The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam (NASKEMI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01275547
First received: January 11, 2011
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

Introduction

Ketamine is an old and generally well accepted analgesic used in the intra- and perioperative setting. Several studies demonstrated the effectiveness of ketamine in the postoperative setting.

A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m.. None of the volunteers had serious adverse effects or complications. A preliminary data analysis shows a clear analgesic effect and good absorption of the intranasal S-ketamine.

As a next step we would like to investigate the effect of S-ketamine intranasal spray combined with midazolam intranasal spray in a group of postoperative spinal surgery patients. The rational for the combination of intranasal S-ketamine and midazolam is the well known midazolam antagonising effect of ketamine induced psychomimetic adverse effects. Furthermore we know from other studies (EKBB 106/06) that midazolam intranasal spray has relaxant and anxiolytic effects. As far as we know, this is the first study which will examine the combination of S-ketamine and midazolam intranasal sprays in adult patients.

Study work plan

This prospective, randomized, double-blinded non inferiority study will address pain ratings and patient satisfaction in a postoperative setting in two treatment scenarios:

  1. Alternating S-ketamine intranasal unit-dose spray (6 mg per dose) with midazolam intranasal spray (0.75 mg per dose) patient controlled application with a lock-out interval of 20 minutes between two applications and placebo patient controlled analgesia (PCA) with a lock-out interval of 12 minutes with saline 0.9% i.v. for 72 hours or until 40 unit-dose sprays are delivered
  2. PCA with 2 mg morphine with a lock-out interval of 12 minutes i.v. with placebo intranasal spray (saline 0.9% + chitosan) with a minimum lock-out interval of 20 minutes for 72 hours or until 40 unit-dose sprays are delivered

Patient number

We will examine 36 patients, 18 patients in each group. The study duration for an individual patient will be at latest 72 hours, the total study duration is 4 to 5 months.

Study importance

An intranasal spray is an ideal application form for surgery patients, either in- or outpatients. On the other hand, ketamine and S-ketamine is quite often used in the perioperative setting as a rescue analgesic. In higher doses it could be used as an emergency tool in emergency prehospital medicine. In the perioperative setting it is important to evaluate the efficacy and safety of S-ketamine intranasal spray combined with midazolam intranasal spray in patients.

If our study shows that S-ketamine intranasal spray is effective as an analgesic and has good patient acceptance, S-ketamine intranasal spay could be considered as an alternative, completely non-invasive analgesic procedure in a postoperative outpatient setting. As a consequence development of a nasal multidose-applicator combining S-ketamine and midazolam would be of interest.


Condition Intervention Phase
Analgesia, Patient-controlled
Spinal Stenosis
Drug: s-ketamine & midazolam
Drug: Morphine PCA
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: The Analgesic Effect of Combined Treatment With Intranasal S-Ketamine and Intranasal Midazolam Compared With Morphine Patient Controlled Analgesia in Spinal Surgery Patients

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Numeric rating scale 24 hours after surgery [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    NRS after 24 hours after finishing surgery


Secondary Outcome Measures:
  • Amount of PCA boli [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

    Amount of demanded / delivered unit doses of intranasal S-ketamine

    / midazolam or morphine PCA-boli



Enrollment: 22
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: S-ketamine & midazolam spray
all 20 minutes as a patient controlled analgesia alternating s-ketamine / midazolam
Drug: s-ketamine & midazolam
s-ketamine 6 mg intranasal midazolam 0.75 mg intranasal
Active Comparator: morphine, patient controlled analgesia
morphine as an active comparator as a patient controlled analgesia system
Drug: Morphine PCA
2 mg Morphine i.v. all 12 minutes as a patient controlled system

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Spinal surgery patients with:

    • decompression because of spinal stenosis
    • laminectomy because of spinal stenosis
  • Age > 18 years
  • BMI 18 - 39.9 (kg/m2)

Exclusion Criteria:

  • Patients unable to give written informed consent

    • Known drug allergies or intolerance to the study medications morphine, midazolam, ketamine, paracetamol or metamizol
    • Known allergy to crustacea or chitosan
    • Patients using snuff at a regularly basis
    • Recreational drug addiction or abuse
    • Preexisting opioid (tramadol excluded), ketamine or midazolam therapy
    • General physical condition ≥ ASA IV
    • Serious intranasal or epipharyngeal problems
    • Mental / psychiatric disorder
    • Pregnancy
    • Patients with renal failure (clearance < 30 ml/min)
    • Patients with liver failure (MELD score > 25) Investigational Product Morphine / S-ketamine / midazolam
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01275547

Locations
Switzerland
University Hospital, Basel, Switzerland
Basel, Basel Stadt, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Wilhelm Ruppen, MD University Hospital, Basel, Switzerland
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01275547     History of Changes
Other Study ID Numbers: EKBB28/10
Study First Received: January 11, 2011
Last Updated: January 28, 2013
Health Authority: Switzerland: Ethikkommission

Keywords provided by University Hospital, Basel, Switzerland:
Patient controlled analgesia
Morphine
S-Ketamine intranasal
Midazolam intranasal

Additional relevant MeSH terms:
Spinal Stenosis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Analgesics
Ketamine
Morphine
Midazolam
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on August 01, 2014