Anaesthetics Gases, XenonPhase 4XABPNCT00793663
Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia
A Phase 4 study testing Xenon, Sevoflurane and Dexamethasone in people with Anaesthetics Gases, Xenon and Anaesthetics Volatile, Sevoflurane, run by RWTH Aachen University at 1 site in Germany.
Trial summary
The purpose of this study is ad 1) to measure the depth of hypnosis as assessed by BIS and cAAI during an average general anesthesia with xenon or sevoflurane and to establish a reliable monitoring system for measuring and documenting the actual depth of hypnosis for the volatile anesthetics investigated. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Anaesthetics Gases, Xenon, Anaesthetics Volatile, Sevoflurane, Depth of Anaesthesia
- What is being tested?
- Xenon, Sevoflurane and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2008to Apr 2011
- 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
- patients ≥ 18 < 75 years
- ASA physical status I-II
- planned duration of anesthesia ≥ 60 minutes
- Apfel score ≥ 2-3
- elective (laparoscopic) surgery (abdominal, gynecological)
- women: with a highly effective contraception, defined as methods with a pearl index < 1 (i.e. hormonal contraceptives, IUD)
Who cannot join
- history of hypersensitivity to any used drugs or additive components used for preparation and stabilization of the named drugs in this trial
- history or reasonable suspicion of malignant hyperthermia and/or degenerative neuromuscular disease, in the subject observed or blood relatives
- history of liver function disorders, leucocytosis and unclear fever after usage of halogenated anesthetics.
- any indisposition that may be aggravated by the use of the drugs investigated:
- liver and/or kidney function disorders
- severe acute or chronic infectious disease (i.e. viral, bacterial, fungal)
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- elevated intracranial pressure
- history of gastrointestinal ulcer(s) or inflammatory bowel disease
- severe metabolic disorders
- hematoporphyria
- glaucoma
- hearing disorders
- any disease including air-filled closed cavities, such as pneumothorax, ileus
- pregnancy and lactation period
- subjects under the age of 18 years
- ambulatory surgery
- any disease that is associated with the requirement of a high oxygen yield and/or
- risk of high oxygen consumption:
- severe lung and/or airway disease
- coronary heart disease and/or seriously impaired cardiac function
- severe psychiatric disorder
Trial locations and contacts
1 site in 1 country.
Germany1 site
RWTH Aachen University; Department of Anesthesiology
Aachen, D-52074
About this study
Official title: 1) The Effect of Xenon and Sevoflurane on Hypnosis Monitors. 2) Prevention of Postoperative Nausea and Vomiting. 3) Rescue Treatment of Established Postoperative Nausea and Vomiting. Sevoflurane.
The purpose of this study is ad 1) to measure the depth of hypnosis as assessed by BIS and cAAI during an average general anesthesia with xenon or sevoflurane and to establish a reliable monitoring system for measuring and documenting the actual depth of hypnosis for the volatile anesthetics investigated. Ad 2) the question is to be answered whether 4 mg dexamethasone i.v. is an effective prophylactic treatment against postoperative nausea and vomiting in case of xenon or sevoflurane anesthesia. Ad 3) it serves to gain evidence about the (non-)effectiveness and kinetics of ondansetron as antiemetic remedy after xenon or sevoflurane anesthesia.
Read the detailed description
- Patients included into the trial will randomly be allocated to either 0.8-1.1 minimum alveolar concentration (MAC) xenon in 30 % oxygen or 0.8-1.1 MAC sevoflurane (age adapted)/30 % oxygen. The MAC is defined and will therefore be applied according to the investigated subject's age. Premedication will be performed with midazolam 7.5 mg orally 45 min before induction (standard dose and application form for adults as clinical practice of our department). Anesthesia will be induced in both groups with propofol 2 mg/kg i.v. and remifentanil 0.5 mcg/kg/min by infusion over 60 s. For tracheal intubation non-depolarizing neuromuscular blocking agents can be used (rocuronium 0.6 mg/kg). Both groups will receive remifentanil at a base rate of 0.2 mcg/kg/min. Xenon or sevoflurane can be titrated in the range from 0.8-1.1 MAC according to clinical needs based on the patient's hemodynamic, autonomic and somatic signs. Twenty minutes before the estimated cessation of all surgical procedures 0.05 mg kg-1 piritramide for post anesthetic pain management will be administered intravenously, as well as a short infusion of metamizole 15 mg kg-1. Depth of anesthesia (hypnosis) will be monitored with spontaneous EEG (BIS VISTA, Aspect Medical Systems, Newton, MA) and the mid latency auditory evoked potentials including a monitoring variable indicating the patients hypnotic state calculated from the MLAEP and the electroencephalogram, the composite A-Line ARX Index (cAAI) with the AEP Monitor/2 (Danmeter A/S, Odense, Denmark). Dosing will be conducted according to the current clinical standard without the monitoring, thus the anesthesia provider will be blinded towards both measurements.
- After induction of anesthesia patients will be randomized to a second factor, i.e. 4 mg dexamethasone or placebo for the prevention of PONV. To avoid potential imbalances, this will be achieved using a factorial design. The application of dexamethasone or placebo will be blinded to the investigator assessing postoperative nausea and vomiting.
- Patients who experience significant nausea will be randomized to receive either 4 mg ondansetron or placebo and the course of nausea will be assessed for > 32 min. Again, the application of ondansetron or placebo will be blinded to the investigator assessing postoperative nausea and vomiting. If the symptoms of postoperative nausea and vomiting persist for more than 32 min after treatment additional rescue treatment will be offered. Of note, all patients are able to receive further rescue treatment at any time point of the study on demand.
- Conditions
- Anaesthetics Gases, Xenon, Anaesthetics Volatile, Sevoflurane, Depth of Anaesthesia, Postoperative Nausea, Postoperative Vomiting
- Being tested
- Xenon, Sevoflurane, Dexamethasone, NaCl, Ondansetron
- Keywords
- Xenon, Sevoflurane, Postoperative Nausea and vomiting, Depth of anaesthesia
- Medical subject headings
- Postoperative Nausea and Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XenonDrug
Also called LENOXe
Inhalational gas; maximum dose allowed: 70 % Xenon; the duration of the treatment will be defined through anesthesia-time.
SevofluraneDrug
Also called Sevorane
Inhalation gas; age adapted MAC-values; the duration of the treatment will be defined through anesthesia-time
DexamethasoneDrug
Also called Fortecortin Inject
Intravenous use, 4 mg, single shot
NaClDrug
Intravenous use; single shot
OndansetronDrug
Also called Zofran
Intravenous use; 4 mg; single shot
NaClDrug
Intravenous use; single shot
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | The effect of xenon as an anaesthetic on the depth of hypnosis. Receives: Drug: Xenon |
| 2 | Active comparator | The effect of sevoflurane as an anesthetic on the depth of hypnosis Receives: Drug: Sevoflurane |
| 3 | Experimental | Dexamethasone as prevention of postoperative nausea and vomiting after xenon or sevoflurane anesthesia Receives: Drug: Dexamethasone |
| 4 | Placebo comparator | Not described Receives: Drug: NaCl |
| 5 | Experimental | Ondansetron, to determine the onset-time of ondansetron when used as rescue medication for postoperative nausea and vomiting Receives: Drug: Ondansetron |
| 6 | Placebo comparator | Not described Receives: Drug: NaCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure.
Measured: During anaesthesia
Postoperative nausea as assessed by a verbal rating scale (VRS) ranging between 0 and 10.
Measured: After anesthesia at 5, 10, 15, 30, 45, 60, and 90 min. At 2, 6 and 24 h after anesthesia the maximum nausea will be rated for the 30-120 min, 2-6 h, and 6-24 h interval.
Reduction of VRS nausea immediately at 2, 5, 7.5, 10, 15, 20 and 30 min after rescue treatment administration.
Measured: Maximum nausea will be rated at 2, 6 and 24 hours after treatment for the 30-120 min, 2-6 h and 6-24 h interval.
Secondary outcomes (7)
Heart rate and blood pressure
Measured: During anesthesia
Observer´s assessment of alertness and sedation scales
Measured: Recovery from anesthesia
Sensitivity and specificity characteristics for both the BIS and the cAAI.
Measured: During anesthesia
Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia.
Measured: 24 hours after anaesthesia
Occurrence of postoperative vomiting and the respective time-points will be recorded. Postoperative vomiting is defined as vomiting or retching.
Measured: 24 hours postoperative
Usage of rescue medication, time and dosage
Measured: 24 hours postoperative
Time to discharge from post anesthetic care unit (Aldrete Score ≥ 9 equals the hypothetic discharge time from post anesthetic care unit)
Measured: Time in the post anesthetic care unit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anaesthetics Gases, XenonStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Collaborators
- Air Liquide Santé International
- Investigators
- Rolf Rossaint, MD, Study chair, RWTH University Aachen; Department of Anesthesiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00793663
- Sponsor's protocol ID
- ALS-8-08-A-401
- Other IDs
- EudraCT-number:, 2008-004132-20, Protocol version:, Version V3; Date: 20.10.2008, 2008
- Acronym
- XABP
- Status last verified
- May 2011
- First submitted
- 18 Nov 2008
- Last updated
- 17 May 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Fahlenkamp AV, Stoppe C, Cremer J, Biener IA, Peters D, Leuchter R, Eisert A, Apfel CC, Rossaint R, Coburn M. Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial. PLoS One. 2016 Apr 25;11(4):e0153807. doi: 10.1371/journal.pone.0153807. eCollection 2016.
PubMed 27111335
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1) The Effect of Xenon and Sevoflurane on Hypnosis Monitors. 2) Prevention of Postoperative Nausea and Vomiting. 3) Rescue Treatment of Established Postoperative Nausea and Vomiting. Sevoflurane.
- ClinicalTrials.gov ID
- NCT00793663
- Acronym / sponsor ID
- XABP / ALS-8-08-A-401
- Conditions
- Anaesthetics Gases, Xenon, Anaesthetics Volatile, Sevoflurane, Depth of Anaesthesia, Postoperative Nausea, Postoperative Vomiting
- Keywords
- Xenon, Sevoflurane, Postoperative Nausea and vomiting, Depth of anaesthesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Collaborators
- Air Liquide Santé International
- Study start
- Nov 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 19 Nov 2008 (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.
The purpose of this study is ad 1) to measure the depth of hypnosis as assessed by BIS and cAAI during an average general anesthesia with xenon or sevoflurane and to establish a reliable monitoring system for measuring and documenting the actual depth of hypnosis for the volatile anesthetics investigated. Ad 2) the question is to be answered whether 4 mg dexamethasone i.v. is an effective prophylactic treatment against postoperative nausea and vomiting in case of xenon or sevoflurane anesthesia. Ad 3) it serves to gain evidence about the (non-)effectiveness and kinetics of ondansetron as antiemetic remedy after xenon or sevoflurane anesthesia.
Detailed description
- Patients included into the trial will randomly be allocated to either 0.8-1.1 minimum alveolar concentration (MAC) xenon in 30 % oxygen or 0.8-1.1 MAC sevoflurane (age adapted)/30 % oxygen. The MAC is defined and will therefore be applied according to the investigated subject's age. Premedication will be performed with midazolam 7.5 mg orally 45 min before induction (standard dose and application form for adults as clinical practice of our department). Anesthesia will be induced in both groups with propofol 2 mg/kg i.v. and remifentanil 0.5 mcg/kg/min by infusion over 60 s. For tracheal intubation non-depolarizing neuromuscular blocking agents can be used (rocuronium 0.6 mg/kg). Both groups will receive remifentanil at a base rate of 0.2 mcg/kg/min. Xenon or sevoflurane can be titrated in the range from 0.8-1.1 MAC according to clinical needs based on the patient's hemodynamic, autonomic and somatic signs. Twenty minutes before the estimated cessation of all surgical procedures 0.05 mg kg-1 piritramide for post anesthetic pain management will be administered intravenously, as well as a short infusion of metamizole 15 mg kg-1. Depth of anesthesia (hypnosis) will be monitored with spontaneous EEG (BIS VISTA, Aspect Medical Systems, Newton, MA) and the mid latency auditory evoked potentials including a monitoring variable indicating the patients hypnotic state calculated from the MLAEP and the electroencephalogram, the composite A-Line ARX Index (cAAI) with the AEP Monitor/2 (Danmeter A/S, Odense, Denmark). Dosing will be conducted according to the current clinical standard without the monitoring, thus the anesthesia provider will be blinded towards both measurements.
- After induction of anesthesia patients will be randomized to a second factor, i.e. 4 mg dexamethasone or placebo for the prevention of PONV. To avoid potential imbalances, this will be achieved using a factorial design. The application of dexamethasone or placebo will be blinded to the investigator assessing postoperative nausea and vomiting.
- Patients who experience significant nausea will be randomized to receive either 4 mg ondansetron or placebo and the course of nausea will be assessed for > 32 min. Again, the application of ondansetron or placebo will be blinded to the investigator assessing postoperative nausea and vomiting. If the symptoms of postoperative nausea and vomiting persist for more than 32 min after treatment additional rescue treatment will be offered. Of note, all patients are able to receive further rescue treatment at any time point of the study on demand.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: XenonThe effect of xenon as an anaesthetic on the depth of hypnosis. |
| 2 | Active comparator | Drug: SevofluraneThe effect of sevoflurane as an anesthetic on the depth of hypnosis |
| 3 | Experimental | Drug: DexamethasoneDexamethasone as prevention of postoperative nausea and vomiting after xenon or sevoflurane anesthesia |
| 4 | Placebo comparator | Drug: NaCl |
| 5 | Experimental | Drug: OndansetronOndansetron, to determine the onset-time of ondansetron when used as rescue medication for postoperative nausea and vomiting |
| 6 | Placebo comparator | Drug: NaCl |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- patients ≥ 18 < 75 years
- ASA physical status I-II
- planned duration of anesthesia ≥ 60 minutes
- Apfel score ≥ 2-3
- elective (laparoscopic) surgery (abdominal, gynecological)
Key exclusion criteria (21 listed)
- history of hypersensitivity to any used drugs or additive components used for preparation and stabilization of the named drugs in this trial
- history or reasonable suspicion of malignant hyperthermia and/or degenerative neuromuscular disease, in the subject observed or blood relatives
- history of liver function disorders, leucocytosis and unclear fever after usage of halogenated anesthetics.
- any indisposition that may be aggravated by the use of the drugs investigated:
- liver and/or kidney function disorders
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 |
|---|---|---|
| XenonAlso: LENOXeInhalational gas; maximum dose allowed: 70 % Xenon; the duration of the treatment will be defined through anesthesia-time. | Drug | 1 |
| SevofluraneAlso: SevoraneInhalation gas; age adapted MAC-values; the duration of the treatment will be defined through anesthesia-time | Drug | 2 |
| DexamethasoneAlso: Fortecortin InjectIntravenous use, 4 mg, single shot | Drug | 3 |
| NaClIntravenous use; single shot | Drug | 4 |
| OndansetronAlso: ZofranIntravenous use; 4 mg; single shot | Drug | 5 |
| NaClIntravenous use; single shot | Drug | 6 |
Primary outcome
The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure.
Time frame: During anaesthesia
Postoperative nausea as assessed by a verbal rating scale (VRS) ranging between 0 and 10.
Time frame: After anesthesia at 5, 10, 15, 30, 45, 60, and 90 min. At 2, 6 and 24 h after anesthesia the maximum nausea will be rated for the 30-120 min, 2-6 h, and 6-24 h interval.
Reduction of VRS nausea immediately at 2, 5, 7.5, 10, 15, 20 and 30 min after rescue treatment administration.
Time frame: Maximum nausea will be rated at 2, 6 and 24 hours after treatment for the 30-120 min, 2-6 h and 6-24 h interval.
7 secondary outcomes
Heart rate and blood pressure
Time frame: During anesthesia
Observer´s assessment of alertness and sedation scales
Time frame: Recovery from anesthesia
Sensitivity and specificity characteristics for both the BIS and the cAAI.
Time frame: During anesthesia
Awareness after anesthesia assessed by the Brice questionnaire at 2 and 24 hours after anesthesia.
Time frame: 24 hours after anaesthesia
Occurrence of postoperative vomiting and the respective time-points will be recorded. Postoperative vomiting is defined as vomiting or retching.
Time frame: 24 hours postoperative
Usage of rescue medication, time and dosage
Time frame: 24 hours postoperative
Time to discharge from post anesthetic care unit (Aldrete Score ≥ 9 equals the hypothetic discharge time from post anesthetic care unit)
Time frame: Time in the post anesthetic care unit
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 17 May 2011.
- Derived from this study: PubMed 27111335Fahlenkamp AV, Stoppe C, Cremer J, Biener IA, Peters D, Leuchter R, Eisert A, Apfel CC, Rossaint R, Coburn M. Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial. PLoS One. 2016 Apr 25;11(4):e0153807. doi: 10.1371/journal.pone.0153807. eCollection 2016.
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.
Rolf Rossaint, MD study chair
RWTH University Aachen; Department of Anesthesiology
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 Xenon, Sevoflurane and Dexamethasone in people with Anaesthetics Gases, Xenon and Anaesthetics Volatile, Sevoflurane, run by RWTH Aachen University at 1 site in Germany.
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 21 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 17 May 2011. 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 Germany. 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. Some participants in this study may receive a placebo. 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?
The average depths of hypnosis as assessed by the BIS and the cAAI between skin incision and start of closure. (time frame: During anaesthesia). The study lists 3 primary outcomes in all. 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 NCT00793663, 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 17 May 2011.