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PainPhase 3KEPALNCT01326325

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

A Phase 3 study testing Ketamine and NaCl in people with Pain, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pain
What is being tested?
Ketamine and NaCl
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
1 siteFrance
Study dates
Jul 2011to Jun 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Ketamine contraindications
  • Methadone or other NMDA-antagonist treatment
  • Karnofsky index under 10
  • Pregnancy

Trial locations and contacts

1 site in 1 country.

France1 site

  • Center of Evaluation and Treatment of the pain - Saint-Antoine Hospital

    Paris, Île-de-France Region, 75012

Other trials in France

About this study

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

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.

Read the 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).

Conditions
Pain
Being tested
Ketamine, NaCl
Keywords
Cancer, Refractory pain, Uncontrolled pain, Ketamine
Medical subject headings
Pain, Neoplasms, Pain, Intractable

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KetamineDrug

    Drip continues of ketamine in intravenous injection included posology enters 0,5mg/kg /day and 2mg/kg/day during 4 days

  • NaClDrug

    Drip continues of NaCl 0,9% in intravenous injection during 4 days

Study groups in NCT01326325
Study groupRoleWhat they receive
KetamineExperimentalKetamine PANFARMA
Receives: Drug: Ketamine
Not KetaminePlacebo comparatorNaCl
Receives: Drug: NaCl

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 4 days

Secondary outcomes (5)

  1. Patient Global Impression of Change/ Clinical Global Impression of Change

    Measured: 4 days

  2. Daily sleep interference score

    Measured: 4 days

  3. Patient satisfaction of pain relief

    Measured: 4 days

  4. Opioids consumption

    Measured: 4 days

  5. Evaluate the adverse effects of opioids-ketamine association versus opioids-placebo

    Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Measured: 4 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionFeb 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01326325
Sponsor's protocol ID
P081242
Acronym
KEPAL
Status last verified
Aug 2013
First submitted
22 Mar 2011
Last updated
7 Aug 2013
Results posted
No
Data monitoring committee
No

Publications

  • DOMINO EF, CHODOFF P, CORSSEN G. PHARMACOLOGIC EFFECTS OF CI-581, A NEW DISSOCIATIVE ANESTHETIC, IN MAN. Clin Pharmacol Ther. 1965 May-Jun;6:279-91. doi: 10.1002/cpt196563279. No abstract available.

    PubMed 14296024

  • Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth. 1981 Jan;53(1):27-30. doi: 10.1093/bja/53.1.27.

    PubMed 7459184

  • Yamamura T, Harada K, Okamura A, Kemmotsu O. Is the site of action of ketamine anesthesia the N-methyl-D-aspartate receptor? Anesthesiology. 1990 Apr;72(4):704-10. doi: 10.1097/00000542-199004000-00021.

    PubMed 1969718

  • Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature. 1994 Feb 17;367(6464):607-14. doi: 10.1038/367607a0.

    PubMed 7509043

  • Jacox A, Carr DB, Payne R. New clinical-practice guidelines for the management of pain in patients with cancer. N Engl J Med. 1994 Mar 3;330(9):651-5. doi: 10.1056/NEJM199403033300926. No abstract available.

    PubMed 7508094

  • Krakowski I, Theobald S, Balp L, Bonnefoi MP, Chvetzoff G, Collard O, Collin E, Couturier M, Delorme T, Duclos R, Eschalier A, Fergane B, Larue F, Magnet M, Minello C, Navez ML, Richard A, Richard B, Rostaing-Rigattieri S, Rousselot H, Santolaria N, Torloting G, Toussaint S, Vuillemin N, Wagner JP, Fabre N; FNCLCC. Summary version of the Standards, Options and Recommendations for the use of analgesia for the treatment of nociceptive pain in adults with cancer (update 2002). Br J Cancer. 2003 Aug;89 Suppl 1(Suppl 1):S67-72. doi: 10.1038/sj.bjc.6601086. No abstract available.

    PubMed 12915905

  • Rostaing-Rigattieri S, Rousselot H, Krakowski I, Theobald S, Collin E, Vuillemin N, Balp L, Torloting G, Fergane B, Richard B, Duclos R, Eschalier A, Delorme T, Minello C, Toussaint S, Richard A, Magnet M, Chvetzoff G, Larue F, Navez ML, Collard O, Bonnefoi MP, Couturier M, Santolaria N, Wagner JP, Fabre N. [Standards, options and recommendations for the use of medical analgesics for the treatment of pain arising from excess nociception in adults with cancer (update 2002): opioid analgesics with the exception of morphine by mouth and the rotation]. Bull Cancer. 2003 Aug-Sep;90(8-9):795-806. French.

    PubMed 14609771

  • Eide PK, Stubhaug A, Stenehjem AE. Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation. Neurosurgery. 1995 Dec;37(6):1080-7. doi: 10.1227/00006123-199512000-00007.

    PubMed 8584148

  • Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain. 1994 Jan;56(1):51-57. doi: 10.1016/0304-3959(94)90149-X.

    PubMed 8159441

  • Max MB, Byas-Smith MG, Gracely RH, Bennett GJ. Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain with allodynia: a double-blind comparison to alfentanil and placebo. Clin Neuropharmacol. 1995 Aug;18(4):360-8. doi: 10.1097/00002826-199508000-00008.

    PubMed 8665549

  • Felsby S, Nielsen J, Arendt-Nielsen L, Jensen TS. NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride. Pain. 1996 Feb;64(2):283-291. doi: 10.1016/0304-3959(95)00113-1.

    PubMed 8740606

  • Nikolajsen L, Hansen CL, Nielsen J, Keller J, Arendt-Nielsen L, Jensen TS. The effect of ketamine on phantom pain: a central neuropathic disorder maintained by peripheral input. Pain. 1996 Sep;67(1):69-77. doi: 10.1016/0304-3959(96)03080-1.

    PubMed 8895233

  • Eide PK, Stubhaug A. Relief of glossopharyngeal neuralgia by ketamine-induced N-methyl-aspartate receptor blockade. Neurosurgery. 1997 Aug;41(2):505-8. doi: 10.1097/00006123-199708000-00043.

    PubMed 9257324

  • Kanamaru T, Saeki S, Katsumata N, Mizuno K, Ogawa S, Suzuki H. [Ketamine infusion for control of pain in patients with advanced cancer]. Masui. 1990 Oct;39(10):1368-71. Japanese.

    PubMed 2255043

  • Oshima E, Tei K, Kayazawa H, Urabe N. Continuous subcutaneous injection of ketamine for cancer pain. Can J Anaesth. 1990 Apr;37(3):385-6. doi: 10.1007/BF03005598. No abstract available.

    PubMed 2322977

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ketamine and NaCl in people with Pain, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: 4 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01326325, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2013.

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