CIVIK: Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients

Sponsor

Pusan National University Yangsan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03362073

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ketamine Refractory Cancer Pain	Drug: Ketamine	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Prospective, Single institution, Open-label, Phase 2Prospective, Single institution, Open-label, Phase 2

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine continuous intravenous infusion of ketamine	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)

Arm

Intervention/Treatment

Experimental: Ketamine

continuous intravenous infusion of ketamine

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)

Outcome Measures

Primary Outcome Measures

Overall response rate [From date of enrollment until 5 days or drop-out, assess up to 2 years]
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

Secondary Outcome Measures

Change of pain intensity [From date of enrollment until 5 days or drop-out, assess up to 2 years]
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.
Rescue analgesics for breakthrough pain [From date of enrollment until 5 days or drop-out, assess up to 2 years]
Dose and number of rescue analgesics for breakthrough pain
Patient's satisfaction about Ketamine by a newly developed question in this study [at the 5th days or drop-out, assess up to 2 years]
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)
Guardian's satisfaction about Ketamine by a newly developed question in this study [at the 5th days or drop-out, assess up to 2 years]
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)
Rate of Ketamine-related adverse events [From date of enrollment until 5 days or drop-out, assess up to 2 years]
Rate of Ketamine-related adverse events
Rate of early discontinuation [From date of enrollment until 5 days or drop-out, assess up to 2 years]
Rate of discontinuation due to Ketamine related AEs
Overall survival [From date of enrollment until death or discharge/transfer, assess up to 2 years]
Time from application of ketamine until death or discharge/transfer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
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
Hospitalized patients with intravascular access during at least 5 days
Age 18 or older
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:

Patients who were treated with ketamine for pain control within 6 months
Patients who have been treated with radiotherapy within 4 weeks or plan to intervention for pain control during study period
Cancer pain cannot be excluded the Opioid induced hyperalgesia
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