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High Dosage Buprenorphine as a Drug Strategy Withdrawal Assistance of Analgesics Opioid (SEVROP)

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ClinicalTrials.gov Identifier: NCT03156907
Recruitment Status : Recruiting
First Posted : May 17, 2017
Last Update Posted : May 1, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

Brief 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. 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 the success rate at 6 months of opioid temporary rotation by High Dosage Buprenorphine (BHD) taper dose in chronic non cancer pain patients (CNCP) with physical withdrawal symptoms making opioid withdrawal impossible.


Condition or disease Intervention/treatment Phase
High Dosage Buprenorphine Drug: Buprenorphine/naloxone Phase 2

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 start to taper off their analgesic opioid dosage according to a specific schedule. They will be seen by a doctor every month and will be contacted by phone 48-72h after every stage of opioid dosage decrease to detect withdrawal symptoms using the specific COWS scale.

The responder status is defined by the strict adherence to the schedule leading to a 50% decrease at 3 months of the initial daily dosage of the analgesic opioid. In this case, patients will continue Step 1 and will keep on tapering off their analgesic opioid according to the same protocol and will be seen by a doctor every month and will be contacted by phone 48-72h after every stage of opioid dosage decrease until total withdrawal at 6 months. At 6 months, they will undergo the same questionnaires and tests performed at baseline (BPI, HAD, LSEQ, SF 12, COWS and algometer, pupillometer). At 9 months, patients will be contacted by phone to check for the maintenance of withdrawal and to collect analgesic treatment.

The non-responder status is defined by a failure in the scheduled dosage decrease consisting in the need for the patient to re-increase the opioid dosage after a stage of decrease. These patients will enter the step 2 and start the temporary rotation by HDB (Step2).

Step 2: 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). Two visits at J0+7 days and J0+14 days are planned to assess the efficacy and safety of HDB. The treatment will be continued for a 1-month period at the same dosage. At J0+1 month, a tapering-off period of 5 months will start until total withdrawal of HDB is achieved at J0+6 months (decrease of 1 mg per month). Patients will be seen by a doctor every month and will be contacted by phone 48-72h after every stage of HDB dosage decrease until total withdrawal at J0+6 months. Questionnaires (BPI, HAD, LSEQ, SF 12, COWS) and tests (algometer and pupillometer) will be repeated at J0, J0+1 month and J0+6 months. A urinary test will be performed at J0, J0+1 month and J0+6 months to evaluate primary outcome. At 9 months, patients will be contacted by phone to check for the maintenance of withdrawal and to collect analgesic treatment.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open
Primary Purpose: Treatment
Official Title: High Dosage Buprenorphine as a Drug Strategy Withdrawal Assistance of Analgesics Opioid After Failure of an Opioid Tapering-off Strategy.
Actual Study Start Date : September 15, 2017
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Chronic pain patients
The primary objective of this study is to assess the success rate at 6 months of opioid temporary rotation by High Dosage Buprenorphine (BHD) taper dose in chronic non cancer pain patients (CNCP) with physical withdrawal symptoms making opioid withdrawal impossible.
Drug: Buprenorphine/naloxone
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).




Primary Outcome Measures :
  1. Absence of opioid in urine test after rotation by HDB [ Time Frame: Month 6 ]
    Validating total opioid withdrawal (including HDB)


Secondary Outcome Measures :
  1. Rate of opioid tapering-off protocol success by decrease of 50% of initial posology [ Time Frame: Month 3 ]
  2. Rate of opioid tapering-off protocol success by total taper opioid withdrawal [ Time Frame: Month 6 ]
  3. The pain will be assessed by the questionnaire Brief pain Inventory (BPI) [ Time Frame: Day 1, Month 1, Month 6 ]
  4. 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 ]
  5. The anxiety and depression will be assessed by questionnaire HAD (Hospital anxiety and depression scale) [ Time Frame: Day 1, Month 1, Month 6 ]
  6. The sleep will be assessed by questionnaire LSEQ (Leeds sleep evaluation questionnaire) [ Time Frame: Day 1, Month 1, Month 6 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • be ≥ 18 years,
  • have CNCP treated since more 6 months by only one analgesic opioid (weak or strong/ LP or LI), for chronic non cancer pain,
  • have an indication to stop or decrease analgesic opioid treatment (no indicate, tolerance, inefficacity or sides effects) and/or have opioid physical withdrawal symptom between two administration (assess to Clinical Opiate Withdrawal Scale (COWS)),
  • have given informed consent and be affiliated to the French Social Security.

Exclusion Criteria:

  • be ≤ 18 years,
  • have at last 2 different analgesics opioid in the same time (weak or strong),
  • have a treatment with ketamine,
  • have a chronic cancer pain,
  • have a opioid analgesic treatment since less 6 months,
  • not have an indication to stop or decrease analgesic opioid treatment,
  • not have physical withdrawal symptom during decrease or stop opioid analgesic treatment,
  • have a opioid misuse or addiction (assess by Prescription Opioid Misuse Index (POMI)),
  • have licit or illicit opioids dependence, be treated or not by opioid substitution treatment,
  • have a contraindication to high dosage buprenorphine (hypersensitivity to active substance or the excipients, severe hepatic dysfunction, severe respiratory dysfunction, alcohol addiction or delirium tremens),
  • have alcohol dependence,
  • have buprenorphine or methadone treatment,
  • women pregnant or breastfeeding,
  • be involved in any other interventional trial, and inability to understand patients' information and informed consent form and patients undergoing a measure of legal protection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03156907


Contacts
Contact: Patrick LACARIN 04 73 75 11 95 placarin@chu-clermontferrand.fr
Contact: Noémie DELAGE 04 73 17 84 30 ndelage@chu-clermontferrand.fr

Locations
France
CHU Clermont-Ferrand Recruiting
Clermont-Ferrand, Auvergne, France, 63003
Contact: Patrick LACARIN    04 73 75 11 95    placarin@chu-clermontferrand.fr   
Contact: Noémie DELAGE    04 73 17 84 30    ndelage@chu-clermontferrand.fr   
Sponsors and Collaborators
University Hospital, Clermont-Ferrand

Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT03156907     History of Changes
Other Study ID Numbers: CHU-325
2015-003173-15 ( Other Identifier: 2015-003173-15 )
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Clermont-Ferrand:
High dosage Buprenorphine (HDB)
Chronic pain
Analgesics opioids
Withdrawal symptoms

Additional relevant MeSH terms:
Analgesics, Opioid
Buprenorphine
Buprenorphine, Naloxone Drug Combination
Analgesics
Naloxone
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists