A Randomized Controlled Trial Study to Assess the Effectiveness and Safety of Methadone Versus Placebo for the Control of Neuropathic Pain in Different Etiologies
Overview
- Phase
- Phase 3
- Intervention
- methadone tablets
- Conditions
- Neuropathic Pain
- Sponsor
- University of Sao Paulo
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Pain intensity change from baseline, assessed by the visual analogue scale (VAS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
Opioids are currently ranked as third-line agents for neuropathic pain (NP) treatment. The opioids more frequently tested for NP were tramadol, oxycodone and morphine. In the present study test the safety and effectiveness of methadone in patients with NP who remain symptomatic despite the use of first and second line drugs in a placebo-controlled randomized approach.
Detailed Description
Background: neuropathic pain (NP) is highly refractory and it is estimated that about 40% of patients remain symptomatic despite the use of first and second line drugs. Opioids are currently ranked as third-line agents for NP treatment. The opioids more frequently tested for NP were tramadol, oxycodone and morphine. In the present study test the effectiveness and safety of methadone, an opioid agonist and glutamate n-methyl-d-aspartate (NMDA) receptor antagonist in patients with NP who remain symptomatic despite the use of first and second line drugs in a placebo-controlled randomized approach. Patients and Methods: this is a randomized, placebo controlled superiority trial including 80 subjects, aged between 18 and 85 years, with NP, that will be randomized to receive methadone or placebo in a 1:1 ratio. Enrollment will take place at the Pain Center of the University of São Paulo and it will include patients from primary care clinics from an area of 2 million people addressed to specialized care at a referral center. Expected results: the study hypothesis is that methadone is superior to placebo and it is safe to use that medication in patients with neuropathic pain. Recruitment time will be extended by 12 months due to dropouts related to the Covid pandemic. We have had dropouts due to a few patients developing covid and also due to patients having fear to become infected while attending hospital visits
Investigators
Daniel Ciampi Araujo de Andrade, MD, PhD
Professor
University of Sao Paulo
Eligibility Criteria
Inclusion Criteria
- •Presence of an exclusive neuropathic pain (without other main pain syndrome occurring concomitantly at the same body area);
- •Pain lasting at least 6 months (chronic) and being present most of the days;
- •Pain fulfilling the current IASP (The International Association for the Study of Pain) criteria for defined Neuropathic Pain and with a score on the DN4 questionnaire (Douleur Neuropathique Pain 4 Questions) ≥ 4 (positive);
- •The pain must be of at least moderate intensity (score on a visual analogue pain scale ≥ 40/100) despite the use of first and second line drugs in an adequate dosing.
Exclusion Criteria
- •Patients under the age of 18 or over 85;
- •Who has neuropathic pain duration less than 6 months;
- •Who do not have an exclusive neuropathic pain (without other main pain syndrome occurring concomitantly at the same body area);
- •Patients with neuropathic pain intensity less than 40 out of 100 on a visual analogue pain scale;
- •Who scored less than 4 on the DN4 scale;
- •Who wishes at any time to abandon the study;
- •Patients with a previous allergic reaction to any of the drugs involved in the study (methadone) or placebo components;
- •Patients in current use or in the last 14 days of medication (s) inhibitor (s) of monoamine oxidase (MAOI) or other medications with potential drug interaction with methadone;
- •Patients in current continuous use of opioids (including methadone);
- •Patients with a history of opioid abuse;
Arms & Interventions
methadone
In this arm patients will take methadone 5mg
Intervention: methadone tablets
placebo
In this arm patients will take placebo tablets (the same number, color and physical aspects as the methadone tablets).
Intervention: Placebo
Outcomes
Primary Outcomes
Pain intensity change from baseline, assessed by the visual analogue scale (VAS)
Time Frame: 0 and 56 days
To evaluate the analgesic effect of methadone (number of patients with ≥ 30% pain intensity change from baseline) compared to placebo in patients with neuropathic pain (NP) of different etiologies. The impact on the average change in the intensity of NP (baseline) will be evaluated, with the main objective being a higher number of responders in the methadone at study completion compared to the placebo group. Responder is defined as pain intensity reduction greater than or equal to 30% compared to the baseline intensity of NP. It will be measured according to a visual analogue scale (VAS), 100 mm long, anchored by two verbal descriptors (0 mm being the total absence of pain and 100 mm being the worst imaginable pain). The measurement of the average change in the intensity of NP (baseline) will be performed by comparing the value on the first visit (day 0) with the value on the final visit (day 56).
Incidence of Serious Treatment-Emergent Adverse Events assessed by a questionnaire
Time Frame: 56 days
The Incidence of Serious Treatment-Emergent Adverse Events will be assessed by measuring the number of participants who experience Serious Adverse Events with the use of methadone or placebo. The search for the adverse events will be done with a questionnaire containing the main adverse events previously described in the medical literature and in the manufacturer's label (methadone). In addition, unexpected adverse events will also be described in detail and reported to the responsible institution. The definition of a serious treatment adverse event will be made in accordance with the rules of the National System of Notifications for Health Surveillance-NOTIVISA. Each serious adverse event will be described in detail and notified to the responsible institution.The comparison between the incidence of Serious Treatment-Emergent Adverse Events will be made between the groups (methadone and placebo) at the end of the study.
Incidence of methadone addiction/misuse or withdrawal syndrome assessed by a prespecified questionnaire
Time Frame: 56 days
The incidence of methadone addiction/misuse or withdrawal syndrome will be assessed by a prespecified questionnaire, containing eight clinical characteristics that may be related to the methadone addition/misuse or withdrawal syndromes. If one or more of those 8 characteristics listed in the questionnaire are present, an immediate communication will be made to the assistant physician (for diagnostic confirmation and referral to multidisciplinary treatment), as well as the exclusion of the individual from the study (after discussion with the research coordinators).
Secondary Outcomes
- Incidence of drop-outs due to Non-Serious Treatment-Emergent Adverse Events assessed by a questionnaire(56 days)