Comparison of Oral Morphine Versus Nasal Ketamine Spray With Chitosan in Cancer Pain Outpatients

Study Overview
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Brief Summary
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34 adult (>18 years) cancer pain outpatients with Opioid base therapy because of pain and breakthrough pain or extreme pain on movement will be included in this prospective, randomized, double-blind crossover study. Over a period of 3 weeks patients will go through 3 treatment arms, each one lasting one week: Group A receives morphine drops and Placebo spray, Group B receives ketamine/chitosan spray nasal and Placebo drops and Group C receives morphine drops and ketamine/chitosan spray nasal. Primary endpoint is time to onset of action of intranasal ketamine compared with morphine drops. Secondary endpoint is the median numeric rating scale (NRS) improvement after using the spray or morphine or the combination of ketamine spray and morphine drops.

Official Title
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Comparison of Oral Morphine Versus Nasal Ketamine Spray With Chitosan in Cancer Pain Outpatients

Conditions
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Cancer: Breakthrough Pain, Cancer: Extreme Pain on Movement

Intervention / Treatment
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* Drug: Morphine
* Drug: Ketamine
* Drug: Placebo
* Drug: Chitosan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer pain in outpatients with: Opioid based therapy due to pain Breakthrough pain or Extreme pain on movement Age >= 18 years Exclusion Criteria: Patients unable to give written informed consent Patients unable to understand how to handle and document the use of the study medication Known drug allergies or intolerance to ketamine Known drug allergies or intolerance to morphine Known allergy to crustacea or chitosan Patients using snuff at a regular basis Recreational drug addiction or abuse Serious intranasal or epipharyngeal Problems (Septum wall defects, cancer) Mental/psychiatric disorder Patients with renal failure (clearance < 30 ml/min) Pregnancy and breast feeding mothers Patients not understanding German Patient having arterial hypertonia with measured values > 180/95

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: morphine drops solo and placebo spray<br>morphine 2% drops daily fixed dose of morphine equivalents < 100 mg, 0.2 mg/kg Body weight morphine drops every hour in reserve due to international Standards daily fixed dose of morphine equivalents =/> 100 mg, 15% of the fixed daily dose in morphine drops every hour in reserve due to international standards | Drug: Morphine<br> <br> Drug: Placebo<br> <br> |
| Other: ketamine/chitosan spray nasal and placebo drops<br>5 mg ketamine all 5 minutes, maximal 4 times an hour | Drug: Ketamine<br> <br> Drug: Placebo<br> <br> Drug: Chitosan<br> <br> |
| Other: morphine drops and ketamine/chitosan spray nasal<br>see above | Drug: Morphine<br> <br> Drug: Ketamine<br> <br> Drug: Chitosan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of action of intranasal ketamine compared with morphine drops |  | 5 minutes | 
| Time to onset of action of intranasal ketamine compared with morphine drops |  | 10 minutes | 
| Time to onset of action of intranasal ketamine compared with morphine drops |  | 15 minutes | 
| Time to onset of action of intranasal ketamine compared with morphine drops |  | 20 minutes | 
| Time to onset of action of intranasal ketamine compared with morphine drops |  | 45 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median NRS improvement after using the spray or morphine or the combination of ketamine spray and morphine drops |  | after 5, 10, 15, 20, 45 minutes | 
| Total amount of delivered applications of ketamine or morphine in each study arm |  | 3 weeks | 
| Total amount of fixed and reserve opioid doses increase in each study arm |  | 3 weeks | 
| Assessment of Nausea, vomiting, itching, fatigue, hallucinations, Irritation of nasal mucosa |  | 3 weeks |