568345
Study group	Role	What they receive
sugammadex ED90	Experimental	Sequential design method up-and-down of the biased coin aimed to determine the minimum effective dose in 90% of patients (ED90). The following doses were chosen: 2.0 mg/kg, 2.2 mg/kg, 2.4 mg/kg, 2.6 mg/kg, 2.8 mg/kg. Receives: Drug: sugammadex ED90

What is being measured

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

Sugammadex ED90
Complete reversal of neuromuscular blockade occured when the patient had a TOF T4/T1 ≥ 0.9 within eight minutes of sugammadex infusion.
The sequencial design method of up-and-down was applied to determine the minimum effective dose in 90% of patients (ED90). An effective dose is one that achieves complete reversal of neuromuscular blockade that is defined as a measure of TOF equal or higher than 0.9, or a relationship between T4 an T1 measure ≥ 0.9, within eight minutes of sugammadex infusion.
Measured: 8 minutes

Timeline

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

Jan 2013Jan 2014

First posted5 Oct 2015 (estimated)
Study startJan 2013
Primary completionOct 2013
Study completionJan 2014

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 (26)Papers the sponsor has linked to this study.
Other trials for Incomplete Reversal of Neuromuscular BlockStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02568345
Sponsor's protocol ID: 191.837
Status last verified: Jan 2016
First submitted: 2 Oct 2015
Last updated: 22 Feb 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes

Publications

1983 metropolitan height and weight tables. Stat Bull Metrop Life Found. 1983 Jan-Jun;64(1):3-9. No abstract available.
PubMed 6623350
Abernethy DR, Greenblatt DJ, Divoll M, Smith RB, Shader RI. The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clin Pharmacokinet. 1984 Mar-Apr;9(2):177-83. doi: 10.2165/00003088-198409020-00005.
PubMed 6143633
Blouin RA, Kolpek JH, Mann HJ. Influence of obesity on drug disposition. Clin Pharm. 1987 Sep;6(9):706-14.
PubMed 3315402
de Boer HD, Driessen JJ, Marcus MA, Kerkkamp H, Heeringa M, Klimek M. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study. Anesthesiology. 2007 Aug;107(2):239-44. doi: 10.1097/01.anes.0000270722.95764.37.
PubMed 17667567
Donati F. Sugammadex: a cyclodextrin to reverse neuromuscular blockade in anaesthesia. Expert Opin Pharmacother. 2008 Jun;9(8):1375-86. doi: 10.1517/14656566.9.8.1375.
PubMed 18473711
Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM. A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet. 2004;43(15):1167-78. doi: 10.2165/00003088-200443150-00007.
PubMed 15568893
Epemolu O, Bom A, Hope F, Mason R. Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Anesthesiology. 2003 Sep;99(3):632-7; discussion 6A. doi: 10.1097/00000542-200309000-00018.
PubMed 12960547
Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051-65. doi: 10.2165/00003088-200544100-00004.
PubMed 16176118
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987 Oct 22;317(17):1098. doi: 10.1056/NEJM198710223171717. No abstract available.
PubMed 3657876
Nicholson WT, Sprung J, Jankowski CJ. Sugammadex: a novel agent for the reversal of neuromuscular blockade. Pharmacotherapy. 2007 Aug;27(8):1181-8. doi: 10.1592/phco.27.8.1181.
PubMed 17655516
Pai MP, Paloucek FP. The origin of the "ideal" body weight equations. Ann Pharmacother. 2000 Sep;34(9):1066-9. doi: 10.1345/aph.19381.
PubMed 10981254
Renes SH, van Geffen GJ, Rettig HC, Gielen MJ, Scheffer GJ. Minimum effective volume of local anesthetic for shoulder analgesia by ultrasound-guided block at root C7 with assessment of pulmonary function. Reg Anesth Pain Med. 2010 Nov-Dec;35(6):529-34. doi: 10.1097/AAP.0b013e3181fa1190.
PubMed 20975468
Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Ostergaard D, Prins ME, Viby-Mogensen J. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006 Apr;104(4):667-74. doi: 10.1097/00000542-200604000-00009.
PubMed 16571960
Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics. 2002 Mar;58(1):171-7. doi: 10.1111/j.0006-341x.2002.00171.x.
PubMed 11890313
Demirkaya M, Kelsaka E, Sarihasan B, Bek Y, Ustun E. The optimal dose of remifentanil for acceptable intubating conditions during propofol induction without neuromuscular blockade. J Clin Anesth. 2012 Aug;24(5):392-7. doi: 10.1016/j.jclinane.2011.11.006.
PubMed 22748212

Study at a glance

From the registry record, last updated by the sponsor on 22 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Sugammadex ED90 Dose to Reverse the Rocuronium Blockade in the Obese Patients
ClinicalTrials.gov ID: NCT02568345
Acronym / sponsor ID: 191.837
Conditions: Incomplete Reversal of Neuromuscular Block
Keywords: Dose-Response Relationship, Drug, Obesity, Cyclodextrins
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Faculdade de Ciências Médicas da Santa Casa de São PauloUniversity, hospital or other
Study start: Jan 2013
Primary completion: Oct 2013 (actual)
Study completion: Jan 2014 (actual)
First posted: 5 Oct 2015 (estimated)
Results: Posted 22 Feb 2016

Clinical summary

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

Detailed description

Prospective study with the sequential design method up-and-down of the biased coin aimed to determine the minimum effective dose in 90% of patients (ED90).

The following doses were chosen: 2.0 mg.kg-1, 2.2 mg.kg-1, 2.4 mg.kg-1, 2.6 mg.kg-1, 2.8 mg.kg-1.

After induction of general anesthesia and the calibration of the peripheral nerve stimulator and accelerometer, rocuronium 0.6 mg.kg-1 was injected.

Continuous intravenous infusion of the anesthetics propofol and remifentanil, and intermittent bolus of rocuronium were offered throughout the procedure.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
sugammadex ED90	Experimental	Drug: sugammadex ED90Sequential design method up-and-down of the biased coin aimed to determine the minimum effective dose in 90% of patients (ED90). The following doses were chosen: 2.0 mg/kg, 2.2 mg/kg, 2.4 mg/kg, 2.6 mg/kg, 2.8 mg/kg.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (3 listed)

a body mass index ≥ 40 kg/m2
bariatric surgery
informed consent signed

Key exclusion criteria (5 listed)

history of neuromuscular diseases,
use of drugs that could interfere with neuromuscular transmission,
allergy to neuromuscular agents of the aminosteroids class,
anticipated difficulty in airway management,
renal failure

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
sugammadex ED90Also: ED90The first patient received the dose of 2.4 mg/kg and if there was a negative response, the next patient would be allocated to receive the next higher dose of 2.6 mg/kg. In case that 2.4 mg/kg did produce a positive response, the next patient would be randomized with 10% of probability to receive the next dose of 2.2 mg/kg or 90% probability to receive the same dose of 2.4 mg/kg.	Drug	sugammadex ED90

Primary outcome

Sugammadex ED90
Time frame: 8 minutes
Complete reversal of neuromuscular blockade occured when the patient had a TOF T4/T1 ≥ 0.9 within eight minutes of sugammadex infusion. The sequencial design method of up-and-down was applied to determine the minimum effective dose in 90% of patients (ED90). An effective dose is one that achieves complete reversal of neuromuscular blockade that is defined as a measure of TOF equal or higher than 0.9, or a relationship between T4 an T1 measure ≥ 0.9, within eight minutes of sugammadex infusion.

Results and safety

Results posted to the registry on 22 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sugammadex ED90	31	31

Primary outcome: Sugammadex ED90

Time frame: 8 minutes. Number (99% Confidence Interval). Unit: mg/kg

Measure	Sugammadex ED90 n = 31
Value	2.40 (2.20 to 2.60)

Sugammadex ED90: isotonic regression functions through PA: 2.20

Adverse events

Time frame: 24 hours. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sugammadex ED90	0 of 31 (0%)	0 of 31 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 66233501983 metropolitan height and weight tables. Stat Bull Metrop Life Found. 1983 Jan-Jun;64(1):3-9. No abstract available.
Background: PubMed 6143633Abernethy DR, Greenblatt DJ, Divoll M, Smith RB, Shader RI. The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clin Pharmacokinet. 1984 Mar-Apr;9(2):177-83. doi: 10.2165/00003088-198409020-00005.
Background: PubMed 3315402Blouin RA, Kolpek JH, Mann HJ. Influence of obesity on drug disposition. Clin Pharm. 1987 Sep;6(9):706-14.
Background: PubMed 17667567de Boer HD, Driessen JJ, Marcus MA, Kerkkamp H, Heeringa M, Klimek M. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study. Anesthesiology. 2007 Aug;107(2):239-44. doi: 10.1097/01.anes.0000270722.95764.37.
Background: PubMed 18473711Donati F. Sugammadex: a cyclodextrin to reverse neuromuscular blockade in anaesthesia. Expert Opin Pharmacother. 2008 Jun;9(8):1375-86. doi: 10.1517/14656566.9.8.1375.
Background: PubMed 15568893Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CM. A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet. 2004;43(15):1167-78. doi: 10.2165/00003088-200443150-00007.
Background: PubMed 12960547Epemolu O, Bom A, Hope F, Mason R. Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Anesthesiology. 2003 Sep;99(3):632-7; discussion 6A. doi: 10.1097/00000542-200309000-00018.
Background: PubMed 16176118Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051-65. doi: 10.2165/00003088-200544100-00004.
Background: PubMed 3657876Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987 Oct 22;317(17):1098. doi: 10.1056/NEJM198710223171717. No abstract available.
Background: PubMed 17655516Nicholson WT, Sprung J, Jankowski CJ. Sugammadex: a novel agent for the reversal of neuromuscular blockade. Pharmacotherapy. 2007 Aug;27(8):1181-8. doi: 10.1592/phco.27.8.1181.
Background: PubMed 10981254Pai MP, Paloucek FP. The origin of the "ideal" body weight equations. Ann Pharmacother. 2000 Sep;34(9):1066-9. doi: 10.1345/aph.19381.
Background: PubMed 20975468Renes SH, van Geffen GJ, Rettig HC, Gielen MJ, Scheffer GJ. Minimum effective volume of local anesthetic for shoulder analgesia by ultrasound-guided block at root C7 with assessment of pulmonary function. Reg Anesth Pain Med. 2010 Nov-Dec;35(6):529-34. doi: 10.1097/AAP.0b013e3181fa1190.
Individual participant dataSharing planned: Yes

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.

Lígia Andrade ST Mathias, MD, Ph.D study director

Full professor

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing sugammadex ED90 in people with Incomplete Reversal of Neuromuscular Block, run by Faculdade de Ciências Médicas da Santa Casa de São Paulo.

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 3 inclusion and 5 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 22 Feb 2016. 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 22 Feb 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?

Sugammadex ED90 (time frame: 8 minutes). 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 NCT02568345, which also lists 26 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 22 Feb 2016.