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

Pain, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02335398
• Other study ID #: 289/2554(EC4)
• Status: Completed
• Phase: Phase 4
• First received: January 7, 2015
• Last updated: January 7, 2015
• Start date: July 2011
• Est. completion date: December 2013

Study information

• Verified date: January 2015
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ethical Committee
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Pain
• Pain, Chronic

Intervention

Drug:
• Methadone
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.

Locations

Country	Name	City	State
Thailand	Siriraj Hospital	Bangkoknoi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (5)

Bruera E, Sweeney C. Methadone use in cancer patients with pain: a review. J Palliat Med. 2002 Feb;5(1):127-38. Review. — View Citation

Mercadante S, Casuccio A, Calderone L. Rapid switching from morphine to methadone in cancer patients with poor response to morphine. J Clin Oncol. 1999 Oct;17(10):3307-12. — View Citation

Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P, Gebbia V, Ripamonti C. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncol. 2001 Jun 1;19(11):2898-904. — View Citation

Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmacoepidemiol Drug Saf. 2005 Nov;14(11):747-53. — View Citation

Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F. Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? J Clin Oncol. 1998 Oct;16(10):3216-21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain score	pain scores are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone.	3 months	No
Secondary	pain interferences scores	pain interferences scores are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone.	3 months	No
Secondary	severity of adverse effects	severity of adverse effects are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone	3 months	Yes
Secondary	QTc intervals	QTc intervals are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone	3 months	Yes
Secondary	Neuropathic pain score	Neuropathic pain score are assessed at baseline, and two, four, eight, and twelve weeks after starting methadone	3 months	No