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Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients (CIVIK)

Primary Purpose

Ketamine, Refractory Cancer Pain

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Ketamine
Sponsored by
Pusan National University Yangsan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ketamine focused on measuring Ketamine, Refractory cancer pain, Terminally ill cancer patients, Palliative care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pusan National University Yangsan HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketamine

Arm Description

continuous intravenous infusion of ketamine

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Rescue analgesics for breakthrough pain
Dose and number of rescue analgesics for breakthrough pain
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)
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)
Rate of Ketamine-related adverse events
Rate of Ketamine-related adverse events
Rate of early discontinuation
Rate of discontinuation due to Ketamine related AEs
Overall survival
Time from application of ketamine until death or discharge/transfer

Full Information

First Posted
November 15, 2017
Last Updated
September 27, 2021
Sponsor
Pusan National University Yangsan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03362073
Brief Title
Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pusan National University Yangsan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketamine, Refractory Cancer Pain
Keywords
Ketamine, Refractory cancer pain, Terminally ill cancer patients, Palliative care

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Prospective, Single institution, Open-label, Phase 2
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketamine
Arm Type
Experimental
Arm Description
continuous intravenous infusion of ketamine
Intervention Type
Drug
Intervention Name(s)
Ketamine
Intervention Description
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)
Primary Outcome Measure Information:
Title
Overall response rate
Description
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
Time Frame
From date of enrollment until 5 days or drop-out, assess up to 2 years
Secondary Outcome Measure Information:
Title
Change of pain intensity
Description
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.
Time Frame
From date of enrollment until 5 days or drop-out, assess up to 2 years
Title
Rescue analgesics for breakthrough pain
Description
Dose and number of rescue analgesics for breakthrough pain
Time Frame
From date of enrollment until 5 days or drop-out, assess up to 2 years
Title
Patient's satisfaction about Ketamine by a newly developed question in this study
Description
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)
Time Frame
at the 5th days or drop-out, assess up to 2 years
Title
Guardian's satisfaction about Ketamine by a newly developed question in this study
Description
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)
Time Frame
at the 5th days or drop-out, assess up to 2 years
Title
Rate of Ketamine-related adverse events
Description
Rate of Ketamine-related adverse events
Time Frame
From date of enrollment until 5 days or drop-out, assess up to 2 years
Title
Rate of early discontinuation
Description
Rate of discontinuation due to Ketamine related AEs
Time Frame
From date of enrollment until 5 days or drop-out, assess up to 2 years
Title
Overall survival
Description
Time from application of ketamine until death or discharge/transfer
Time Frame
From date of enrollment until death or discharge/transfer, assess up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kwonoh Park, MD, PhD
Phone
+82-10-3378-3529
Email
parkkoh@daum.net
First Name & Middle Initial & Last Name or Official Title & Degree
Mikyung Kang
Email
tesoon@hanmail.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kwonoh Park, MD, PhD
Organizational Affiliation
Pusan National University Yangsan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
State/Province
Gyeongsangnam-do
ZIP/Postal Code
50612
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kwonoh Park, MD, PhD
Phone
82+-10-3378-3529
Email
parkkoh@daum.net
First Name & Middle Initial & Last Name & Degree
So Yeon Oh
First Name & Middle Initial & Last Name & Degree
Sang-Bo Oh
First Name & Middle Initial & Last Name & Degree
Eun-Ju Park

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17355955
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. doi: 10.1093/annonc/mdm056. Epub 2007 Mar 12.
Results Reference
result
PubMed Identifier
8577492
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.
Results Reference
result
PubMed Identifier
1349061
Citation
Hanks GW, Justins DM. Cancer pain: management. Lancet. 1992 Apr 25;339(8800):1031-6. doi: 10.1016/0140-6736(92)90546-f. No abstract available.
Results Reference
result
PubMed Identifier
22965960
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. 2012 Oct 10;30(29):3611-7. doi: 10.1200/JCO.2012.42.1081. Epub 2012 Sep 10.
Results Reference
result
PubMed Identifier
11576800
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. doi: 10.1016/s0885-3924(01)00340-2.
Results Reference
result
PubMed Identifier
11027905
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. doi: 10.1016/s0885-3924(00)00194-9.
Results Reference
result
PubMed Identifier
28657160
Citation
Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2017 Jun 28;6(6):CD003351. doi: 10.1002/14651858.CD003351.pub3.
Results Reference
result

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Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients

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