Duloxetine and Pregabalin for Neuropathic Cancer Pain
A Phase III, international, multi-centre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin over 14 days for cancer-related neuropathic pain.
University of Technology Sydney
84 participants
Nov 29, 2022
Interventional
Conditions
Summary
This study aims to evaluate the effectiveness and safety of duloxetine and pregabalin for neuropathic cancer pain. Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have a diagnosis of cancer and neuropathic pain. Study details Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will take an oral dose of the drug, Duloxetine, twice daily for 14 days. Participants in the other group will take twice daily oral pregabalin instead. Participants and the research team will be blinded to the treatment and will not know which treatment, Duloxetine or Pregabalin, has been allocated. The Duloxetine/Pregabalin dose will be gradually increased over 7 days. The maximal tolerated dose will be continued until Day 14. On Day 14, participants will have the option to be unblinded and find out the treatment they were allocated if they choose to continue on that same treatment. Those who do not wish to continue on the same treatment will not be unblinded at Day 14 and will gradually taper down the dose over the next 7 days and cease the study medication. These participants may then be unblinded once the tapering is complete and study medication has been ceased. All participants will be monitored for safety, and toxicity. They will also be asked to complete questionnaires to rate their cancer pain, quality of life, anxiety and depression for up to 21 days. It is hoped that this comparison of benefits and harms between duloxetine and pregabalin will help us to better treat people with neuropathic cancer pain.
Eligibility
Inclusion Criteria10
- Inpatients and outpatients with diagnoses of cancer and neuropathic pain (probable or definite neuropathic pain by IASP criteria).
- Age 18 years or more.
- Able to complete study assessments and comply with the study procedures.
- Ability to provide informed written consent.
- Pain related to cancer with a worst pain score of 4 or greater on BPI item 3 (worst pain intensity) score within 24 hours of baseline.
- Neuropathic Pain on LANSS or s-LANSS of 12 or greater within 7 days of study commencement.
- Taking regular analgesics (e.g opioids, paracetamol, non-steroidal anti-inflammatory drugs, adjuvants).
- If taking regular opioids, the oral morphine equivalent dose must be stable within 48 hours before commencing on the study. If taking methadone, dose must be stable for 72 hours before commencing on the study. Short acting and rapid onset breakthrough-opioids as needed may be used up to 4 doses/day and still be considered ‘stable’.
- If taking any type of regular adjuvant analgesic (e.g., antidepressants, anticonvulsants, antiarrhythmic agents, N-methyl-D-aspartate receptor antagonists, and steroids) other than pregabalin or gabapentin, the dose must be stable for 48 hours prior to commencing on the study.
- Paracetamol and non-steroidal anti-inflammatory drugs must be stable for 48 hours prior to commencing on the study.
Exclusion Criteria15
- Chemotherapy-Induced Peripheral Neuropathy (CIPN) (glove and stocking), post thoracotomy or post breast surgery pain as the primary pain. These are allowed as an additional pain if the patient has another source of neuropathic pain.
- Cauda equina syndrome or spinal cord compression within 4 weeks of baseline. Spinal cord compression which is untreatable or treated at least 4 weeks prior and is on a stable dose of steroids is allowed. Change made after enrolment of 8 participants.
- Contraindication for duloxetine or pregabalin.
- Taking duloxetine for any reason within 2 weeks of baseline.
- Taking pregabalin greater than 50 mg/day for any reason (25 mg per day if the participant has an eGFR 30-50 mL/min/1.73m2) or taking gabapentin greater than 300mg/day for any reason (150mg per day if the participant has an eGFR 30-50 mL/min/1.73m2).
- Taking moclobemide or fluvoxamine or desvenlafaxine or venlafaxine for any reason.
- Taking reversible monoamine oxidase inhibitors (MAOIs)
- Participants who have participated in a clinical trial involving a new chemical entity within four weeks prior to study entry.
- Patients with clinically significant cognitive impairment (clinician defined) causing unreliable completion of study procedures.
- Patients who have a current or recent history of abuse of alcohol, or recent history of substance misuse..
- Patients who are pregnant, breastfeeding or may possibly be pregnant.
- Other patients who are determined to be inappropriate for participation in the study by the clinical investigator.
- Starting a new chemotherapy regimen within 14 days of baseline .
- Patients with renal failure defined as eGFR less than 30ml/min/1.73m2 calculated according to the CKD-EPI formula. For those with a Body Mass Index (BMI) equal to 18, the PI is to individually assess the circumstances of the participant and use an alternative approach to calculate renal function and confirm the absence of renal failure.
- Bilirubin greater than twice the upper limit of normal at baseline.
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Interventions
Duloxetine 30mg/day orally for 7 days, then increase to 60mg/day for 7 days, then downward titrate to 30mg/day for 7 days. Dosing is twice daily (morning and evening dose). Total duration of treatment is up to 21 days, titrate up to maximal dose to primary endpoint at day 14. Option to be unblinded at Day 14 or taper down dose and cease the study medication. Participants who opt to be unblinded can continue on duloxetine in open-label form, obtained by usual access method and supervised by their usual treating clinician. Adherence will be monitored by review of daily dosing record completed by participant (at each contact), and reconciliation of returns.
Locations(13)
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ACTRN12620000656932