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

Pain Clinical Trial

— KEPAL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01326325
• Other study ID #: P081242
• Status: Completed
• Phase: Phase 3
• First received: March 22, 2011
• Last updated: August 6, 2013
• Start date: July 2011
• Est. completion date: June 2013

Study information

• Verified date: August 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: French Data Protection Authority
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• Ketamine
Drip continues of ketamine in intravenous injection included posology enters 0,5mg/kg /day and 2mg/kg/day during 4 days
• NaCl
Drip continues of NaCl 0,9% in intravenous injection during 4 days

Locations

Country	Name	City	State
France	Center of Evaluation and Treatment of the pain - Saint-Antoine Hospital	Paris	Ile de France

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (34)

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* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	4 days	No
Secondary	Patient Global Impression of Change/ Clinical Global Impression of Change		4 days	No
Secondary	Daily sleep interference score		4 days	No
Secondary	Patient satisfaction of pain relief		4 days	No
Secondary	Opioids consumption		4 days	No
Secondary	Evaluate the adverse effects of opioids-ketamine association versus opioids-placebo	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	4 days	Yes