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

January 11, 2011
January 28, 2013
January 2011
June 2011   (final data collection date for primary outcome measure)
Numeric rating scale 24 hours after surgery [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
NRS after 24 hours after finishing surgery
Same as current
Complete list of historical versions of study NCT01275547 on ClinicalTrials.gov Archive Site
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

Same as current
Not Provided
Not Provided
 
The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam
The Analgesic Effect of Combined Treatment With Intranasal S-Ketamine and Intranasal Midazolam Compared With Morphine Patient Controlled Analgesia in Spinal Surgery Patients

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A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m..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

Not Provided
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
  • Analgesia, Patient-controlled
  • Spinal Stenosis
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
December 2011
June 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
NCT01275547
EKBB28/10
No
University Hospital, Basel, Switzerland
University Hospital, Basel, Switzerland
Not Provided
Principal Investigator: Wilhelm Ruppen, MD University Hospital, Basel, Switzerland
University Hospital, Basel, Switzerland
January 2013

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