Treatment of Chronic Pain From Osteoarthritis

NCT ID: NCT02032927

Last Updated: 2017-04-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2015-06-30

Brief 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 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.

Conditions

Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Codeine/paracetamol

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.

Group Type: ACTIVE_COMPARATOR

Codeine/paracetamol

Intervention Type: DRUG

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/Naloxone

Combination oxycodone /naloxone, 5 mg/2.5 mg, 1 tablet/day, paracetamol 500 mg if NRS\> 4, repeatable up to 3 times per day.

Group Type: ACTIVE_COMPARATOR

Oxycodone/naloxone

Intervention Type: DRUG

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.

Interventions

Codeine/paracetamol

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.

Intervention Type: DRUG

Oxycodone/naloxone

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Massimo Allegri

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Massimo Allegri, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Fondazione San Matteo Pavia

Locations

Fondazione IRCCS Policlinico San Matteo

Pavia, Pavia, Italy

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, , Italy

Azienda Istituti Ospitalieri di Cremona, Presidio Ospedaliero di Cremona - U.O. di Anestesia, Analgesia e Medicina Perioperatoria

Cremona, , Italy

Azienda Ospedaliera della provincia di Lodi Dipartimento emergenza urgenza

Lodi, , Italy

Azienda Ospedaliera Istituto Ortopedico Gaetano Pini - U.O.C. Anestesia e Rianimazione

Milan, , Italy

Azienda Ospedaliera della Provincia di Pavia - Ospedale Asilo Vittoria di Mortara - U.O. di Pneumotisiologia

Mortara, , Italy

Clinica San Carlo - Casa di Cura Polispecialistica S.p.A. - Unità di Terapia del Dolore

Paderno Dugnano, , Italy

Azienda Servizi alla Persona, ASP, "II.AA.RR." - Istituto di Riabilitazione "Santa Margherita" - Struttura Complessa di Riabilitazione

Pavia, , Italy

Fondazione Salvatore Maugeri - sede di Via Boezio - UO Cure Palliative e Terapia del Dolore

Pavia, , Italy

IRCCS Istituto Clinico "Humanitas" - Anestesia, Day Hospital chirurgico - Chronic Pain Service

Rozzano, , Italy

Dipartimento Integrato di Lungassistenza Anziani - ASL TO1

Torino, , Italy

Ospedale di circolo Fondazione Macchi - SSD Anestesia Day Surgery

Varese, , Italy

Azienda Ospedaliera della Provincia di Pavia - Ospedale Civile di Vigevano - Servizio di Anestesia e Rianimazione

Vigevano, , Italy

Azienda Ospedaliera della Provincia di Pavia - Ospedale Civile di Voghera- U.O. di Medicina Interna - U.O. di Riabilitazione specialistica

Voghera, , Italy

Countries

Italy

Other Identifiers

PT-SM-14-OA

Identifier Type: -

Identifier Source: org_study_id