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

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.

Study Overview

• Status: Terminated
• Conditions: Cancer: Breakthrough Pain; Cancer: Extreme Pain on Movement
• Intervention / Treatment: Drug: Placebo; Drug: Morphine; Drug: Ketamine; Drug: Chitosan

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Pain Relief Unit and Anaesthesiology, University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: morphine drops solo and placebo spray; 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: Placebo; Drug: Morphine
Other: ketamine/chitosan spray nasal and placebo drops; 5 mg ketamine all 5 minutes, maximal 4 times an hour	Drug: Placebo; Drug: Ketamine; Drug: Chitosan
Other: morphine drops and ketamine/chitosan spray nasal; see above	Drug: Morphine; Drug: Ketamine; Drug: Chitosan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Wilhelm Ruppen, PD Dr. med., Pain Relief Unit and Anaesthesiology, University Hospital Basel, Switzerland

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 6, 2017

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Actual): November 13, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Breakthrough Pain; Cancer Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Analgesics, Opioid; Narcotics; Hemostatics; Coagulants; Chelating Agents; Sequestering Agents; Ketamine; Morphine; Chitosan
• Other Study ID Numbers: EKNZ 2014-249