CoughPhase 4REXNCT03132519
Optimal Remifentanil Ce for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation
A Phase 4 study testing Remifentanil in people with Cough and Hypertension, run by Fundacion Clinica Valle del Lili at 1 site in Colombia.
Trial summary
Pain, cough, hypertension and tachycardia are frequent events during extubation due to a secondary stimulation of mechanoreceptors located in the airway. The mechanical effect of the endotracheal tube activates autonomic reflexes, a situation that could potentially impair the clinical condition of patients. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Cough, Hypertension
- What is being tested?
- Remifentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 364 participants
- Where
- 1 siteColombia
- Study dates
- Oct 2013to Feb 2016
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- American Society of Anesthesia status I and II
- Age between 18 to 60 years.
- Elective surgery.
Who cannot join
- Uncontrolled hypertension. (SBP> 180 mmHg) at pre anesthesia area.
- Active or uncontrolled pulmonary disease.
- Signs or history of difficult airway.
- Recent respiratory infection.
- Train-of-four (TOF) index <90% at the end of surgery.
- Patients who have received some form of pre oral medication.
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- Body mass Index above 30 kg/m2.
- Concomitant use of epidural catheter.
- Urgent surgery.
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Fundacion Valle del Lili
Cali, Valle del Cauca Department, 76001000
About this study
Official title: Optimal Remifentanil Site-effect Concentration for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation After Sevoflurane vs. Desflurane. A Randomized Clinical Trial
Pain, cough, hypertension and tachycardia are frequent events during extubation due to a secondary stimulation of mechanoreceptors located in the airway. The mechanical effect of the endotracheal tube activates autonomic reflexes, a situation that could potentially impair the clinical condition of patients. Previous studies have used remifentanil during emergence and extubation showing good results to control this reflex response. However, it is unknown so far, the optimal effect site concentration (Ce) of remifentanil to allow a better control of these events with a low incidence of adverse effects after have received inhaled anesthesia plus remifentanil for anesthetic maintenance. This study will determine the Ce of remifentanil associated with a lower proportion of cough and hyperdynamic circulatory response during extubation for emergency after exposure to sevoflurane or desflurane.
Read the detailed description
Single-center, randomized, double-blind protocol. The investigators aim to include 368 patients under balanced anesthesia with sevoflurane or desflurane to be randomly allocated into 6 different remifentanil Ce groups [77 individuals in each of interventional groups (2.0 vs. 2.5 ng/ml) and 30 in each of the control groups (1.0 ng/ml) administrated by a target-controlled infusion (TCI) system during emergence and tracheal extubation .
Once informed consent is obtained and inclusion/exclusion criteria are met, subjects will be randomized before starting of the surgical procedure. This information will remain blinded to the attendant anesthesiologist and the independent evaluator during the process of extubation, except for type of inhaled anesthetic for maintenance .
The intervention will start when the anesthesiologist decide to suspend the sevorane or desflurane dial. At this moment, the fresh flow gas of the anesthesia machine will be adjusted to 7-8 liters per minute and the infusion of remifentanil will be set up to establish a Ce of 2.0 ng/ml or 2.5 ng/ml. All patients will be extubated only when all of these three parameters exist: response to name by eyes opening, response to orders of breathing and mouth opening.
The evaluation and outcomes measurement will include: Presence and intensity of cough and changes in heart rate and blood pressure during eyes opening in response to calling by name, tracheal extubation and 2.5 min after, time to get to be extubated after inhaled anesthetic discontinuation, episodes of hypoxemia and sedation state during the first 25 minutes after extubation, requirements of rescue analgesia and postoperative nausea and vomit during this period.
Close monitoring of patients will take place and data will be collected during the preoperative, intraoperative and postoperative stages until discharge from the post anesthesia care unit. Lost to follow and adverse events will be assessed. An interim committee will evaluate partial results of the study when it reaches 25 and 50% of recruitment, so the investigators can continue building thereof according to analysis obtained.
Statistical analysis will be performed by a independent statistician based on "intention to treat" principle. In addition, excluded data and its reasons for exclusion will be evaluated. For the descriptive exploratory analysis, continuous variables will be presented as means (standard deviation) or medians (interquartile ranges). The degree of dispersion, shape and position as the fulfillment of normality will be analyzed using the t of Student or Mann-Whitney tests as appropriate. Categorical variables will be presented as proportions and compared using the chi-square or Fisher 's exact tests as appropriate. Time-varying measures analysis of variance for repeated measures will be used to make comparisons between groups.
- Conditions
- Cough, Hypertension
- Being tested
- Remifentanil
- Keywords
- Cough, Hypertension, Remifentanil, Sevoflurane, Desflurane
- Medical subject headings
- Cough, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemifentanilDrug
Also called Ultiva
To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation
| Study group | Role | What they receive |
|---|---|---|
| Sevo-2.0 | Experimental | This group will maintain remifentanil infusion by TCI to 2 ng/ml during emergence and extubation after have received sevoflurane during procedure. Receives: Drug: Remifentanil |
| Sevo-2.5 | Experimental | This group will maintain the remifentanil infusion by TCI to 2.5 ng/ml during emergence and tracheal extubation after have received sevoflurane during surgical procedure. Receives: Drug: Remifentanil |
| Des-2.0 | Experimental | This group will maintain the remifentanil infusion by TCI to 2.0 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure. Receives: Drug: Remifentanil |
| Des-2.5 | Experimental | This group will maintain the remifentanil infusion by TCI to 2.5 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure. Receives: Drug: Remifentanil |
| Sevo-Control | Active comparator | This group will maintain the remifentanil infusion by TCI to 1.0 ng/ml during emergence and tracheal extubation after have received sevoflurane during surgical procedure. Receives: Drug: Remifentanil |
| Des-Control | Active comparator | This group will maintain the remifentanil infusion by TCI to 1.0 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure. Receives: Drug: Remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cough during emergency from anesthesia
Assess the presence and intensity of cough : 0) No cough, 1) A single episode of cough, 2) More than one episode of nonsustained cough, 3) sustained and repetitive cough with head elevation.
Measured: From eye opening up to 2.5 minutes after tracheal extubation
Secondary outcomes (9)
Cardiac response during emergence from anesthesia
Assessment of heart rate (bpm) during awakening and tracheal extubation: Measurements of systolic blood pressure will be obtained at the time of suspending of the halogenated (Basal 2) , eye opening, tracheal extubation and 2.5 minutes after extubation
Measured: From discontinuation of inhalational anesthetics up to 2.5 minutes after tracheal extubation
Pressor response during emergence from anesthesia
Assessment of systolic blog pressure (mmHg) during awakening and tracheal extubation: Measurements of systolic blood pressure will be obtained at the time of suspending of the halogenated (Basal 2) , eye opening, tracheal extubation and 2.5 minutes after extubation
Measured: From discontinuation of inhalational anesthetics up to 2.5 minutes post-extubation
Time to eye opening
Time in seconds from inhaled anesthetic discontinuation to eye opening response to call by name and touch stimuli.
Measured: From inhaled anesthetic discontinuation until the moment of eye opening response to verbal command (calling by name), assessed up to 20 minutes.
Time to tracheal extubation
Time in seconds from inhaled anesthetic discontinuation to safety conditions for tracheal extubation (patients must respond positively to three different commands: "open your eyes " , "breath deep " and "open your mouth ")
Measured: From inhaled anesthetic discontinuation until the event of tracheal extubation, assessed up to 20 minutes.
Halogenated end tidal concentration at tracheal extubation
Inhaled gas concentration measured in vol % by the gas analyzer at tracheal extubation
Measured: From eyes opening until the event of tracheal extubation, assessed up to 20 minutes.
Respiratory rate during post-extubation
Number of breaths per minute during spontaneous ventilation.
Measured: From tracheal extubation to 25 minutes later
Post-extubation hypoxemia
Continuous non-invasive measurement of the percentage of hemoglobin that is attached to oxygen through a pulse oximeter . Episodes of arterial oxygen saturation less than 92% , which is present in the next 10 minutes to extubation were recorded and encourage the patient to breathe through call and tactile stimulation as necessary during this time. If you arrived 10 minutes after extubation the patient continues to present desaturation because bradypnea / intermittent apnea the same process will continue until the patient has spontaneous ventilation ( breathing without any verbal or tactile stimulation ) .
Measured: From tracheal extubation to 25 minutes
Rescue analgesia requirement in the immediate postoperative time
Amount of opioid requirements for rescue analgesia during first postoperative hour (other opioids dose will be converted to equipotent milligrams of morphine.
Measured: From tracheal extubation up to first postoperative hour
Postoperative nausea and vomiting
Rated on a scale of 0-3, representing presence and intensity of nausea and / or vomiting within the first postoperative hour 0 = no nausea
- = mild nausea without vomiting episodes
- = nausea and a single episode of vomiting
- = more than one episode of vomiting during the first hour
Measured: From tracheal extubation to first postoperative hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2017
- Study startOct 2013
- Primary completionNov 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CoughStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 364 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion Clinica Valle del Lili
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fredy Ariza, Fundacion Clinica Valle del Lili
- Investigators
- Fredy G Ariza, MD., MSc., Principal investigator, Fundacion Clinica Valle del LiliIvan F Quintero, MD, Study chair, Fundacion Clinica Valle del Lili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03132519
- Sponsor's protocol ID
- REX
- Acronym
- REX
- Status last verified
- Apr 2017
- First submitted
- 25 Apr 2014
- Last updated
- 2 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data available for future validations at institutional database system from Clinical Research Center, Fundación Valle del Lili of
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Remifentanil Site-effect Concentration for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation After Sevoflurane vs. Desflurane. A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03132519
- Acronym / sponsor ID
- REX / REX
- Conditions
- Cough, Hypertension
- Keywords
- Cough, Hypertension, Remifentanil, Sevoflurane, Desflurane
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 364 participants (actual)
- Lead sponsor
- Fundacion Clinica Valle del LiliUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Nov 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 28 Apr 2017 (actual)
- 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.
Pain, cough, hypertension and tachycardia are frequent events during extubation due to a secondary stimulation of mechanoreceptors located in the airway. The mechanical effect of the endotracheal tube activates autonomic reflexes, a situation that could potentially impair the clinical condition of patients. Previous studies have used remifentanil during emergence and extubation showing good results to control this reflex response. However, it is unknown so far, the optimal effect site concentration (Ce) of remifentanil to allow a better control of these events with a low incidence of adverse effects after have received inhaled anesthesia plus remifentanil for anesthetic maintenance. This study will determine the Ce of remifentanil associated with a lower proportion of cough and hyperdynamic circulatory response during extubation for emergency after exposure to sevoflurane or desflurane.
Detailed description
Single-center, randomized, double-blind protocol. The investigators aim to include 368 patients under balanced anesthesia with sevoflurane or desflurane to be randomly allocated into 6 different remifentanil Ce groups [77 individuals in each of interventional groups (2.0 vs. 2.5 ng/ml) and 30 in each of the control groups (1.0 ng/ml) administrated by a target-controlled infusion (TCI) system during emergence and tracheal extubation .
Once informed consent is obtained and inclusion/exclusion criteria are met, subjects will be randomized before starting of the surgical procedure. This information will remain blinded to the attendant anesthesiologist and the independent evaluator during the process of extubation, except for type of inhaled anesthetic for maintenance .
The intervention will start when the anesthesiologist decide to suspend the sevorane or desflurane dial. At this moment, the fresh flow gas of the anesthesia machine will be adjusted to 7-8 liters per minute and the infusion of remifentanil will be set up to establish a Ce of 2.0 ng/ml or 2.5 ng/ml. All patients will be extubated only when all of these three parameters exist: response to name by eyes opening, response to orders of breathing and mouth opening.
The evaluation and outcomes measurement will include: Presence and intensity of cough and changes in heart rate and blood pressure during eyes opening in response to calling by name, tracheal extubation and 2.5 min after, time to get to be extubated after inhaled anesthetic discontinuation, episodes of hypoxemia and sedation state during the first 25 minutes after extubation, requirements of rescue analgesia and postoperative nausea and vomit during this period.
Close monitoring of patients will take place and data will be collected during the preoperative, intraoperative and postoperative stages until discharge from the post anesthesia care unit. Lost to follow and adverse events will be assessed. An interim committee will evaluate partial results of the study when it reaches 25 and 50% of recruitment, so the investigators can continue building thereof according to analysis obtained.
Statistical analysis will be performed by a independent statistician based on "intention to treat" principle. In addition, excluded data and its reasons for exclusion will be evaluated. For the descriptive exploratory analysis, continuous variables will be presented as means (standard deviation) or medians (interquartile ranges). The degree of dispersion, shape and position as the fulfillment of normality will be analyzed using the t of Student or Mann-Whitney tests as appropriate. Categorical variables will be presented as proportions and compared using the chi-square or Fisher 's exact tests as appropriate. Time-varying measures analysis of variance for repeated measures will be used to make comparisons between groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Sevo-2.0 | Experimental | Drug: RemifentanilThis group will maintain remifentanil infusion by TCI to 2 ng/ml during emergence and extubation after have received sevoflurane during procedure. |
| Sevo-2.5 | Experimental | Drug: RemifentanilThis group will maintain the remifentanil infusion by TCI to 2.5 ng/ml during emergence and tracheal extubation after have received sevoflurane during surgical procedure. |
| Des-2.0 | Experimental | Drug: RemifentanilThis group will maintain the remifentanil infusion by TCI to 2.0 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure. |
| Des-2.5 | Experimental | Drug: RemifentanilThis group will maintain the remifentanil infusion by TCI to 2.5 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure. |
| Sevo-Control | Active comparator | Drug: RemifentanilThis group will maintain the remifentanil infusion by TCI to 1.0 ng/ml during emergence and tracheal extubation after have received sevoflurane during surgical procedure. |
| Des-Control | Active comparator | Drug: RemifentanilThis group will maintain the remifentanil infusion by TCI to 1.0 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- American Society of Anesthesia status I and II
- Age between 18 to 60 years.
- Elective surgery.
Key exclusion criteria (9 listed)
- Uncontrolled hypertension. (SBP> 180 mmHg) at pre anesthesia area.
- Active or uncontrolled pulmonary disease.
- Signs or history of difficult airway.
- Recent respiratory infection.
- Train-of-four (TOF) index <90% at the end of surgery.
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 |
|---|---|---|
| RemifentanilAlso: UltivaTo maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation | Drug | Des-2.0, Des-2.5, Des-Control, Sevo-2.0, Sevo-2.5, Sevo-Control |
Primary outcome
Cough during emergency from anesthesia
Time frame: From eye opening up to 2.5 minutes after tracheal extubation
Assess the presence and intensity of cough : 0) No cough, 1) A single episode of cough, 2) More than one episode of nonsustained cough, 3) sustained and repetitive cough with head elevation.
9 secondary outcomes
Cardiac response during emergence from anesthesia
Time frame: From discontinuation of inhalational anesthetics up to 2.5 minutes after tracheal extubation
Pressor response during emergence from anesthesia
Time frame: From discontinuation of inhalational anesthetics up to 2.5 minutes post-extubation
Time to eye opening
Time frame: From inhaled anesthetic discontinuation until the moment of eye opening response to verbal command (calling by name), assessed up to 20 minutes.
Time to tracheal extubation
Time frame: From inhaled anesthetic discontinuation until the event of tracheal extubation, assessed up to 20 minutes.
Halogenated end tidal concentration at tracheal extubation
Time frame: From eyes opening until the event of tracheal extubation, assessed up to 20 minutes.
Respiratory rate during post-extubation
Time frame: From tracheal extubation to 25 minutes later
Post-extubation hypoxemia
Time frame: From tracheal extubation to 25 minutes
Rescue analgesia requirement in the immediate postoperative time
Time frame: From tracheal extubation up to first postoperative hour
Postoperative nausea and vomiting
Time frame: From tracheal extubation to first postoperative 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 2 May 2017.
- Individual participant dataSharing planned: Yes. Data available for future validations at institutional database system from Clinical Research Center, Fundación Valle del Lili of
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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.
Fredy G Ariza, MD., MSc. principal investigator
Fundacion Clinica Valle del Lili
Ivan F Quintero, MD study chair
Fundacion Clinica Valle del Lili
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 Remifentanil in people with Cough and Hypertension, run by Fundacion Clinica Valle del Lili at 1 site in Colombia.
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 9 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 2 May 2017. 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 Colombia. 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?
Cough during emergency from anesthesia (time frame: From eye opening up to 2.5 minutes after tracheal extubation). 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 2 May 2017.