Efficacy of Low Analgesic Doses of Ketamine Associated With Opioids in Refractory Cancer Pain Treatment (KEPAL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01326325
First received: March 22, 2011
Last updated: August 6, 2013
Last verified: August 2013
  Purpose

Long-term opioid therapy is commonly administered for the management of severe cancer pain. Increasing doses of opioids are titrated against effects until analgesia is achieved or intolerable adverse effects occur. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been reported to improve analgesia in patients with uncontrolled pain receiving high doses of opioids. This study aims at determining the effectiveness of ketamine as an adjuvant to opioids in relieving cancer pain.


Condition Intervention Phase
Pain
Drug: Ketamine
Drug: NaCl
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of the Efficiency of the Ketamine With Low Analgesic Doses, in Association With High Opioids, in the Treatment of the Rebels Pains, in Palliative Phase of the Cancerous Disease

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • The percentage of reduction of the daily average score of painful intensity after 4 days of treatment (to J4), with regard to the basic value to J0 [ Time Frame: 4 days ] [ Designated as safety issue: No ]
    The daily average score of painful intensity being the score of painful intensity of the previous 24 hours, determined by the patient on a digital scale(ladder) validated from 0 to 10


Secondary Outcome Measures:
  • Patient Global Impression of Change/ Clinical Global Impression of Change [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Daily sleep interference score [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Patient satisfaction of pain relief [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Opioids consumption [ Time Frame: 4 days ] [ Designated as safety issue: No ]
  • Evaluate the adverse effects of opioids-ketamine association versus opioids-placebo [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events as a Measure of Safety and Tolerability


Enrollment: 24
Study Start Date: July 2011
Study Completion Date: June 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
Ketamine PANFARMA
Drug: Ketamine
Drip continues of ketamine in intravenous injection included posology enters 0,5mg/kg /day and 2mg/kg/day during 4 days
Other Name: Ketamine
Placebo Comparator: Not Ketamine
NaCl
Drug: NaCl
Drip continues of NaCl 0,9% in intravenous injection during 4 days
Other Name: NaCl

Detailed Description:

Main objective:

To show that low analgesic doses of ketamine in intravenous infusion during 4 days associated with opioids better relieve refractory cancer pain than opioids without ketamine.

This study is a prospective study, multicenter (11 centres), consisting of 3 phases:

  • a randomized controlled double blind phase of 5 days with 2 parallel groups of 38 patients each : ketamine (in association with high opioids), in intravenous injection during 4 days, versus placebo (in association with high opioids), in intravenous injection during 4 days ;
  • an open-label phase of maximum 4 days, during which the ketamine Panpharma® is administered in intravenous infusion to the hospitalized patients who are still having uncontrolled pain persisting or recurrent ;
  • an observational phase : starting at the discharge of the patient, of a maximal period of 6 months.The inclusion period is during 18 months, the total duration of the study is 2 years.

    76 patients are expected: 38 will be treated with opioids and ketamine; 38 will be treated with opioids and a placebo.

Success is defined by a decrease of the daily pain score of 50 % after 4 days. The expected rate of success in the placebo group is 10 % whereas the expected rate of success in the ketamine group is 30 %.

Primary outcome (pain score on a 11-point numerical scale) will be evaluated everyday as well as secondary outcomes (patient and clinician global impression of change, opioid consumption, adverse reactions, patient satisfaction on pain relief, sleep interference score).

Vital parameters (cardiac frequency, respiratory frequency and arterial blood pressure) will be checked everyday, many times a day : every hour for the four hours after the beginning of the treatment and then, every four hours ; every hour for the two hours following a dose shift).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hospitalized cancer patients (informed and conscious of the cancer diagnostic)
  • Undergoing opioid treatment for 15 days at least
  • Refractory pain (score higher than 5 on an 10-point numerical pain rating scale)
  • Ability to score pain on a numerical pain rating scale
  • Patient written agreement

Exclusion Criteria:

  • Ketamine contraindications
  • Methadone or other NMDA-antagonist treatment
  • Karnofsky index under 10
  • Pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01326325

Locations
France
Center of Evaluation and Treatment of the pain - Saint-Antoine Hospital
Paris, Ile de France, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Sylvie ROSTAING-RIGATTIERI, MD Center of Evaluation and Treatment of the pain - Saint-Antoine Hospital
  More Information

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01326325     History of Changes
Other Study ID Numbers: P081242
Study First Received: March 22, 2011
Last Updated: August 6, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Cancer
Refractory pain
Uncontrolled pain
Ketamine

Additional relevant MeSH terms:
Analgesics
Ketamine
Analgesics, Opioid
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 23, 2014