Development and Evaluation of a Methadone Protocol for Severe Chronic Pain Management

Study Overview
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Brief Summary
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Methadone is a synthetic mu opioid agonist that has been proved as clinically effective in pain management. However, methadone usage for pain control in Thailand has been limited because physicians are not familiar with its dosing and concern about the risk of drug accumulation and cardiac arrhythmia. Therefore, this prospective study was conducted to evaluate the efficacy and safety of a methadone protocol in Thai patients with severe chronic noncancer and cancer pain.

Detailed Description
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Chronic pain is defined as pain that persists beyond normal tissue healing time, which is assumed for 3 months by the IASP. The symptoms include either continuous or intermittent pain, that could be caused by tumor or other multiple etiologies. The consequence of uncontrolled chronic pain presents not only physiologic symptoms but also psychiatric disorders leading to severely impact daily living. In Thailand, the use of methadone for pain management has been limited because physicians are not familiar with its dosing and concern about the risk of drug accumulation and cardiac arrhythmia. Therefore, the aim of this study is to evaluate the efficacy and safety of a protocol of methadone dosing in outpatients with severe chronic pain. Thirty four chronic pain patients will be included to initiate methadone use following the protocol. Pain scores, pain interferences scores, neuropathic pain score, severity of adverse effects, and QTc intervals will be assessed at baseline, and two, four, eight, and twelve weeks after starting methadone. The approved protocol of methadone therapy obtained from this study could be clinically utilized by physicians for severe chronic pain management.

Official Title
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Development and Evaluation of a Methadone Protocol for Severe Chronic Pain Management

Conditions
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Pain, Chronic

Intervention / Treatment
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* Drug: Methadone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients aged 18 or over who suffered from severe chronic cancer or noncancer pain to be firstly treated with methadone as analgesics Exclusion Criteria: QTc interval that was more than 500 msec History of opioid addiction Having structural heart diseases During pregnancy or lactation period Patients who have hypersensitivity to methadone

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: methadone<br>single group | Drug: Methadone<br>* The starting methadone dose for naïve-opioid patients was 2.5-5 mg every 8-12 hours. In patients who required opioid rotation, the conversion ratios, morphine:methadone, were 4:1, 8:1, and 12:1 for patients receiving less than 90 mg of morphine, receiving 90-300 mg of morphine, and receiving more than 300 mg of morphine , respectively. A fixed dose ratio of 1:20 was applied for changing from transdermal fentanyl to oral methadone. Then, the daily calculated methadone dose was divided into 8-12 hourly dosing. Calculated rescue dose was estimated to be 10-15% of total daily dose of methadone which there was switched to be morphine syrup in the ratio of 1:4.<br>* Other names: Methadone GPO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score | pain scores are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain interferences scores | pain interferences scores are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone. | 3 months | 
| severity of adverse effects | severity of adverse effects are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone | 3 months | 
| QTc intervals | QTc intervals are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone | 3 months | 
| Neuropathic pain score | Neuropathic pain score are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methadone, chronic pain, noncancer pain, cancer pain, QTc prolongation