Effectiveness of Ketamine in Malignant Neuropathic Pain Relief

This Phase III, randomised, quadruple-masked, placebo-controlled crossover trial (n=20 completers) will evaluate whether adding low-dose ketamine to subcutaneous morphine improves analgesia in hospitalised adults aged 18–70 years with neuropathic cancer pain that remains inadequately controlled despite continuous morphine infusion. Participants will receive ketamine 1 mg/kg per 24 hours or sodium chloride 0.9% as a separate subcutaneous infusion via syringe driver for 48 hours, followed by a wash-out period of at least 10 hours before crossover to the alternative treatment for a further 48 hours. Pain intensity at rest and during movement will be recorded 4 times daily using an 11-point numerical rating scale, with subcutaneous morphine available as rescue medication. The primary outcome is change in pain intensity from baseline over 5 days; adverse effects will also be assessed.
Detailed Description

To see whether the addition of low-dose ketamine to a subcutaneous morphine infusion improves analgesia in patients with neuropathic cancer pain.

Study Arms & Interventions

Ketamine 70 mg/70 kg

active comparator

Ketamine 1 mg per kg per 24 hours as subcutaneous infusion via syringe driver for 48 hours.

Interventions

• Ketamine1 mg/kgvia Subcutaneous• per 24 hours for 48 hours

Placebo (matched to ketamine 70 mg/70 kg)

inactive

Sodium chloride 0.9% administered as a subcutaneous infusion via syringe driver for 48 hours.

Interventions

• Placebovia Subcutaneous• for 48 hours

Participants

Ages

18 – 70

Sexes

Male & Female

BMI

–

Psychosis History

–

Inclusion Criteria

• Age 18-70 years. In-patient. Cancer pain judged to have a neuropathic component. Clinically normal renal and hepatic function. Able to cooperate and understand information. Worst pain at rest or on movement 5 or more (NRS 0-10). Pain currently treated with continuous subcutaneous morphine infusion. The daily morphine dose is 48mg or more per 24 hours and a 30% increase in the daily dose has not provided sufficient pain relief.
• Not treated with ketamine during the last 48 hours prior to inclusion.
• \-

Exclusion Criteria

Pregnant and lactating women. Any situation in which an increase in blood pressure would constitute a hazard. Acute intermittent porphyria. Psychiatric illness, epilepsy, alcoholism, glaucoma. Hypersensitivity to any of the drugs ingredients. Current treatment with ketamine.

Reduced renal or hepatic function. Suspicion of morphine toxicity (sedation, hallucination, myoclonus, increasing pain).

Increased intracranial pressure (suspicion of cerebral metastases) or cerebral metastases.

Unable to cooperate/ understand information. Worst pain at rest or on movement less than 5 on NRS. Current treatment with other opioids than morphine. The patient is undergoing radiotherapy in the pain area, or has received radiotherapy in the pain area within the last four weeks.

Changes in the use of analgesics (paracetamol, NSAIDS), adjuvant drugs (antidepressants, antiepileptic, corticosteroids, muscle relaxants) or their dosages less than 2 days prior to inclusion or during the study period.