AnesthesiaPhase 3POFANCT03316339
Postoperative and Opioid Free Anesthesia
A Phase 3 study testing Dexmedetomidine and Remifentanil in people with Anesthesia and Opioid-Related Disorders, run by Rennes University Hospital at 11 sites in France.
Trial summary
Since the 1960's, intraoperative administration of opioids is considered a keystone of anesthesia as well as hypnotics and muscle relaxants. Synthetic opioids were introduced to achieve hemodynamic stability during anesthesia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anesthesia, Opioid-Related Disorders
- What is being tested?
- Dexmedetomidine and Remifentanil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 11 sitesFrance
- Study dates
- 29 Nov 2017to 19 Jun 2019
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Undergoing a scheduled major or intermediate non-cardiac surgery,
- Benefiting from the health insurance system,
- Having signed an informed consent.
Who cannot join
- Pregnant or breast feeding women,
- Allergy to dexmedetomidine or one of its excipients,
- Allergy to one of the drugs used for anesthesia or one of their excipients,
- Urgent surgery,
- Intracranial surgery,
- Transplant surgery or transplanted patients,
Show all 19Show fewer
- Surgery with planned regional anesthesia,
- Outpatient surgery,
- Atrioventricular block, intraventricular or sinoatrial block,
- Treatment by chronic betablockers and HR < 50 bpm,
- Heart failure with LVEF < 40%,
- Adam-Stokes syndrome,
- Epilepsy or seizures,
- Uncontrolled hypotension,
- Acute cerebral pathology,
- Obstructive sleep apnea syndrome,
- Severe hepatic insufficiency (Prothrombin Ratio < 15%),
- Patients in whom the CAM-ICU cannot be performed (deaf patients for example)
- Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
France11 sites
Clermont-Ferrand University Hospital
Clermont-Ferrand
Beaujon Hospital
Clichy
Lille University Hospital
Lille
Metz-Thionville Hospital
Metz
Montpellier University Hospital
Montpellier
Nantes University Hospital
Nantes
Nimes University Hospital
Nîmes
Perigueux Hospital
Périgueux
Rennes University Hospital
Rennes
Saint-Brieuc Hospital
Saint-Brieuc
Toulouse University Hospital
Toulouse
About this study
Official title: Effect of Opioid-free Anesthesia on Postoperative Opioid-related Adverse Events After Major or Intermediate Non-cardiac Surgery: a Multicenter Prospective Randomized Controlled Study
Since the 1960's, intraoperative administration of opioids is considered a keystone of anesthesia as well as hypnotics and muscle relaxants. Synthetic opioids were introduced to achieve hemodynamic stability during anesthesia. They allow an inhibition of the sympathetic system without cardiovascular collapse and histamine release. Since then, anesthesia has changed from inhalation to multimodal anesthesia with lower doses of hypnotic. In 2017, the intraoperative objectives of hypnosis, hemodynamic stability, immobility and anticipation of postoperative analgesia can be achieved without opioids. Moreover, opioid administration consequences are neither scarce nor benign for the patient. Perioperative opioids are associated with nausea and vomiting, sedation, ileus, confusion/delirium, respiratory depression, increased postoperative pain and morphine consumption, immunodepression, hyperalgesia and chronic postoperative pain. Among these complications, hypoxemia, ileus and confusion/delirium are the most frequent.
Efficacious multimodal analgesia and anesthesia are the basis of successful fast-track surgery. These multidrug regimens aim at decreasing postoperative pain, intra- and postoperative opioid requirements, and subsequently, opioid-related adverse effects and to fasten recovery. Opioid-free postoperative analgesia has been recommended for more than 10 years. Opioid-free anesthesia (OFA) is based on the idea that hemodynamic stability can be achieved without opioids during anesthesia. OFA is multimodal anesthesia associating hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics, anti-inflammatory drugs and alpha-2 agonists (Dexmedetomidine).
Proofs of the effect of OFA on reducing opioid-related adverse effects after major or intermediate non-cardiac surgery are still scarce. We hypothesized that the reduced opioid consumption during and after surgery allowed by OFA compared with standard of care will be associated with a reduction of postoperative opioid-related adverse events.
- Conditions
- Anesthesia, Opioid-Related Disorders
- Being tested
- Dexmedetomidine, Remifentanil
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Opioid-free anesthesia
RemifentanilDrug
Opioid anesthesia
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Not described Receives: Drug: Dexmedetomidine |
| Control | Active comparator | Not described Receives: Drug: Remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of a severe postoperative opioid-related adverse event defined as : postoperative hypoxemia or postoperative ileus (POI) or postoperative cognitive dysfunction (POCD).
Postoperative hypoxemia is defined as an oxygen saturation (SpO2) < 95% with a need for oxygen supplementation within the first 48h after extubation; the duration of oxygen treatment will also be recorded.
Postoperative ileus is defined as an absence of flatus or stools within the first 48h after extubation.
Postoperative cognitive dysfunction will be evaluated using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) by a care provider (either anesthesiologist or nurse).
Measured: Within the first 48 hours after extubation
Secondary outcomes (8)
Number of episodes of postoperative pain (numeric rating scale ≥ 3), at rest
Measured: Within 48 hours after extubation
Opioid consumption
Measured: During the 48 hours following extubation
Time between the end of remifentanil or dexmedetomidine administration and an Aldrete score > 9 (when applicable)
Measured: Within 48 hours after extubation
Time between the end of remifentanil or dexmedetomidine administration and extubation
Measured: Hour 0 = extubation
Rate of unscheduled admission in intensive care unit
Measured: Within 48 hours after extubation
Number of postoperative nausea and vomiting (PONV) episodes
Measured: During the 48 hours following extubation
Hospital length of stay (max 28 days) defined as the number of days after extubation before first hospital discharge
Measured: Day 28
Number of bradycardia, hypotension and hypertension events during surgery and number of rescue medications during surgery
Bradycardia is defined as the number of episodes with atropine administration. Hypotension is defined as mean arterial blood pressure < 65 mmHg. Hypertension is defined as mean arterial blood pressure > 90 mmHg.
Measured: During surgery (maximum duration of 7 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2017
- Study start29 Nov 2017
- Primary completion29 Jan 2019
- Study completion19 Jun 2019
Why it stopped: Sponsor's decision
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 AnesthesiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 316 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hélène BELOEIL, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03316339
- Sponsor's protocol ID
- 35RC16_9842_POFA
- Acronym
- POFA
- Status last verified
- Oct 2019
- First submitted
- 13 Oct 2017
- Last updated
- 18 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Beloeil H, Laviolle B, Menard C, Paugam-Burtz C, Garot M, Asehnoune K, Minville V, Cuvillon P, Oger S, Nadaud J, Lecoeur S, Chanques G, Futier E; SFAR research network. POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. BMJ Open. 2018 Jun 30;8(6):e020873. doi: 10.1136/bmjopen-2017-020873.
PubMed 29961015
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Opioid-free Anesthesia on Postoperative Opioid-related Adverse Events After Major or Intermediate Non-cardiac Surgery: a Multicenter Prospective Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT03316339
- Acronym / sponsor ID
- POFA / 35RC16_9842_POFA
- Conditions
- Anesthesia, Opioid-Related Disorders
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 316 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 29 Nov 2017 (actual)
- Primary completion
- 29 Jan 2019 (actual)
- Study completion
- 19 Jun 2019 (actual)
- First posted
- 20 Oct 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.
Since the 1960's, intraoperative administration of opioids is considered a keystone of anesthesia as well as hypnotics and muscle relaxants. Synthetic opioids were introduced to achieve hemodynamic stability during anesthesia. They allow an inhibition of the sympathetic system without cardiovascular collapse and histamine release. Since then, anesthesia has changed from inhalation to multimodal anesthesia with lower doses of hypnotic. In 2017, the intraoperative objectives of hypnosis, hemodynamic stability, immobility and anticipation of postoperative analgesia can be achieved without opioids. Moreover, opioid administration consequences are neither scarce nor benign for the patient. Perioperative opioids are associated with nausea and vomiting, sedation, ileus, confusion/delirium, respiratory depression, increased postoperative pain and morphine consumption, immunodepression, hyperalgesia and chronic postoperative pain. Among these complications, hypoxemia, ileus and confusion/delirium are the most frequent.
Efficacious multimodal analgesia and anesthesia are the basis of successful fast-track surgery. These multidrug regimens aim at decreasing postoperative pain, intra- and postoperative opioid requirements, and subsequently, opioid-related adverse effects and to fasten recovery. Opioid-free postoperative analgesia has been recommended for more than 10 years. Opioid-free anesthesia (OFA) is based on the idea that hemodynamic stability can be achieved without opioids during anesthesia. OFA is multimodal anesthesia associating hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics, anti-inflammatory drugs and alpha-2 agonists (Dexmedetomidine).
Proofs of the effect of OFA on reducing opioid-related adverse effects after major or intermediate non-cardiac surgery are still scarce. We hypothesized that the reduced opioid consumption during and after surgery allowed by OFA compared with standard of care will be associated with a reduction of postoperative opioid-related adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: Dexmedetomidine |
| Control | Active comparator | Drug: Remifentanil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Undergoing a scheduled major or intermediate non-cardiac surgery,
- Benefiting from the health insurance system,
- Having signed an informed consent.
Key exclusion criteria (19 listed)
- Pregnant or breast feeding women,
- Allergy to dexmedetomidine or one of its excipients,
- Allergy to one of the drugs used for anesthesia or one of their excipients,
- Urgent surgery,
- Intracranial 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 |
|---|---|---|
| DexmedetomidineOpioid-free anesthesia | Drug | Dexmedetomidine |
| RemifentanilOpioid anesthesia | Drug | Control |
Primary outcome
Occurence of a severe postoperative opioid-related adverse event defined as : postoperative hypoxemia or postoperative ileus (POI) or postoperative cognitive dysfunction (POCD).
Time frame: Within the first 48 hours after extubation
Postoperative hypoxemia is defined as an oxygen saturation (SpO2) < 95% with a need for oxygen supplementation within the first 48h after extubation; the duration of oxygen treatment will also be recorded. Postoperative ileus is defined as an absence of flatus or stools within the first 48h after extubation. Postoperative cognitive dysfunction will be evaluated using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) by a care provider (either anesthesiologist or nurse).
8 secondary outcomes
Number of episodes of postoperative pain (numeric rating scale ≥ 3), at rest
Time frame: Within 48 hours after extubation
Opioid consumption
Time frame: During the 48 hours following extubation
Time between the end of remifentanil or dexmedetomidine administration and an Aldrete score > 9 (when applicable)
Time frame: Within 48 hours after extubation
Time between the end of remifentanil or dexmedetomidine administration and extubation
Time frame: Hour 0 = extubation
Rate of unscheduled admission in intensive care unit
Time frame: Within 48 hours after extubation
Number of postoperative nausea and vomiting (PONV) episodes
Time frame: During the 48 hours following extubation
Hospital length of stay (max 28 days) defined as the number of days after extubation before first hospital discharge
Time frame: Day 28
Number of bradycardia, hypotension and hypertension events during surgery and number of rescue medications during surgery
Time frame: During surgery (maximum duration of 7 hours)
Results and safety
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2019.
- Derived from this study: PubMed 29961015Beloeil H, Laviolle B, Menard C, Paugam-Burtz C, Garot M, Asehnoune K, Minville V, Cuvillon P, Oger S, Nadaud J, Lecoeur S, Chanques G, Futier E; SFAR research network. POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. BMJ Open. 2018 Jun 30;8(6):e020873. doi: 10.1136/bmjopen-2017-020873.
- Individual participant dataSharing planned: No
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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.
Hélène BELOEIL principal investigator
Rennes University Hospital
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexmedetomidine and Remifentanil in people with Anesthesia and Opioid-Related Disorders, run by Rennes University Hospital at 11 sites in France.
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 19 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: stopped early, as of the sponsor's last update on 18 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
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?
Occurence of a severe postoperative opioid-related adverse event defined as : postoperative hypoxemia or postoperative ileus (POI) or postoperative cognitive dysfunction (POCD). (time frame: Within the first 48 hours after extubation). 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 NCT03316339, 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 18 Oct 2019.