Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients

Ketamine Clinical Trial

— CIVIK  

Official title:

A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients With Refractory Cancer Pain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03362073
• Other study ID #: CIVIK
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2021
• Source: Pusan National University Yangsan Hospital
• Contact: Kwonoh Park, MD, PhD
• Phone: +82-10-3378-3529
• Email: parkkoh[@]daum.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To establish the role of ketamine in hospitalized terminally ill cancer patients with refractory cancer pain, using continuous intravenous infusion of ketamine

Description:

• There are approximately 20 percent patients of refractory cancer pain, which is troubled with uncontrolled pain though treatment including opioids.

• Ketamine has been showed the performance of Ketamine, N-methyl-D-aspartate (NMDA) receptor blocker, in refractory cancer pain based on prior studies.

• We cannot yet confirm the role of Ketamine comparing the benefit and risk due to incompatible results of prior studies. Additionally, most of prior studies were studied in heterogenous groups, which are from beginning of palliative chemotherapy to terminal status, so role of ketamine was not assessed in homogeneous terminally ill cancer patients. And they has used mostly 'bolus intravenous infusion' or 'continuous subcutaneous infusion (CSCI)', relatively rare in continuous intravenous infusion (CIVI).

• The bolus intravenous method is convenient but is concerned with leading to relatively severe adverse events due to poor general condition of terminally ill cancer patients, the CSCI method is not recommended because of adverse events (AEs) such as skin irritation. On the contrary, the CIVI method using gradual increasing ketamine minimizes AEs and is free of skin irritation. Most of hospitalized terminally ill cancer patients has proper IV access using intravascular devices (chemoport or PICC). So, CIVI method is suitable to hospitalized terminally ill cancer patients.

• This study assess the efficacy and safety of 5-days CIVI gradual dose titration of Ketamine in terminally ill cancer patients with refractory cancer pain.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Among patients with histologically or cytologically confirmed malignancy, patients with expected survival time of several months or less due to a progressive disease without additional anticancer treatment.

2. Patients with refractory cancer pain, which cases of requesting 4 or more breakthrough analgesics or increase of baseline analgesics (average pain score = 4 or Personalized pain goal) in spite of 120 mg/day or more of intravenous Morphine Equivalent Daily Dose

3. Hospitalized patients with intravascular access during at least 5 days

4. Age 18 or older

5. Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed about all pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

1. Patients who were treated with ketamine for pain control within 6 months

2. Patients who have been treated with radiotherapy within 4 weeks or plan to intervention for pain control during study period

3. Cancer pain cannot be excluded the Opioid induced hyperalgesia

4. Concomitant severe medical, surgical, or disease or problems which were contraindicated to application of Ketamine or have possibilities of unexpected medical problems caused be the Ketamine

• confirmed or assumed central nervous system lesion which lead to increased intracranial pressure

• Arrhythmia (supra-ventricular tachycardia, ventricular arrhythmia (frequent premature ventricular contraction, bigeminy, Ventricular tachycardia)

• history of hemorrhagic stroke or seizure within 3 months

Related Conditions & MeSH terms

• Cancer Pain
• Ketamine
• Refractory Cancer Pain

Intervention

Drug:
• Ketamine
Application of ketamine using continuous intravenous infusion method during 5 days Ketamine 100mg/2ml + 5% Dextrose water or Normal saline 98 ml mixed fluid Dose schedule: 0.05mg/kg/hr -> 0.10mg/kg/hr -> … -> 0.5mg/kg/hr (increase dose at a rate of 0.05mg/kg/hr every 8 hours)

Locations

Country	Name	City	State
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan	Gyeongsangnam-do

Sponsors (1)

Lead Sponsor	Collaborator
Pusan National University Yangsan Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2017 Jun 28;6:CD003351. doi: 10.1002/14651858.CD003351.pub3. Review. — View Citation

Hanks GW, Justins DM. Cancer pain: management. Lancet. 1992 Apr 25;339(8800):1031-6. Review. — View Citation

Hardy J, Quinn S, Fazekas B, Plummer J, Eckermann S, Agar M, Spruyt O, Rowett D, Currow DC. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. J Clin Oncol. 201 — View Citation

Jackson K, Ashby M, Martin P, Pisasale M, Brumley D, Hayes B. "Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients. J Pain Symptom Manage. 2001 Oct;22(4):834-42. — View Citation

Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage. 2000 Oct;20(4):246-52. — View Citation

van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007 Sep;18(9):1437-49. Epub 2007 Mar 12. Review. — View Citation

Zech DFJ, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain. 1995 Oct;63(1):65-76. doi: 10.1016/0304-3959(95)00017-M. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	complete pain response plus partial pain response; Complete pain response is defined as patient reported pain score using numerical rating scale (range 1-10) = 3 or = personalized pain goal (PPG) and receiving less than four rescue analgesic doses for 24 hours, without unacceptable toxicities; Partial pain response is defined as receiving less than four rescue analgesic doses per day without a patient reported pain score using numerical rating scale (range 1-10) = 3 or = personalized pain goal for 24 hr, without unacceptable toxicities	From date of enrollment until 5 days or drop-out, assess up to 2 years
Secondary	Change of pain intensity	Delineate changes of pain intensity daily, from the time baseline until 5th days after application of ketamine.; Pain intensity is defined as the mean of terdiurnal checked patient reported pain score during a day.	From date of enrollment until 5 days or drop-out, assess up to 2 years
Secondary	Rescue analgesics for breakthrough pain	Dose and number of rescue analgesics for breakthrough pain	From date of enrollment until 5 days or drop-out, assess up to 2 years
Secondary	Patient's satisfaction about Ketamine by a newly developed question in this study	Satisfaction about pain control and Ketamine-related distress during application of ketamine was evaluated by questions as follows: "How do you feel satisfaction about ketamine?" (at 5th days or drop-out)	at the 5th days or drop-out, assess up to 2 years
Secondary	Guardian's satisfaction about Ketamine by a newly developed question in this study	Satisfaction about pain control and Ketamine-related distress during application of ketamine was evaluated by questions as follows: "How do you feel satisfaction about ketamine?" (at 5th days or drop-out)	at the 5th days or drop-out, assess up to 2 years
Secondary	Rate of Ketamine-related adverse events	Rate of Ketamine-related adverse events	From date of enrollment until 5 days or drop-out, assess up to 2 years
Secondary	Rate of early discontinuation	Rate of discontinuation due to Ketamine related AEs	From date of enrollment until 5 days or drop-out, assess up to 2 years
Secondary	Overall survival	Time from application of ketamine until death or discharge/transfer	From date of enrollment until death or discharge/transfer, assess up to 2 years