High Dosage BuprenorphinePhase 2SEVROPNCT03156907
High Dosage Buprenorphine as a Drug Strategy Withdrawal Assistance of Analgesics Opioid
A Phase 2 study testing Buprenorphine in people with High Dosage Buprenorphine, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
The prevalence of analgesics opioids addiction in chronic pain patient is very difficult to know. Many studies indicated that the prevalence of addiction varied from 0% up to 50% in chronic non cancer pain patients, and from 0% up to 7.7% in cancer pain patients. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- High Dosage Buprenorphine
- What is being tested?
- Buprenorphine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 15 Sep 2017to Mar 2025
- Phase
- Phase 2
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients >= 18 years,
- patients with CNCP who have been treated for more than 6 months with a single opioid analgesic (weak or strong; long acting and/or immediate release),
- Patients will be required to have an indication to stop or reduce opioid therapy (i.e. unfounded indication, tolerance, ineffectiveness, and/or adverse effects), and/or have physical withdrawal symptoms between opioid administrations (Clinical Opioid Withdrawal Scale (COWS) assessment),
- Patients must have given their comprehensive informed consent and be affiliated with the French social security system.
Who cannot join
- not have an opioid use disorder with craving (assessment by investigator according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)) or misuse (assessment by the Prescription Opioid Misuse Index (POMI)[28]) related to opioid use,
- ongoing treatment with ketamine,
- chronic cancer pain,
- contraindication to buprenorphine (hypersensitivity to an active substance or its excipients, severe hepatic and/or respiratory dysfunction, alcohol use disorder or delirium tremens),
- alcohol use disorder,
- pregnant or breastfeeding,
- involved in any other interventional trial, or be subject to legal protection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: High Dosage Buprenorphine as a Drug Strategy Withdrawal Assistance of Analgesics Opioid After Failure of an Opioid Tapering-off Strategy.
The prevalence of analgesics opioids addiction in chronic pain patient is very difficult to know. Many studies indicated that the prevalence of addiction varied from 0% up to 50% in chronic non cancer pain patients, and from 0% up to 7.7% in cancer pain patients. Analgesics opioids use have increasingly been increased in chronic pain for 20 years. However, a long use, at least 3 months in this type of pain has not proved a large efficiency and we have noticed a habituation, tolerance and withdrawal when treatment was decreased or stopped. In current practice, patients with chronic pain, often keep their analgesics opioids despite the absence of pain relief and benefits in quality of life.
Nowadays, no withdrawal strategy is the reference in chronic non-cancer pain patients with physical opioid dependence. The most common clinical strategy is progressive decrease of analgesic opioid. But this strategy is often a failure in these patients (no data are available in literature).
Read more
It's necessary to make a prospective pilot study to assess benefits from this practice.
The primary objective of this study is to assess a new ambulatory withdrawal strategy, consisting of a temporary opioid rotation with buprenorphine in CNCP patients suffering from physical withdrawal symptoms and who have failed a conventional strategy of progressive withdrawal from their opioid analgesic treatment.
Read the detailed description
This study is designed as a type 2 multicenter clinical trial combining 3 Pain Clinics.
Patients were consecutively recruited from the active file of 3 Pain Clinics in France (Clermont-Ferrand, Vichy and le Puy-en-Velay). Patients meeting all inclusion criteria were enrolled after receiving oral and written information about the study and after obtaining written informed consent.
At baseline, they completed 5 questionnaires including: Brief Pain Inventory (BPI), Hospital Anxiety and Depression scale (HAD), Leeds sleep Evaluation Questionnaire (LSEQ), Short version of Short Form 36 Health Survey (SF 12), Clinical Opioid Withdrawal Scale (COWS) and underwent 2 tests with algometer and pupillometer. After inclusion, all patients started an opioid tapering-off protocol (Figure 1, Step 1) according to a standardized scheme of opioid gradual decrease defined by 3 medical experts in addictology, pain management and pharmacology.
Step 1 (from inclusion to 3 months): Patients will start to taper off their opioid dose according to a specific schedule. They will be seen by a physician on a monthly basis and contacted by phone 48-72h after each decrease in opioid dosage to detect withdrawal symptoms using the COWS specific scale. After 3 months, all patients who fail the opioid tapering-off protocol will be included in a non-responder group, while the others who succeed the withdrawal protocol will be included in a responder group:
- A responder will be defined by strict adherence to the schedule leading to a 50% reduction in the initial daily dose of opioid after 3 months. In this case, patients will continue with step 1 and decrease their opioid dose according to the same withdrawal protocol. They will be seen by a physician on a monthly basis and contacted by phone 48-72h after each stage of opioid dose reduction, until the opioid treatment is completely discontinued after 6 months of the withdrawal protocol. At 6 months, patients will fill out the same questionnaires and perform the same tests as at the baseline visit. Finally, after 9 months, patients will be contacted by phone to check that withdrawal is being maintained and to collect data on ongoing analgesic treatment.
- A non-responder will be defined as a failure of the withdrawal protocol, by non-compliance with the schedule, leading to a 50% reduction in the initial daily dose of opioid treatment after 3 months or when tapering off fails, leading the patient to re-increase the opioid dose. Thus, these patients will proceed to step 2 and start temporary rotation with buprenorphine.
Step 2:
- From D0 to D0+28 days - buprenorphine treatment/stabilization Buprenorphine will be administered initially (D0) for 28 days at a dose of 4 mg/day (possible adjustment of ±2mg/day with the possibility to increase the dose up to 8 mg/day during the first 24-48 hours, depending on the severity of withdrawal symptoms or patient tolerance). Questionnaires (BPI, HADS, LSEQ, SF-12, COWS) and tests (algometer and pupillometer) will be completed at D0, and the physician will assess the efficacy and safety of buprenorphine by phone call at D0 + 24h/48 h and at D0 + 7 days.
- From D0 + 28 days to D0 + 9th month after rotation by buprenorphine The buprenorphine treatment will be tapered off in 1 mg steps every 28 days until the complete cessation of buprenorphine after 9 months of withdrawal. Patients will be seen by a physician every 28 days and will be contacted by phone 48-72h after each decrease in the buprenorphine dose. The COWS questionnaires and a pain assessment (11-point NRS) will be completed at each medical consultation.
- D0 + 9th month A urine opioid test (primary outcome) will be performed to validate the total opioid withdrawal (including buprenorphine). Patients will complete different questionnaires (BPI, HADS, LSEQ, SF 12, COWS) and perform different tests (algometer and pupillometer).
- Follow-up phone call at 12 months The patients will be contacted by phone to check on their continued withdrawal and ongoing analgesic treatment.
- Conditions
- High Dosage Buprenorphine
- Being tested
- Buprenorphine
- Keywords
- High dosage Buprenorphine (HDB), Chronic pain, Analgesics opioids, Withdrawal symptoms
- Medical subject headings
- Chronic Pain, Substance Withdrawal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
HDB is started (J0) at the dosage of 4 mg/ day (with a possible adjustment ± 2 mg at 24h, depending on the patient withdrawal symptoms intensity or tolerance).
| Study group | Role | What they receive |
|---|---|---|
| Chronic pain patients | Experimental | The primary objective of this study is to assess the success rate at 6 months of opioid temporary rotation by High Dosage Buprenorphine (HDB) taper dose in chronic non cancer pain patients (CNCP) with physical withdrawal symptoms making opioid withdrawal impossible. Receives: Drug: Buprenorphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absence of opioid in urine test after rotation by HDB
Validating total opioid withdrawal (including HDB)
Measured: Month 6
Secondary outcomes (8)
Rate of opioid tapering-off protocol success by decrease of 50% of initial posology
Measured: Month 3
Rate of opioid tapering-off protocol success by total taper opioid withdrawal
Measured: Month 6
The pain will be assessed by the questionnaire Brief pain Inventory (BPI)
Measured: Day 1, Month 1, Month 6
The quality of life will be assessed by questionnaire SF12 (Short version of Short Form 36 Health Survey)
Measured: Day 1, Month 1, Month 6
The anxiety and depression will be assessed by questionnaire HAD (Hospital anxiety and depression scale)
Measured: Day 1, Month 1, Month 6
The sleep will be assessed by questionnaire LSEQ (Leeds sleep evaluation questionnaire)
Measured: Day 1, Month 1, Month 6
Evaluation of the correlation between pupillary dilation (pupillometer) and pain (NRS 0-10).
Measured: Day 1, Month 1, Month 6
Evaluation of pain intensity (NRS 0-10) by the pressure algometry measurement.
Measured: Day 1, Month 1, Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2017
- Study start15 Sep 2017
- Primary completionDec 2024 (estimated)
- Study completionMar 2025 (estimated)
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 High Dosage BuprenorphineStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03156907
- Sponsor's protocol ID
- CHU-325
- Other IDs
- 2015-003173-15, 2015
- Acronym
- SEVROP
- Status last verified
- Jun 2021
- First submitted
- 5 May 2017
- Last updated
- 6 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bertin C, Kerckhove N, Ferrer F, Pereira B, Duale C, Richard D, Authier N, Delage N. Buprenorphine Substitution as a Tapering Strategy for Opioid Discontinuation in Patients with Chronic Pain: A Nonrandomized and Proof of Concept Study. Pain Ther. 2025 Dec;14(6):1783-1795. doi: 10.1007/s40122-025-00781-z. Epub 2025 Oct 3.
PubMed 41042438
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dosage Buprenorphine as a Drug Strategy Withdrawal Assistance of Analgesics Opioid After Failure of an Opioid Tapering-off Strategy.
- ClinicalTrials.gov ID
- NCT03156907
- Acronym / sponsor ID
- SEVROP / CHU-325
- Conditions
- High Dosage Buprenorphine
- Keywords
- High dosage Buprenorphine (HDB), Chronic pain, Analgesics opioids, Withdrawal symptoms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 17 May 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.
The prevalence of analgesics opioids addiction in chronic pain patient is very difficult to know. Many studies indicated that the prevalence of addiction varied from 0% up to 50% in chronic non cancer pain patients, and from 0% up to 7.7% in cancer pain patients. Analgesics opioids use have increasingly been increased in chronic pain for 20 years. However, a long use, at least 3 months in this type of pain has not proved a large efficiency and we have noticed a habituation, tolerance and withdrawal when treatment was decreased or stopped. In current practice, patients with chronic pain, often keep their analgesics opioids despite the absence of pain relief and benefits in quality of life.
Nowadays, no withdrawal strategy is the reference in chronic non-cancer pain patients with physical opioid dependence. The most common clinical strategy is progressive decrease of analgesic opioid. But this strategy is often a failure in these patients (no data are available in literature).
It's necessary to make a prospective pilot study to assess benefits from this practice.
The primary objective of this study is to assess a new ambulatory withdrawal strategy, consisting of a temporary opioid rotation with buprenorphine in CNCP patients suffering from physical withdrawal symptoms and who have failed a conventional strategy of progressive withdrawal from their opioid analgesic treatment.
Detailed description
This study is designed as a type 2 multicenter clinical trial combining 3 Pain Clinics.
Patients were consecutively recruited from the active file of 3 Pain Clinics in France (Clermont-Ferrand, Vichy and le Puy-en-Velay). Patients meeting all inclusion criteria were enrolled after receiving oral and written information about the study and after obtaining written informed consent.
At baseline, they completed 5 questionnaires including: Brief Pain Inventory (BPI), Hospital Anxiety and Depression scale (HAD), Leeds sleep Evaluation Questionnaire (LSEQ), Short version of Short Form 36 Health Survey (SF 12), Clinical Opioid Withdrawal Scale (COWS) and underwent 2 tests with algometer and pupillometer. After inclusion, all patients started an opioid tapering-off protocol (Figure 1, Step 1) according to a standardized scheme of opioid gradual decrease defined by 3 medical experts in addictology, pain management and pharmacology.
Step 1 (from inclusion to 3 months): Patients will start to taper off their opioid dose according to a specific schedule. They will be seen by a physician on a monthly basis and contacted by phone 48-72h after each decrease in opioid dosage to detect withdrawal symptoms using the COWS specific scale. After 3 months, all patients who fail the opioid tapering-off protocol will be included in a non-responder group, while the others who succeed the withdrawal protocol will be included in a responder group:
- A responder will be defined by strict adherence to the schedule leading to a 50% reduction in the initial daily dose of opioid after 3 months. In this case, patients will continue with step 1 and decrease their opioid dose according to the same withdrawal protocol. They will be seen by a physician on a monthly basis and contacted by phone 48-72h after each stage of opioid dose reduction, until the opioid treatment is completely discontinued after 6 months of the withdrawal protocol. At 6 months, patients will fill out the same questionnaires and perform the same tests as at the baseline visit. Finally, after 9 months, patients will be contacted by phone to check that withdrawal is being maintained and to collect data on ongoing analgesic treatment.
- A non-responder will be defined as a failure of the withdrawal protocol, by non-compliance with the schedule, leading to a 50% reduction in the initial daily dose of opioid treatment after 3 months or when tapering off fails, leading the patient to re-increase the opioid dose. Thus, these patients will proceed to step 2 and start temporary rotation with buprenorphine.
Step 2:
- From D0 to D0+28 days - buprenorphine treatment/stabilization Buprenorphine will be administered initially (D0) for 28 days at a dose of 4 mg/day (possible adjustment of ±2mg/day with the possibility to increase the dose up to 8 mg/day during the first 24-48 hours, depending on the severity of withdrawal symptoms or patient tolerance). Questionnaires (BPI, HADS, LSEQ, SF-12, COWS) and tests (algometer and pupillometer) will be completed at D0, and the physician will assess the efficacy and safety of buprenorphine by phone call at D0 + 24h/48 h and at D0 + 7 days.
- From D0 + 28 days to D0 + 9th month after rotation by buprenorphine The buprenorphine treatment will be tapered off in 1 mg steps every 28 days until the complete cessation of buprenorphine after 9 months of withdrawal. Patients will be seen by a physician every 28 days and will be contacted by phone 48-72h after each decrease in the buprenorphine dose. The COWS questionnaires and a pain assessment (11-point NRS) will be completed at each medical consultation.
- D0 + 9th month A urine opioid test (primary outcome) will be performed to validate the total opioid withdrawal (including buprenorphine). Patients will complete different questionnaires (BPI, HADS, LSEQ, SF 12, COWS) and perform different tests (algometer and pupillometer).
- Follow-up phone call at 12 months The patients will be contacted by phone to check on their continued withdrawal and ongoing analgesic treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chronic pain patients | Experimental | Drug: BuprenorphineThe primary objective of this study is to assess the success rate at 6 months of opioid temporary rotation by High Dosage Buprenorphine (HDB) taper dose in chronic non cancer pain patients (CNCP) with physical withdrawal symptoms making opioid withdrawal impossible. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients >= 18 years,
- patients with CNCP who have been treated for more than 6 months with a single opioid analgesic (weak or strong; long acting and/or immediate release),
- Patients will be required to have an indication to stop or reduce opioid therapy (i.e. unfounded indication, tolerance, ineffectiveness, and/or adverse effects), and/or have physical withdrawal symptoms between opioid administrations (Clinical Opioid Withdrawal Scale (COWS) assessment),
- Patients must have given their comprehensive informed consent and be affiliated with the French social security system.
Key exclusion criteria (7 listed)
- not have an opioid use disorder with craving (assessment by investigator according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)) or misuse (assessment by the Prescription Opioid Misuse Index (POMI)[28]) related to opioid use,
- ongoing treatment with ketamine,
- chronic cancer pain,
- contraindication to buprenorphine (hypersensitivity to an active substance or its excipients, severe hepatic and/or respiratory dysfunction, alcohol use disorder or delirium tremens),
- alcohol use disorder,
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 |
|---|---|---|
| BuprenorphineHDB is started (J0) at the dosage of 4 mg/ day (with a possible adjustment ± 2 mg at 24h, depending on the patient withdrawal symptoms intensity or tolerance). | Drug | Chronic pain patients |
Primary outcome
Absence of opioid in urine test after rotation by HDB
Time frame: Month 6
Validating total opioid withdrawal (including HDB)
8 secondary outcomes
Rate of opioid tapering-off protocol success by decrease of 50% of initial posology
Time frame: Month 3
Rate of opioid tapering-off protocol success by total taper opioid withdrawal
Time frame: Month 6
The pain will be assessed by the questionnaire Brief pain Inventory (BPI)
Time frame: Day 1, Month 1, Month 6
The quality of life will be assessed by questionnaire SF12 (Short version of Short Form 36 Health Survey)
Time frame: Day 1, Month 1, Month 6
The anxiety and depression will be assessed by questionnaire HAD (Hospital anxiety and depression scale)
Time frame: Day 1, Month 1, Month 6
The sleep will be assessed by questionnaire LSEQ (Leeds sleep evaluation questionnaire)
Time frame: Day 1, Month 1, Month 6
Evaluation of the correlation between pupillary dilation (pupillometer) and pain (NRS 0-10).
Time frame: Day 1, Month 1, Month 6
Evaluation of pain intensity (NRS 0-10) by the pressure algometry measurement.
Time frame: Day 1, Month 1, Month 6
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
- Derived from this study: PubMed 41042438Bertin C, Kerckhove N, Ferrer F, Pereira B, Duale C, Richard D, Authier N, Delage N. Buprenorphine Substitution as a Tapering Strategy for Opioid Discontinuation in Patients with Chronic Pain: A Nonrandomized and Proof of Concept Study. Pain Ther. 2025 Dec;14(6):1783-1795. doi: 10.1007/s40122-025-00781-z. Epub 2025 Oct 3.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buprenorphine in people with High Dosage Buprenorphine, run by University Hospital, Clermont-Ferrand at 1 site 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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 6 Jul 2021. 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 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Absence of opioid in urine test after rotation by HDB (time frame: Month 6). 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 NCT03156907, 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 6 Jul 2021.