Effect on ventilatory pattern with an opioid under fake postsurgical conditions in men and women
| ISRCTN | ISRCTN12454921 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12454921 |
| EudraCT/CTIS number | 2023-508915-22-00 |
| Secondary identifying numbers | P23.097 |
- Submission date
- 16/01/2024
- Registration date
- 21/05/2024
- Last edited
- 21/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
While it is well known that an opioid overdose produces immediate respiratory depression, the effect of surgical doses of opioids on the postoperative ventilatory pattern. One large study, the PRODIGY study, claimed that about half of all postoperative patients on opioids for pain relief will experience at least one apnea event (no breathing for at least 30 s). However, we remain uninformed whether this is truly opioid related as ventilatory pattern under control conditions was not tested and there may be effects from other drugs as well. Here we will mimic surgical administration of the opioid fentanyl and will measure the ventilatory pattern during and following sham surgery.
The objective is to explore the ventilatory pattern of volunteers during and following administration of fentanyl, mimicking the perioperative dosing of fentanyl
Who can participate?
12 healthy volunteers (6 men/6 women), aged 18-45 years, with a body mass index of 19-30 kg/m².
What does the study involve?
We're going to simulate the administration of fentanyl during a fake surgery that lasts 150 minutes. We'll be giving doses of fentanyl every 30 minutes and monitoring how much air a person breathes in and out for each breath, starting from when we give the first dose until 90 minutes after the fake surgery ends. Only fentanyl will be used, with no other drugs.
Here's the breakdown of the fentanyl doses:
1. At the beginning of the simulation, we'll give 100 micrograms of fentanyl through an IV.
2. Then, at 30 and 60 minutes into the fake surgery, we'll administer 75 micrograms of fentanyl each time.
3. At 90 and 120 minutes into the fake surgery, we'll give a reduced dose of 50 micrograms of fentanyl.
This method allows us to observe how the increasing amounts of fentanyl affect the way the person breathes. The doses gradually increase from 150 to 250 micrograms at 60 minutes and then to 350 micrograms at 120 minutes into the fake surgery.
After that, we'll continue monitoring the person's breathing until 90 minutes after the fake surgery concludes. The entire process, including the surgery simulation and the follow-up, will take 240 minutes (4 hours). It's important to note that all the mentioned doses are calculated based on a total body weight of 70 kilograms.
What are the possible benefits and risks of participating?
These volunteers in this experimental trial will not gain any medical benefit from the study. The benefit lies within the gained knowledge in our ability to understand and consequently treat, reverse and prevent opioid-induced respiratory depression in perioperative patients.
The burden of the study is related to the measurements and interventions. However, the burden and risk are contained in the highly controlled setting. The investigators have ample experience, most are anesthesiologists, and have performed multiple similar protocols without any inflicted harm or long-term effects to the participants. The subjects will receive an appropriate yet modest reimbursement for their participation.
Where is the study run from?
Leiden University Medical Center (Netherlands)
When is the study starting and how long is it expected to run for?
October 2023 to January 2025
Who is funding the study?
Leiden University Medical Center (Netherlands)
Who is the main contact?
Prof. Albert Dahan, a.dahan@lumc.nl
Contact information
Public, Scientific, Principal Investigator
Albinusdreef 2
Leiden
2333 ZA
Netherlands
 ORCID ID |
0000-0003-3161-3945 |
|---|---|
| a.dahan@lumc.nl |
Study information
| Study design | Open-label exploratory observational design |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Safety |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Fentanyl effect on ventilatory pattern under sham postsurgical conditions – an exploratory study in healthy men and women |
| Study acronym | FAME |
| Study objectives | While it is well known that an opioid overdose produces immediate respiratory depression, the effect of surgical doses of opioids on the postoperative ventilatory pattern. One large study, the PRODIGY study, claimed that about half of all postoperative patients on opioids for pain relief will experience at least one apnea event (no breathing for at least 30 s). However, we remain uninformed whether this is truly opioid related as ventilatory pattern under control conditions was not tested and there may be effects from other drugs as well. Here we will mimic surgical administration of the opioid fentanyl and will measure the ventilatory pattern during and following sham surgery. The objective is to explore the ventilatory pattern of volunteers during and following administration of fentanyl, mimicking the perioperative dosing of fentanyl. |
| Ethics approval(s) |
Approved 15/01/2024, METC-LDD (Albinusdreef 2, Leiden, 2333ZA, Netherlands; +31 0071-5263241; metc-ldd@lumc.nl), ref: P23.097 |
| Health condition(s) or problem(s) studied | Fentanyl effect on ventilatory pattern under sham postsurgical conditions |
| Intervention | We will mimic fentanyl dosing for a 150 min sham surgical procedure. We will dose fentanyl at 30 min interval and measure minute ventilation on a breath-to-breath basis from the start of administration until 90 min after sham surgery. We will administer just fentanyl without any other drugs. Upon induction we will give 100 μg fentanyl intravenously, followed by 75 μg at t = 30 and 60 min of surgery and 50 μg at 90 and 120 min of surgery. This approach allows the detecting of escalating doses of fentanyl on the ventilatory pattern. The dose increases from 150 to 250 μg at t = 60 min to 350 at t = 120 min of surgery. We will next continue measuring ventilation until t = 90 min after surgery. Total duration is 150 min of surgery + 90 min follow-up = 240 min (4 h) of breath-to-breath data. All doses are per 70 kg total body weight. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic |
| Phase | Phase III/IV |
| Drug / device / biological / vaccine name(s) | Fentanyl |
| Primary outcome measure | Arterial PCO2 in the recovery phase (last 90 min of the study) measured using arterial blood gas at specific time points in the recovery phase |
| Secondary outcome measures | The occurrence of a respiratory event as defined by: 1. Respiratory rate ≤5 breaths/min for ≥ 3 min; 2. Oxygen saturation ≤ 85% for ≥ 3 min; 3. End-tidal PCO2 ≤ 2 kPa or ≥ 8 kPa for ≥ 3 min; 4. Apnea for at least 30 s; 5. Any other respiratory event; all measured using a continuous flowsensor, gas analyzer, and custom made software to identify the respiratory rate 6. The comparison of arterial vs venous vs end-tidal PCO2 measured using the custom made software, gas analyzer and flowsensor in combination with the arterial blood gas with the blood gas analyzer |
| Overall study start date | 01/10/2023 |
| Completion date | 01/01/2025 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Both |
| Target number of participants | 12 |
| Key inclusion criteria | 1. Aged 18-45 years 2. Body mass index 19-30 kg/m² |
| Key exclusion criteria | 1. Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than caffeine, or nicotine- 2. Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints; 3. Pregnancy or lactation; 4. A positive drug urine dipstick on the screening or study days. 5. History or presence of allergic response to study medication; |
| Date of first enrolment | 01/02/2024 |
| Date of final enrolment | 01/01/2025 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Leiden
2333ZA
Netherlands
Sponsor information
Hospital/treatment centre
Albinusdreef 2
Leiden
2333ZA
Netherlands
| a.dahan@lumc.nl | |
| Website | https://www.lumc.nl/?setlanguage=English&setcountry=en |
"ROR" |
https://ror.org/05xvt9f17 |
Funders
Funder type
Hospital/treatment centre
Government organisation / Local government
- Alternative name(s)
- Leiden University Medical Center, LUMC
- Location
- Netherlands
Results and Publications
| Intention to publish date | 01/01/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Editorial Notes
17/01/2024: Trial's existence confirmed by METC-LDD.
