A randomised controlled trial in the palliative setting regarding off-label medication: investigating the efficiency of amitriptyline versus pregabalin from a societal perspective
Projectomschrijving
Neuropathische pijn, in de volksmond zenuwpijn, is een brandende, zeurende, of tintelende pijn die wordt veroorzaakt door een zenuw. Bij patiënten met kanker kan neuropathische pijn ontstaan door de behandeling of doordat de tumor op een zenuw drukt.
Onderzoek
Wij onderzochten welk geneesmiddel het beste werkt met de minste bijwerkingen en kosten: amitriptyline of pregabaline. Het lot besliste met welk medicijn gestart werd. Bij onvoldoende werking kon het andere middel toegevoegd worden, al dan niet met continuering van het oorspronkelijke middel. De patiënt werd gedurende 8 weken gevolgd.
Resultaten
In totaal 52 patiënten zijn gevolgd. Er bleken geen verschillen tussen beide groepen in werking of bijwerkingen tussen beide middelen. Wel waren de medicatiekosten in de groep patiënten die met pregabaline startten 4 keer zo hoog.
Wij, als onderzoekers, durven op grond van dit onderzoek te concluderen dat wij aanraden om bij neuropathische pijn bij kanker te starten met het goedkope amitriptyline.
Verslagen
Eindverslag
Samenvatting van de aanvraag
Introduction: As a consequence of an adaptation of a Dutch law about medication prescription, off-label medication is not allowed anymore unless a standard or protocol exists or if the physician has consulted a pharmacist. Regarding neuropathic pain in incurable cancer patients, pregabalin has been registered for neuropathic non-cancer pain, and amitriptyline is not registered for neuropathic pain at all but is recommended as the drug of first choice in the Dutch handbooks of palliative care.1,2 No clinical trials for this patient group have been published. Objectives: To compare efficiency, side effects and costs of a strategy with amitriptyline as drug of first choice versus a strategy with pregabalin as drug of first choice. Design: An open label, randomised non-inferiority trial Population: Incurable cancer patients with neuropathic pain receiving palliative care Intervention: When a patient agrees to take part in the study and has given informed consent,, he will be allocated randomly to one of the two study groups. A minimisation randomisation algorithm will be used, that balances for type of pain (nociceptive versus others), type of palliative treatment (chemotherapy, radiotherapy) and physician. Each drug will be dosed in a step up titration procedure. Patients will be followed during 8 weeks. Sample size calculation: Based on the literature on pain in non-cancer patients, we presume that both drugs are equivalent regarding pain reduction and side effects. Sample size calculation: As amitriptyline is cheaper, the aim is to show that in the amitriptyline arm, pain control is comparable to the pain control in the pregabalin arm, or at least not relevantly less. Based on a difference of 1 cm on the VAS-I between the treatments and a non-inferiority margin of 0.25 cm, 130 patients (of which 120 evaluable) are required for 80% power. Outcome measures: Mean current pain, as measured three times daily with the VAS-I of the McGill questionnaire, costs, side effects, quality of life, number of drugs prescribed to relief pain (including escape drugs) and medication compliance.