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

Phase 2

Completed

• Conditions: Analgesia, Patient-controlled; Spinal Stenosis
• Interventions: Drug: s-ketamine & midazolam; Drug: Morphine PCA

• Registration Number: NCT01275547
• Lead Sponsor: University Hospital, Basel, Switzerland

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A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m..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

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-01-11
• Study First Submitted QC: 2011-01-11
• Study First Posted: 2011-01-12
• Primary Completion: 2011-06
• Study Completion: 2011-12
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-28
• Last Update Posted: 2013-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
S-ketamine & midazolam spray	s-ketamine & midazolam	all 20 minutes as a patient controlled analgesia alternating s-ketamine / midazolam
morphine, patient controlled analgesia	Morphine PCA	morphine as an active comparator as a patient controlled analgesia system

Primary Outcome Measures

Name	Time	Method
Numeric rating scale 24 hours after surgery	24 hours	NRS after 24 hours after finishing surgery

Secondary Outcome Measures

Name	Time	Method
Amount of PCA boli	72 hours	Amount of demanded / delivered unit doses of intranasal S-ketamine; / midazolam or morphine PCA-boli

Trial Locations

Locations (1)

University Hospital, Basel, Switzerland; 🇨🇭 Basel, Basel Stadt, Switzerland