Respiratory DepressionPhase 1(OIRD)NCT02473354
Predictors of Opioid-Induced Respiratory Depression (OIRD)
A Phase 1 study testing Remifentanil, Oxygen and Carbon dioxide in people with Respiratory Depression, run by Duke University at 1 site in United States.
Trial summary
Purpose of the Study: (1) To classify an individual subject's ventilatory response in terms of respiratory depression to a bolus of remifentanil under normoxic and hyperoxic conditions. (2) Measurement of specific respiratory parameters to predict the opioid-induced respiratory depression (OIRD) response. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Respiratory Depression
- What is being tested?
- Remifentanil, Oxygen and Carbon dioxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 29 Apr 2018
- Phase
- Phase 1
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- is between 18 and 50 years of age;
- weighs greater than 40 kilograms;
- is American Society Anesthesiologist (ASA) status 1 [assessment by PI or delegate];
- has a BMI between 18.0 and 30.0 [calculated from measured height \& weight];
- has completed the appropriate fasting periods for solids and liquids prior to the administration of remifentanil
- and has provided written informed consent and is willing to comply with the study procedures.
Who cannot join
- has a prior or known allergy to lidocaine or similar pharmacologic agents;
- is currently taking any medication other than for birth control;
- is currently participating in, or has recently participated in (discontinued within 30 days prior to this study) in an investigational drug study [self-reported];
- has a negative Allen's Test to confirm patency of the collateral artery [clinical assessment by PI or delegate];
- has made a whole blood donation or has had at least 450 ml of blood drawn within 8 weeks prior to the study procedure [self-reported];
- is female with a positive pregnancy test [serum or urine], or is female and is unwilling to use effective birth control between the time of screening and study procedure;
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- has anemia [measured by venous blood gas sample];
- has a history of sickle cell disease [self-reported];
- has a positive urine cotinine or urine drug screen or oral ethanol test [POC testing];
- has a history of narcotic or recreational drug addition [self reported by subject in response to questioning by PI or delegate; review of duke electronic medical history record];
- has room air saturation less than 95% by pulse oximetry [measurement by PI or delegate];
- has a clinically significant abnormal EKG [assessment by PI or delegate];
- has a clinically significant abnormal pulmonary function test via spirometry [assessment by PI or delegate];
- has a COHb greater than 3%, or MetHb greater than 2% [measured by venous blood sample co-oximetry];
- is intolerant to a breathing mask apparatus [assessment by PI or delegate];
- has any condition in the opinion of the investigator which would make him or her unsuitable for study participation [assessment by PI or delegate];
- is unwilling or unable to provide informed consent or comply with the study procedures;
- has Rayanud's disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health Systems
Durham, North Carolina, 27710
About this study
Purpose of the Study: (1) To classify an individual subject's ventilatory response in terms of respiratory depression to a bolus of remifentanil under normoxic and hyperoxic conditions. (2) Measurement of specific respiratory parameters to predict the opioid-induced respiratory depression (OIRD) response.
Read the detailed description
This study is using FDA approved drugs (remifentanil, oxygen and carbon dioxide) in an investigational manner and the study is also developing a diagnostic test that is currently investigational. Investigational means that the FDA has not approved the use of the drugs in this manner or the diagnostic test being developed.
Opioid-Induced Respiratory Depression (OIRD) is recognized as potentially life threatening and the cause of substantial morbidity (poor health) and mortality (death). Respiratory depression is when the amount of breathing you do in a minute falls below normal. Opioids are medications widely used to treat both acute (lasting hours to days) and chronic (lasting months) pain, both within and outside the hospital setting. Opioids have been used outside the prescribed circumstances resulting in misuse and abuse. Even within the controlled environment of acute hospital care it is difficult to identify those individuals at most risk of OIRD, as many do not possess physical characteristics, such as obesity or obstructive sleep apnea (stop breathing during sleep), which may predispose to OIRD. In the absence of the ability to easily identify at-risk individuals the Anesthesia Patient Safety Foundation have suggested that all patients receiving opioids must be considered at risk of OIRD and therefore require appropriate monitoring.
Even when fully awake, the normal response to breathing a gas mixture containing carbon dioxide (CO2) is to increase the amount of breathing. The effect is similar to breathing in and out of a paper bag. This is called the Hypercapnic Ventilatory Response (HCVR) and can be measured. Not everyone responds in an identical manner - there will be differences in the HCVR from one person to the next. But if an individual's baseline HCVR is measured, then the change from baseline can also be measured.
This study is being done to: (1) classify or rate an individual subject's ventilatory (breathing) response in terms of respiratory depression to a bolus of a potent opioid (similar to morphine, often referred to as a narcotic). The opioid used for this study is Remifentanil and is commonly used in the operating room. Remifentanil will be given under normoxic (breathing room air [21% Oxygen]) and hyperoxic (breathing 50% oxygen) conditions to (2) determine if the measurement of the specific respiratory parameters will predict the OIRD response.
- Conditions
- Respiratory Depression
- Being tested
- Remifentanil, Oxygen, Carbon dioxide
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemifentanilDrug
The opioid used for this study is Remifentanil and is commonly used in the operating room. Remifentanil will be given under normoxic (breathing room air [21% Oxygen]) and hyperoxic (breathing 50% oxygen) conditions to determine if the measurement of the specific respiratory parameters will predict the OIRD response.
OxygenDrug
Also called O2
Remifentanil will be administered under normal oxygen (normoxia) and increased oxygen (hyperemic) conditions.
Carbon dioxideDrug
Also called CO2
Carbon dioxide is used as part of the hypercapnia ventilatory response measurement (HCVR)
| Study group | Role | What they receive |
|---|---|---|
| Resp Depression Sequence 1 - 3 | Other | Sequence #1: breathe 21% through the facemask and increase ventilation to achieve a target hypocapnic ET CO2 of 25 - 30 mmHg. Subject will then breathe a gas mixture containing 6% CO2 / 30% O2 to achieve a target hypercapnic ET CO2 up to 60 mmHg or HCVR is terminated at the discretion of the PI.
Sequence #2: breathe 21% O2 (normoxia) before remifentanil administration Sequence #3: breathe 50% O2 (hyperoxia) before remifentanil administration Receives: Drug: Remifentanil; Drug: Oxygen; Drug: Carbon dioxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypercapnic Ventilatory Response (HCVR) gradient based upon ETCO2 and Minute Volume
Is there a correlation between the HCVR and susceptibility of OIRD.
Measured: Sequence #1 approximately 30 minutes
Secondary outcomes (1)
The proportion of subjects who are classified as low, medium, or high risk for Opioid Induced Respiratory Depression (OIRD).
This will be measure in Low, Medium, or High.
Measured: Sequence #2 approximately 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2015 (estimated)
- Study startApr 2015
- Primary completion29 Apr 2018
- Study completion29 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory DepressionStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 1
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David MacLeod, MB BS, Principal investigator, Duke Anesthesiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02473354
- Sponsor's protocol ID
- Pro00060429
- Acronym
- (OIRD)
- Status last verified
- Mar 2020
- First submitted
- 3 Jun 2015
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictors of Opioid-Induced Respiratory Depression (OIRD)
- ClinicalTrials.gov ID
- NCT02473354
- Acronym / sponsor ID
- (OIRD) / Pro00060429
- Conditions
- Respiratory Depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- 29 Apr 2018 (actual)
- Study completion
- 29 Apr 2018 (actual)
- First posted
- 16 Jun 2015 (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.
Purpose of the Study: (1) To classify an individual subject's ventilatory response in terms of respiratory depression to a bolus of remifentanil under normoxic and hyperoxic conditions. (2) Measurement of specific respiratory parameters to predict the opioid-induced respiratory depression (OIRD) response.
Detailed description
This study is using FDA approved drugs (remifentanil, oxygen and carbon dioxide) in an investigational manner and the study is also developing a diagnostic test that is currently investigational. Investigational means that the FDA has not approved the use of the drugs in this manner or the diagnostic test being developed.
Opioid-Induced Respiratory Depression (OIRD) is recognized as potentially life threatening and the cause of substantial morbidity (poor health) and mortality (death). Respiratory depression is when the amount of breathing you do in a minute falls below normal. Opioids are medications widely used to treat both acute (lasting hours to days) and chronic (lasting months) pain, both within and outside the hospital setting. Opioids have been used outside the prescribed circumstances resulting in misuse and abuse. Even within the controlled environment of acute hospital care it is difficult to identify those individuals at most risk of OIRD, as many do not possess physical characteristics, such as obesity or obstructive sleep apnea (stop breathing during sleep), which may predispose to OIRD. In the absence of the ability to easily identify at-risk individuals the Anesthesia Patient Safety Foundation have suggested that all patients receiving opioids must be considered at risk of OIRD and therefore require appropriate monitoring.
Even when fully awake, the normal response to breathing a gas mixture containing carbon dioxide (CO2) is to increase the amount of breathing. The effect is similar to breathing in and out of a paper bag. This is called the Hypercapnic Ventilatory Response (HCVR) and can be measured. Not everyone responds in an identical manner - there will be differences in the HCVR from one person to the next. But if an individual's baseline HCVR is measured, then the change from baseline can also be measured.
This study is being done to: (1) classify or rate an individual subject's ventilatory (breathing) response in terms of respiratory depression to a bolus of a potent opioid (similar to morphine, often referred to as a narcotic). The opioid used for this study is Remifentanil and is commonly used in the operating room. Remifentanil will be given under normoxic (breathing room air [21% Oxygen]) and hyperoxic (breathing 50% oxygen) conditions to (2) determine if the measurement of the specific respiratory parameters will predict the OIRD response.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Resp Depression Sequence 1 - 3 | Other | Drug: Remifentanil, Drug: Oxygen, Drug: Carbon dioxideSequence #1: breathe 21% through the facemask and increase ventilation to achieve a target hypocapnic ET CO2 of 25 - 30 mmHg. Subject will then breathe a gas mixture containing 6% CO2 / 30% O2 to achieve a target hypercapnic ET CO2 up to 60 mmHg or HCVR is terminated at the discretion of the PI. Sequence #2: breathe 21% O2 (normoxia) before remifentanil administration Sequence #3: breathe 50% O2 (hyperoxia) before remifentanil administration |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- is between 18 and 50 years of age;
- weighs greater than 40 kilograms;
- is American Society Anesthesiologist (ASA) status 1 [assessment by PI or delegate];
- has a BMI between 18.0 and 30.0 [calculated from measured height \& weight];
- has completed the appropriate fasting periods for solids and liquids prior to the administration of remifentanil
Key exclusion criteria (18 listed)
- has a prior or known allergy to lidocaine or similar pharmacologic agents;
- is currently taking any medication other than for birth control;
- is currently participating in, or has recently participated in (discontinued within 30 days prior to this study) in an investigational drug study [self-reported];
- has a negative Allen's Test to confirm patency of the collateral artery [clinical assessment by PI or delegate];
- has made a whole blood donation or has had at least 450 ml of blood drawn within 8 weeks prior to the study procedure [self-reported];
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 |
|---|---|---|
| RemifentanilThe opioid used for this study is Remifentanil and is commonly used in the operating room. Remifentanil will be given under normoxic (breathing room air [21% Oxygen]) and hyperoxic (breathing 50% oxygen) conditions to determine if the measurement of the specific respiratory parameters will predict the OIRD response. | Drug | Resp Depression Sequence 1 - 3 |
| OxygenAlso: O2Remifentanil will be administered under normal oxygen (normoxia) and increased oxygen (hyperemic) conditions. | Drug | Resp Depression Sequence 1 - 3 |
| Carbon dioxideAlso: CO2Carbon dioxide is used as part of the hypercapnia ventilatory response measurement (HCVR) | Drug | Resp Depression Sequence 1 - 3 |
Primary outcome
Hypercapnic Ventilatory Response (HCVR) gradient based upon ETCO2 and Minute Volume
Time frame: Sequence #1 approximately 30 minutes
Is there a correlation between the HCVR and susceptibility of OIRD.
1 secondary outcome
The proportion of subjects who are classified as low, medium, or high risk for Opioid Induced Respiratory Depression (OIRD).
Time frame: Sequence #2 approximately 1 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 10 Mar 2020.
- Individual participant dataSharing planned: Undecided
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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.
David MacLeod, MB BS principal investigator
Duke Anesthesiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Remifentanil, Oxygen and Carbon dioxide in people with Respiratory Depression, run by Duke University at 1 site in United States.
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 18 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 10 Mar 2020. 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 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Hypercapnic Ventilatory Response (HCVR) gradient based upon ETCO2 and Minute Volume (time frame: Sequence #1 approximately 30 minutes). 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 10 Mar 2020; AzTrials last refreshed its copy on 7 Nov 2026.