Effectiveness of Ketamine in Malignant Neuropathic Pain Relief

NCT01951911 | Withdrawn Phase 3 DMC

• 1 other identifier: 2012/539
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pain, Intractable

Keywords

Pain Management; Ketamine; Palliative care

Outcome Measures

Primary Outcomes (1)

• Change in pain intensity compared to baseline.

  Significant reduction in cancer pain intensity will be defined as at least 30% reduction in Numeric Rating Scale (NRS) score compared to baseline.

  5 days

Study Arms (2)

Ketamine

ACTIVE COMPARATOR

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

Drug: Ketamine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ketamine DRUG

Patients will receive either ketamine as subcutaneous infusion or placebo as subcutaneous infusion. The results will be compared with each other.

Also known as: Ketalar

Ketamine

Placebo DRUG

Also known as: Sodium chloride 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Haukeland University Hospital

Bergen, Hordaland, 5021, Norway

Location

Related Publications (10)

• Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain. 1995 Sep;62(3):259-274. doi: 10.1016/0304-3959(95)00073-2.

  PMID: 8657426 BACKGROUND

• Ko SW, Wu LJ, Shum F, Quan J, Zhuo M. Cingulate NMDA NR2B receptors contribute to morphine-induced analgesic tolerance. Mol Brain. 2008 Jun 17;1:2. doi: 10.1186/1756-6606-1-2.

  PMID: 18803856 BACKGROUND

• Mayer DJ, Mao J, Price DD. The association of neuropathic pain, morphine tolerance and dependence, and the translocation of protein kinase C. NIDA Res Monogr. 1995;147:269-98.

  PMID: 8742791 BACKGROUND

• Qi X, Evans AM, Wang J, Miners JO, Upton RN, Milne RW. Inhibition of morphine metabolism by ketamine. Drug Metab Dispos. 2010 May;38(5):728-31. doi: 10.1124/dmd.109.030957. Epub 2010 Feb 2.

  PMID: 20124399 BACKGROUND

• Bell RF, Eccleston C, Kalso E. Ketamine as adjuvant to opioids for cancer pain. A qualitative systematic review. J Pain Symptom Manage. 2003 Sep;26(3):867-75. doi: 10.1016/s0885-3924(03)00311-7.

  PMID: 12967737 BACKGROUND

• Bell RF. Low-dose subcutaneous ketamine infusion and morphine tolerance. Pain. 1999 Oct;83(1):101-3. doi: 10.1016/s0304-3959(99)00096-2.

  PMID: 10506678 BACKGROUND

• Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006 Oct;22(10):1911-20. doi: 10.1185/030079906X132488.

  PMID: 17022849 BACKGROUND

• Hagelberg NM, Peltoniemi MA, Saari TI, Kurkinen KJ, Laine K, Neuvonen PJ, Olkkola KT. Clarithromycin, a potent inhibitor of CYP3A, greatly increases exposure to oral S-ketamine. Eur J Pain. 2010 Jul;14(6):625-9. doi: 10.1016/j.ejpain.2009.10.003. Epub 2009 Nov 7.

  PMID: 19897389 BACKGROUND

• Nisbet AT, Mooney-Cotter F. Comparison of selected sedation scales for reporting opioid-induced sedation assessment. Pain Manag Nurs. 2009 Sep;10(3):154-64. doi: 10.1016/j.pmn.2009.03.001.

  PMID: 19706353 BACKGROUND

• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

  PMID: 2748771 BACKGROUND

MeSH Terms

Conditions

Pain, Intractable; Agnosia

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Rae F Bell, M.D. PhD.

  Pain Clinic, Haukeland University Hospital, 5021 Bergen, Norway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: September 27, 2013
• Study Start: September 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: July 11, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)