Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01275547
Recruitment Status : Completed
First Posted : January 12, 2011
Last Update Posted : January 29, 2013
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE January 11, 2011
First Posted Date  ICMJE January 12, 2011
Last Update Posted Date January 29, 2013
Study Start Date  ICMJE January 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2011)
Numeric rating scale 24 hours after surgery [ Time Frame: 24 hours ]
NRS after 24 hours after finishing surgery
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2011)
Amount of PCA boli [ Time Frame: 72 hours ]
Amount of demanded / delivered unit doses of intranasal S-ketamine / midazolam or morphine PCA-boli
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam
Official Title  ICMJE The Analgesic Effect of Combined Treatment With Intranasal S-Ketamine and Intranasal Midazolam Compared With Morphine Patient Controlled Analgesia in Spinal Surgery Patients
Brief Summary

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A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m..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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE
  • Analgesia, Patient-controlled
  • Spinal Stenosis
Intervention  ICMJE
  • Drug: s-ketamine & midazolam
    s-ketamine 6 mg intranasal midazolam 0.75 mg intranasal
  • Drug: Morphine PCA
    2 mg Morphine i.v. all 12 minutes as a patient controlled system
Study Arms  ICMJE
  • Experimental: S-ketamine & midazolam spray
    all 20 minutes as a patient controlled analgesia alternating s-ketamine / midazolam
    Intervention: Drug: s-ketamine & midazolam
  • Active Comparator: morphine, patient controlled analgesia
    morphine as an active comparator as a patient controlled analgesia system
    Intervention: Drug: Morphine PCA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 28, 2013)
22
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2011)
36
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01275547
Other Study ID Numbers  ICMJE EKBB28/10
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wilhelm Ruppen, MD University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP