Chronic PainPhase 4NCT02032927
Treatment of Chronic Pain From Osteoarthritis
A Phase 4 study testing Codeine/paracetamol and Oxycodone/naloxone in people with Chronic Pain, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 14 sites in Italy.
Trial summary
Osteoarthritis is a common joint disorder in the elder population.The current treatment options include both a non-pharmacological approach (physiokinesitherapy, diet) or if this fails, a pharmacological approach that relies in the first instance on drugs such as paracetamol, non-steroidal anti-inflammatory (including… Read more about this study
- Who is it for?
- Ages 60 to 100 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- Codeine/paracetamol and Oxycodone/naloxone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 14 sitesItaly
- Study dates
- Jun 2013to Jun 2015
- Phase
- Phase 4
- 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 60 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects over the age of 60 years old
- Individuals with a primary diagnosis of osteoarthritis
- Subject that are able to understand the purpose of the study and that have signed a written informed consent
- Subjects that are able to take prescribed therapies, understand and complete the questionnaires and forms
Who cannot join
- Subject with history of hypersensitivity to oxycodone, naloxone , codeine , acetaminophen, ibuprofen, and the other ingredients in the formulations studied
- Subjects with known structural alterations in the gastrointestinal tract
- Subjects with secondary osteoarthritis
- Subjects with history of abuse of alcohol and / or drugs
- Subjects with history of abuse opioids.
- Patients suffering from rheumatoid arthritis
Show all 12Show fewer
- Patients with evidence of medical or surgical unstable
- Patients with current or previous history of epilepsy
- Patients treated with anti-depressive action on the central nervous system which in the opinion of the investigator may result in additive effects with the drugs under study.
- Subjects with renal and / or hepatic impairment severe
- Subjects with a history of depression or other psychiatric condition that, in the opinion of the investigator might interfere with the study participation
- Individuals with cognitive impairment
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Italy14 sites
Azienda Ospedaliera della Provincia di Pavia - Ospedale "Carlo Mira" - U.O. Medicina Interna - Servizio di Anestesia e Rianimazione - Ambulatorio di Terapia del dolore
Casorate Primo
Azienda Istituti Ospitalieri di Cremona, Presidio Ospedaliero di Cremona - U.O. di Anestesia, Analgesia e Medicina Perioperatoria
Cremona
Azienda Ospedaliera della provincia di Lodi Dipartimento emergenza urgenza
Lodi
Azienda Ospedaliera Istituto Ortopedico Gaetano Pini - U.O.C. Anestesia e Rianimazione
Milan
Azienda Ospedaliera della Provincia di Pavia - Ospedale Asilo Vittoria di Mortara - U.O. di Pneumotisiologia
Mortara
Clinica San Carlo - Casa di Cura Polispecialistica S.p.A. - Unità di Terapia del Dolore
Paderno Dugnano
Fondazione IRCCS Policlinico San Matteo
Pavia, Pavia, 27100
Azienda Servizi alla Persona, ASP, "II.AA.RR." - Istituto di Riabilitazione "Santa Margherita" - Struttura Complessa di Riabilitazione
Pavia
Fondazione Salvatore Maugeri - sede di Via Boezio - UO Cure Palliative e Terapia del Dolore
Pavia
IRCCS Istituto Clinico "Humanitas" - Anestesia, Day Hospital chirurgico - Chronic Pain Service
Rozzano
Dipartimento Integrato di Lungassistenza Anziani - ASL TO1
Torino
Ospedale di circolo Fondazione Macchi - SSD Anestesia Day Surgery
Varese
Azienda Ospedaliera della Provincia di Pavia - Ospedale Civile di Vigevano - Servizio di Anestesia e Rianimazione
Vigevano
Azienda Ospedaliera della Provincia di Pavia - Ospedale Civile di Voghera- U.O. di Medicina Interna - U.O. di Riabilitazione specialistica
Voghera
About this study
Official title: A COMPARATIVE STUDY BETWEEN TWO PHARMACOLOGICAL ASSOCIATIONS OXYCODONE/NALOXONE AND CODEINE / PARACETAMOL IN TREATMENT OF MODERATE-SEVERE CHRONIC PAIN DUE TO OSTEOARTHRITIS OF KNEE AND/OR HIP
Osteoarthritis is a common joint disorder in the elder population.The current treatment options include both a non-pharmacological approach (physiokinesitherapy, diet) or if this fails, a pharmacological approach that relies in the first instance on drugs such as paracetamol, non-steroidal anti-inflammatory (including inhibitors of cyclo-oxygenase). However, the use of these drugs is limited, by the roof effect concerning analgesia, and by the potential side effects. When pharmacological treatments with non-opioid medications fail, and a moderate-to-severe pain reduces the quality of life of the patient, international guidelines suggest the use of opioid drugs.
Read the detailed description
The WHO analgesic ladder, even with its limitations, is widely used to guide the beginning of opioid therapy in chronic pain. According to this approach the choice of drug is based on the intensity of pain reported by the patient; belong to the first step acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), and if these drugs fail it is planned to introduce a weak opioid (tramadol, codeine) alone or in combination.
The association codeine-paracetamol, one of the most widely used drug combinations in the treatment of moderate pain from osteoarthritis, demonstrated analgesic efficacy superior only to paracetamol in the short term; however, its use was less effective in the long term and worsen by multiple side effects, especially gastrointestinal with results in poor adherence to the therapy.
Lately, the international guidelines on the treatment of chronic pain in cancer have suggested the possibility of moving, in case of inadequate efficacy of paracetamol and / or NSAIDs, directly to the third step, using a low dose of a strong opioid.
The side effects associated with the use of opioids in the treatment of chronic pain, such as itching, side effects of gastrointestinal and central nervous system effects (drowsiness, giddiness), often necessitate dose reduction (thus compromising the analgesic effect), with often resulting in discontinuation of treatment.
A recent strategy to face the underlying cause of opioid-induced constipation (OIC) is the oral administration of an antagonist of opioid receptor that acts specifically and locally at the level of the gastrointestinal tract. This prevents or minimizes gastrointestinal side effects but does not affect the central analgesic effect of the opioid thank to the low bioavailability of the antagonist.
A recent review on the effects of chronic pain on cognitive function of patients describes a series of clinical evidence suggestive of a intellectual impairment predominantly associated with a significant psychomotor slowing.
An interesting corollary of the problematic pain-cognition is represented by the possible neuropsychological side effect due to teh use of opioid drugs in the treatment of chronic pain.
The objective of the research becomes to determinate how much the analgesic relief, derived from the assumption of opioid drugs, can lead to an improvement in cognitive function without the possible side effects of the drugs themselves.
- Conditions
- Chronic Pain
- Being tested
- Codeine/paracetamol, Oxycodone/naloxone
- Keywords
- osteoarthritis, pain, opioids
- Medical subject headings
- Chronic Pain, Osteoarthritis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Codeine/paracetamolDrug
Randomization to one of the two treatments will be done through appropriate randomization list.
During the first 15 days of treatment in the event of failure of efficacy, understood as the average pain intensity higher than 4 (monitored with NRS) with the need to take more than two rescue doses of paracetamol per day, and in the absence of side effects, the patients will be instructed on how to proceed with dosage adjustments according to specific guidelines.
The patient will be evaluated at 15 days, 1 month, 2 months and three months. Your health care professional who administer the assessment scales (WOMAC, SF-12, BFI, TMT) will not know in any way which treatment the patient is taking.
Oxycodone/naloxoneDrug
Randomization to one of the two treatments will be done through appropriate randomization list.
During the first 15 days of treatment in the event of failure of efficacy, understood as the average pain intensity higher than 4 (monitored with NRS) with the need to take more than two rescue doses of paracetamol per day, and in the absence of side effects, the patients will be instructed on how to proceed with dosage adjustments according to specific guidelines.
The patient will be evaluated at 15 days, 1 month, 2 months and three months. Your health care professional who administer the assessment scales (WOMAC, SF-12, BFI, TMT) will not know in any way which treatment the patient is taking.
| Study group | Role | What they receive |
|---|---|---|
| Codeine/paracetamol | Active comparator | The combination codeine/paracetamol,30 mg/500 mg,1 tablet every 8 hours, paracetamol 500 mg if NRS> 4, repeatable up to 3 times per day.
At any stage of the study, patients treated with combination codeine/paracetamol in case of ineffectiveness (NRS> 4) despite maximal dosage (2 tablets every 8 hours) and/or side effect, will be subject to the opioid switch and will start equianalgesic therapy with oxycodone/naloxone combination. Receives: Drug: Codeine/paracetamol |
| Oxycodone/Naloxone | Active comparator | Combination oxycodone /naloxone, 5 mg/2.5 mg, 1 tablet/day, paracetamol 500 mg if NRS> 4, repeatable up to 3 times per day. Receives: Drug: Oxycodone/naloxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate differences in terms of efficacy and tolerability between two pharmaceutical protocols in patients with chronic pain due to osteoarthritis.
The number of patients has been estimated considering that, at 15 days of enrollment, a reduction of 30% of the WOMAC pain subscale, with a score at BFI <50, the use of not more than one laxative drug or the absence of side effects such as to consider the need to discontinue therapy occurs in 80% of patients in Protocol B versus 50% of patients in Protocol A, with 73 patients per group will be able to highlight an odds ratio (OR) 2.65 with a power of 80% and an alpha error of 5% (2-tailed). The calculation was performed with nQuery 4 (Statistical Solutions, Cork, IRL).
Considering a drop out rate of about 24% is numerosity you plan to enroll a total of 182 patients in order to obtain 146 patients valid.
Measured: 15 days from the enrolment
Secondary outcomes (3)
Evaluate the differences between the two drug protocols, in terms of quality of life, by using of the SF-12 questionnaire.
Measured: 3 months from the enrollment
Evaluation of the differences between the two drug protocols, in the scores obtained in the two sections, functionality and rigidity of the WOMAC questionnaire.
Measured: 3 months from the enrollment
The evaluation of the attentive functions (selective and divided attention) and of eye-manual coordination and of psycho-motor speed will be performed trough Trail Making Test (Reitan, 1944) to all patients enrolled for the project.
The secondary endpoints, all on a continuous scale, will be analyzed using the Mann-Whitney U test; for each group will be reported median and quartiles.
Measured: 3 months from the enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2014 (estimated)
- Study startJun 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Massimo Allegri, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Massimo Allegri, MD, Principal investigator, IRCCS Fondazione San Matteo Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02032927
- Sponsor's protocol ID
- PT-SM-14-OA
- Status last verified
- Apr 2017
- First submitted
- 8 Jan 2014
- Last updated
- 19 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A COMPARATIVE STUDY BETWEEN TWO PHARMACOLOGICAL ASSOCIATIONS OXYCODONE/NALOXONE AND CODEINE / PARACETAMOL IN TREATMENT OF MODERATE-SEVERE CHRONIC PAIN DUE TO OSTEOARTHRITIS OF KNEE AND/OR HIP
- ClinicalTrials.gov ID
- NCT02032927
- Acronym / sponsor ID
- PT-SM-14-OA
- Conditions
- Chronic Pain
- Keywords
- osteoarthritis, pain, opioids
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Jun 2013 (actual)
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 10 Jan 2014 (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.
Osteoarthritis is a common joint disorder in the elder population.The current treatment options include both a non-pharmacological approach (physiokinesitherapy, diet) or if this fails, a pharmacological approach that relies in the first instance on drugs such as paracetamol, non-steroidal anti-inflammatory (including inhibitors of cyclo-oxygenase). However, the use of these drugs is limited, by the roof effect concerning analgesia, and by the potential side effects. When pharmacological treatments with non-opioid medications fail, and a moderate-to-severe pain reduces the quality of life of the patient, international guidelines suggest the use of opioid drugs.
Detailed description
The WHO analgesic ladder, even with its limitations, is widely used to guide the beginning of opioid therapy in chronic pain. According to this approach the choice of drug is based on the intensity of pain reported by the patient; belong to the first step acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), and if these drugs fail it is planned to introduce a weak opioid (tramadol, codeine) alone or in combination.
The association codeine-paracetamol, one of the most widely used drug combinations in the treatment of moderate pain from osteoarthritis, demonstrated analgesic efficacy superior only to paracetamol in the short term; however, its use was less effective in the long term and worsen by multiple side effects, especially gastrointestinal with results in poor adherence to the therapy.
Lately, the international guidelines on the treatment of chronic pain in cancer have suggested the possibility of moving, in case of inadequate efficacy of paracetamol and / or NSAIDs, directly to the third step, using a low dose of a strong opioid.
The side effects associated with the use of opioids in the treatment of chronic pain, such as itching, side effects of gastrointestinal and central nervous system effects (drowsiness, giddiness), often necessitate dose reduction (thus compromising the analgesic effect), with often resulting in discontinuation of treatment.
A recent strategy to face the underlying cause of opioid-induced constipation (OIC) is the oral administration of an antagonist of opioid receptor that acts specifically and locally at the level of the gastrointestinal tract. This prevents or minimizes gastrointestinal side effects but does not affect the central analgesic effect of the opioid thank to the low bioavailability of the antagonist.
A recent review on the effects of chronic pain on cognitive function of patients describes a series of clinical evidence suggestive of a intellectual impairment predominantly associated with a significant psychomotor slowing.
An interesting corollary of the problematic pain-cognition is represented by the possible neuropsychological side effect due to teh use of opioid drugs in the treatment of chronic pain.
The objective of the research becomes to determinate how much the analgesic relief, derived from the assumption of opioid drugs, can lead to an improvement in cognitive function without the possible side effects of the drugs themselves.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Codeine/paracetamol | Active comparator | Drug: Codeine/paracetamolThe combination codeine/paracetamol,30 mg/500 mg,1 tablet every 8 hours, paracetamol 500 mg if NRS> 4, repeatable up to 3 times per day. At any stage of the study, patients treated with combination codeine/paracetamol in case of ineffectiveness (NRS> 4) despite maximal dosage (2 tablets every 8 hours) and/or side effect, will be subject to the opioid switch and will start equianalgesic therapy with oxycodone/naloxone combination. |
| Oxycodone/Naloxone | Active comparator | Drug: Oxycodone/naloxoneCombination oxycodone /naloxone, 5 mg/2.5 mg, 1 tablet/day, paracetamol 500 mg if NRS> 4, repeatable up to 3 times per day. |
Who may qualify
- Ages
- 60 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects over the age of 60 years old
- Individuals with a primary diagnosis of osteoarthritis
- Subject that are able to understand the purpose of the study and that have signed a written informed consent
- Subjects that are able to take prescribed therapies, understand and complete the questionnaires and forms
Key exclusion criteria (12 listed)
- Subject with history of hypersensitivity to oxycodone, naloxone , codeine , acetaminophen, ibuprofen, and the other ingredients in the formulations studied
- Subjects with known structural alterations in the gastrointestinal tract
- Subjects with secondary osteoarthritis
- Subjects with history of abuse of alcohol and / or drugs
- Subjects with history of abuse opioids.
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 |
|---|---|---|
| Codeine/paracetamolRandomization to one of the two treatments will be done through appropriate randomization list. During the first 15 days of treatment in the event of failure of efficacy, understood as the average pain intensity higher than 4 (monitored with NRS) with the need to take more than two rescue doses of paracetamol per day, and in the absence of side effects, the patients will be instructed on how to proceed with dosage adjustments according to specific guidelines. The patient will be evaluated at 15 days, 1 month, 2 months and three months. Your health care professional who administer the assessment scales (WOMAC, SF-12, BFI, TMT) will not know in any way which treatment the patient is taking. | Drug | Codeine/paracetamol |
| Oxycodone/naloxoneRandomization to one of the two treatments will be done through appropriate randomization list. During the first 15 days of treatment in the event of failure of efficacy, understood as the average pain intensity higher than 4 (monitored with NRS) with the need to take more than two rescue doses of paracetamol per day, and in the absence of side effects, the patients will be instructed on how to proceed with dosage adjustments according to specific guidelines. The patient will be evaluated at 15 days, 1 month, 2 months and three months. Your health care professional who administer the assessment scales (WOMAC, SF-12, BFI, TMT) will not know in any way which treatment the patient is taking. | Drug | Oxycodone/Naloxone |
Primary outcome
Evaluate differences in terms of efficacy and tolerability between two pharmaceutical protocols in patients with chronic pain due to osteoarthritis.
Time frame: 15 days from the enrolment
The number of patients has been estimated considering that, at 15 days of enrollment, a reduction of 30% of the WOMAC pain subscale, with a score at BFI <50, the use of not more than one laxative drug or the absence of side effects such as to consider the need to discontinue therapy occurs in 80% of patients in Protocol B versus 50% of patients in Protocol A, with 73 patients per group will be able to highlight an odds ratio (OR) 2.65 with a power of 80% and an alpha error of 5% (2-tailed). The calculation was performed with nQuery 4 (Statistical Solutions, Cork, IRL). Considering a drop out rate of about 24% is numerosity you plan to enroll a total of 182 patients in order to obtain 146 patients valid.
3 secondary outcomes
Evaluate the differences between the two drug protocols, in terms of quality of life, by using of the SF-12 questionnaire.
Time frame: 3 months from the enrollment
Evaluation of the differences between the two drug protocols, in the scores obtained in the two sections, functionality and rigidity of the WOMAC questionnaire.
Time frame: 3 months from the enrollment
The evaluation of the attentive functions (selective and divided attention) and of eye-manual coordination and of psycho-motor speed will be performed trough Trail Making Test (Reitan, 1944) to all patients enrolled for the project.
Time frame: 3 months from the enrollment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2017.
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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.
Massimo Allegri, MD principal investigator
IRCCS Fondazione San Matteo Pavia
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Codeine/paracetamol and Oxycodone/naloxone in people with Chronic Pain, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 14 sites in Italy.
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 12 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: withdrawn, as of the sponsor's last update on 19 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Italy. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 withdrawn before enrolling participants, so there are no results.
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?
Evaluate differences in terms of efficacy and tolerability between two pharmaceutical protocols in patients with chronic pain due to osteoarthritis. (time frame: 15 days from the enrolment). 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 19 Apr 2017.