Airway Reflexes, ProtectivePhase 4NCT01199237

Impact of Anesthetic Choice (Sevoflurane Versus Desflurane) on Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block

A Phase 4 study testing Sevoflurane, Desflurane and Rocuronium in people with Airway Reflexes, Protective and Recovery After Neuromuscular Block, run by University of California, San Francisco at 2 sites in United States.

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

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Airway Reflexes, Protective, Recovery After Neuromuscular Block, Anesthetic Recovery
What is being tested?: Sevoflurane, Desflurane and Rocuronium
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 107 participants
Where: 2 sitesUnited States
Study dates: Aug 2010to Aug 2013
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

ASA 1-2 patients
Age 18-65 years
body mass index (BMI) ≤ 35kg/m2
Planned surgery requiring general anesthesia lasting approximately 1.5-3.0 hours
Surgery requires or benefits from skeletal muscle relaxation
All must pass the baseline 20 mL water swallowing test as previously described.

Who cannot join

Pre-existing neuromuscular or central nervous system disorder
Known condition interfering with gastric emptying
Planned surgical procedure on the head or neck
Known liver disease
Serum creatinine > 1.5 mg/dL
Concurrent use of neuroleptic medications

Show all 10Show fewer

Contraindication or previous adverse response to any of the study drugs
Active asthma or reactive airways disease
Surgery where upright position or brief cough would be contraindicated
Inability to provide informed consent

Trial locations and contacts

2 sites in 1 country.

United States2 sites

UCSF Helen Diller Cancer Center
San Francisco, California, 94115
UCSF Moffitt-Long Hospital
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Effect of Anesthetic Choice (Sevoflurane Versus Desflurane) on Speed and Sustained Nature of Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block

Protective airway reflexes may be impaired in the postoperative period, creating the potential for aspiration of gastric contents, even after a patient exhibits appropriate response to command. Because assessment of airway reflex recovery is not possible in an intubated patient, the clinician must make an empiric decision as to when a patient is safe to extubate, and choose a combination of techniques least likely to result in pharyngeal impairment. Adequacy of reversal of neuromuscular block by cholinesterase inhibitors (e.g., neostigmine) is unpredictable, especially in the presence of profound paralysis, and tactile assessment of train-of four and sustained tetanus has shown poor correlation with objective assessments. Protective airway reflexes may also be impaired during early recovery by the anesthetics themselves, even when muscle relaxant has been avoided. In the absence of muscle relaxant the investigators previously demonstrated that patients receiving an anesthetic with higher tissue solubility, sevoflurane showed significantly greater impairment of swallowing up to 14 minutes after response to command compared to patients receiving an anesthetic with lower tissue solubility, desflurane. Therefore, we ask whether the combination of the more soluble anesthetic and the presence of neuromuscular block antagonized by neostigmine may create a multiplicative effect that might further prolong pharyngeal recovery. We plan to randomly assign 100 patients scheduled to undergo surgery with general anesthesia to a standardized anesthetic that includes 1) sevoflurane, rocuronium with 70 µg/kg neostigmine + 14 µg/kg glycopyrrolate antagonism (group S); or 2) desflurane, rocuronium with 70 µg/kg neostigmine + 14 µg/kg glycopyrrolate antagonism (group D). Airway reflex recovery will be judged as adequate by the patient's ability to swallow 20 mL of water without coughing or drooling 5, 10, 15, 20, 30 and 60 minutes after response to command. Anesthetic (sevoflurane or desflurane) will be discontinued after administration of reversal agent and recovery to TOF (train-of-four) ratio of 0.7.

Conditions: Airway Reflexes, Protective, Recovery After Neuromuscular Block, Anesthetic Recovery
Being tested: Sevoflurane, Desflurane, Rocuronium, Neostigmine, Glycopyrrolate
Keywords: Reflex, Pharyngeal, Anesthetics, Inhalation
Medical subject headings: Gagging, Respiratory Aspiration

What participants receive

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

SevofluraneDrug
Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water
DesfluraneDrug
Protective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water
RocuroniumDrug
NeostigmineDrug
GlycopyrrolateDrug

Study groups in NCT01199237
Study group	Role	What they receive
Sevoflurane	Active comparator	Patients receive sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) Receives: Drug: Sevoflurane; Drug: Rocuronium; Drug: Neostigmine; Drug: Glycopyrrolate
Desflurane	Active comparator	Patients receive Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg) Receives: Drug: Desflurane; Drug: Rocuronium; Drug: Neostigmine; Drug: Glycopyrrolate

What is being measured

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

Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis.
The patient is judged by the primary anesthetist to be awake at time T1. At 2 minutes after T1, the patient was asked to swallow 20mL of water from a paper cup, and a blinded observer judged the ability to swallow based on transit of water to the posterior pharynx (absence of pooling or drooling) and absence of cough or gag.
Measured: At 2 minutes after response to command (T1).

Secondary outcomes (4)

Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1)
At the conclusion of surgery, after the patient's potent inhaled anesthetic was discontinued, the commands "open your eyes" and "squeeze my hand" were given at 30-second intervals. The time at which patient first appropriately response to both commands was noted as T1.
Measured: Up to 1 hour post-operative
Nausea and Vomiting
Patients were asked to rate their experience of nausea and vomiting on a 0-10 verbal analog scale, with 0 being absence and 10 being the worst imaginable
Measured: 30 minutes after T1
Nausea and Vomiting
Patients were asked to rate their experience of nausea and vomiting on a 0-10 verbal analog scale, with 0 being absence and 10 being the worst imaginable
Measured: 60 minutes after T1
Time From Anesthetic Discontinuation to First Ability to Swallow
At 2 minutes after first response to command (T1), the patient was asked to swallow 20 mL of water from a paper cup, and an observer blinded to anesthetic assignment assessed the ability to swallow based on transit of water to the posterior pharynx (absence of pooling or drooling) and absence of cough or gag (indicating misdirection of the water bolus into the laryngeal inlet). This test was repeated at 6, 14, 22, 30 and 60 minutes after the time of first response to command.
Measured: up to 60 minutes after T1

Timeline

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

Aug 2010Aug 2013

First posted10 Sep 2010 (estimated)
Study startAug 2010
Primary completionAug 2012
Study completionAug 2013

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 (6)Papers the sponsor has linked to this study.
Other trials for Airway Reflexes, ProtectiveStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe 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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 107 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01199237
Sponsor's protocol ID: H10722-35629-01
Status last verified: May 2014
First submitted: 23 Aug 2010
Last updated: 16 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84. doi: 10.1097/00000542-200004000-00014.
PubMed 10754616
Sundman E, Witt H, Sandin R, Kuylenstierna R, Boden K, Ekberg O, Eriksson LI. Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry. Anesthesiology. 2001 Nov;95(5):1125-32. doi: 10.1097/00000542-200111000-00016.
PubMed 11684981
Mckay RE, Large MJC, Balea MC, Mckay WR. Airway reflexes return more rapidly after desflurane anesthesia than after sevoflurane anesthesia. Anesth Analg. 2005 Mar;100(3):697-700. doi: 10.1213/01.ANE.0000146514.65070.AE.
PubMed 15728054
McKay RE, Malhotra A, Cakmakkaya OS, Hall KT, McKay WR, Apfel CC. Effect of increased body mass index and anaesthetic duration on recovery of protective airway reflexes after sevoflurane vs desflurane. Br J Anaesth. 2010 Feb;104(2):175-82. doi: 10.1093/bja/aep374. Epub 2009 Dec 26.
PubMed 20037150
Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268.
PubMed 18635478
DePippo KL, Holas MA, Reding MJ. Validation of the 3-oz water swallow test for aspiration following stroke. Arch Neurol. 1992 Dec;49(12):1259-61. doi: 10.1001/archneur.1992.00530360057018.
PubMed 1449405

Study at a glance

From the registry record, last updated by the sponsor on 16 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Anesthetic Choice (Sevoflurane Versus Desflurane) on Speed and Sustained Nature of Airway Reflex Recovery in the Context of Antagonized Neuromuscular Block
ClinicalTrials.gov ID: NCT01199237
Acronym / sponsor ID: H10722-35629-01
Conditions: Airway Reflexes, Protective, Recovery After Neuromuscular Block, Anesthetic Recovery
Keywords: Reflex, Pharyngeal, Anesthetics, Inhalation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 107 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: Baxter Healthcare Corporation
Study start: Aug 2010
Primary completion: Aug 2012 (actual)
Study completion: Aug 2013 (actual)
First posted: 10 Sep 2010 (estimated)
Results: Posted 8 May 2014

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: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Sevoflurane	Active comparator	Drug: Sevoflurane, Drug: Rocuronium, Drug: Neostigmine, Drug: GlycopyrrolatePatients receive sevoflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg)
Desflurane	Active comparator	Drug: Desflurane, Drug: Rocuronium, Drug: Neostigmine, Drug: GlycopyrrolatePatients receive Desflurane, rocuronium with neostigmine + glycopyrrolate reversal (70 and 14 ug/kg)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

ASA 1-2 patients
Age 18-65 years
body mass index (BMI) ≤ 35kg/m2
Planned surgery requiring general anesthesia lasting approximately 1.5-3.0 hours
Surgery requires or benefits from skeletal muscle relaxation

Key exclusion criteria (10 listed)

Pre-existing neuromuscular or central nervous system disorder
Known condition interfering with gastric emptying
Planned surgical procedure on the head or neck
Known liver disease
Serum creatinine > 1.5 mg/dL

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
SevofluraneProtective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water	Drug	Sevoflurane
DesfluraneProtective airway reflexes will be tested, judged by subject's ability to swallow 20 mL water	Drug	Desflurane
Rocuronium	Drug	Desflurane, Sevoflurane
Neostigmine	Drug	Desflurane, Sevoflurane
Glycopyrrolate	Drug	Desflurane, Sevoflurane

Primary outcome

Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis.
Time frame: At 2 minutes after response to command (T1).
The patient is judged by the primary anesthetist to be awake at time T1. At 2 minutes after T1, the patient was asked to swallow 20mL of water from a paper cup, and a blinded observer judged the ability to swallow based on transit of water to the posterior pharynx (absence of pooling or drooling) and absence of cough or gag.

4 secondary outcomes

Time From Potent Inhaled Anesthetic Discontinuation to First Response to Command (T1)
Time frame: Up to 1 hour post-operative
Nausea and Vomiting
Time frame: 30 minutes after T1
Nausea and Vomiting
Time frame: 60 minutes after T1
Time From Anesthetic Discontinuation to First Ability to Swallow
Time frame: up to 60 minutes after T1

Results and safety

Results posted to the registry on 8 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sevoflurane	41	41
Desflurane	40	40

Primary outcome: Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis.

Time frame: At 2 minutes after response to command (T1).. Number. Unit: participants

Measure	Sevoflurane n = 26	Desflurane n = 31
able to swallow at T1+2 minutes	16	25
unable to swallow at T1+2 minutes	10	6

Sevoflurane vs Desflurane: p = 0.11, Chi-squared

Population analysed: Only participants judged by the clinician as able to take the test (n=57)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1-2 hours postoperatively. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sevoflurane	0 of 41 (0%)	0 of 41 (0%)	Not reported
Desflurane	0 of 40 (0%)	0 of 40 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 10754616Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology. 2000 Apr;92(4):977-84. doi: 10.1097/00000542-200004000-00014.
Background: PubMed 11684981Sundman E, Witt H, Sandin R, Kuylenstierna R, Boden K, Ekberg O, Eriksson LI. Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry. Anesthesiology. 2001 Nov;95(5):1125-32. doi: 10.1097/00000542-200111000-00016.
Background: PubMed 15728054Mckay RE, Large MJC, Balea MC, Mckay WR. Airway reflexes return more rapidly after desflurane anesthesia than after sevoflurane anesthesia. Anesth Analg. 2005 Mar;100(3):697-700. doi: 10.1213/01.ANE.0000146514.65070.AE.
Background: PubMed 20037150McKay RE, Malhotra A, Cakmakkaya OS, Hall KT, McKay WR, Apfel CC. Effect of increased body mass index and anaesthetic duration on recovery of protective airway reflexes after sevoflurane vs desflurane. Br J Anaesth. 2010 Feb;104(2):175-82. doi: 10.1093/bja/aep374. Epub 2009 Dec 26.
Background: PubMed 18635478Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268.
Background: PubMed 1449405DePippo KL, Holas MA, Reding MJ. Validation of the 3-oz water swallow test for aspiration following stroke. Arch Neurol. 1992 Dec;49(12):1259-61. doi: 10.1001/archneur.1992.00530360057018.

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.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 6 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 16 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 8 May 2014). 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?

Recovery of Ability to Swallow After Neostigmine/Glycopyrrolate Antagonism of Rocuronium Paralysis. (time frame: At 2 minutes after response to command (T1).). 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 NCT01199237, which also lists 6 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 16 May 2014.