Clinical trial NCT01326325: Efficacy of Low Analgesic Doses of Ketamine Associated With Opioids in Refractory Cancer Pain 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Keywords: Cancer
Refractory pain
Uncontrolled pain
Ketamine
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2011-03-30
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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
timeFrame: 4 days
Secondary outcomes:
measure: Patient Global Impression of Change/ Clinical Global Impression of Change
timeFrame: 4 days
measure: Daily sleep interference score
timeFrame: 4 days
measure: Patient satisfaction of pain relief
timeFrame: 4 days
measure: Opioids consumption
timeFrame: 4 days
measure: Evaluate the adverse effects of opioids-ketamine association versus opioids-placebo
timeFrame: 4 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Center of Evaluation and Treatment of the pain - Saint-Antoine Hospital
state: Ile de France
Study officials:
affiliation: Center of Evaluation and Treatment of the pain - Saint-Antoine Hospital
name: Sylvie ROSTAING-RIGATTIERI, MD
role: PRINCIPAL_INVESTIGATOR
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