- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01275547
The Analgesic Effect of Combined Treatment With Intranasal S-ketamine and Intranasal Midazolam (NASKEMI)
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A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m..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:
- 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
- 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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
Basel Stadt
-
Basel, Basel Stadt, Switzerland, 4031
- University Hospital, Basel, Switzerland
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: S-ketamine & midazolam spray
all 20 minutes as a patient controlled analgesia alternating 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
|
2 mg Morphine i.v.
all 12 minutes as a patient controlled system
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Numeric rating scale 24 hours after surgery
Time Frame: 24 hours
|
NRS after 24 hours after finishing surgery
|
24 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Amount of PCA boli
Time Frame: 72 hours
|
Amount of demanded / delivered unit doses of intranasal S-ketamine / midazolam or morphine PCA-boli |
72 hours
|
Collaborators and Investigators
Investigators
- Principal Investigator: Wilhelm Ruppen, MD, University Hospital, Basel, Switzerland
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Musculoskeletal Diseases
- Spinal Diseases
- Bone Diseases
- Spinal Stenosis
- 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
- Analgesics, Opioid
- Narcotics
- Tranquilizing Agents
- Psychotropic Drugs
- Antidepressive Agents
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Ketamine
- Midazolam
- Morphine
- Esketamine
Other Study ID Numbers
- EKBB28/10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Spinal Stenosis
-
RTI SurgicalCompletedSpinal Disease | Spinal Instability | Spinal Stenosis Occipito-Atlanto-Axial | Spinal Stenosis Cervical | Spinal Stenosis Cervicothoracic RegionUnited States
-
Sutherland Medical CenterActive, not recruitingSpinal Stenosis Lumbar | Spinal Canal StenosisPoland
-
Massachusetts General HospitalCompletedLumbar Spinal Stenosis | Thoracic Spinal StenosisUnited States
-
Azienda Usl di BolognaRecruitingLumbar Spinal Stenosis | Degenerative Lumbar Spinal StenosisItaly
-
University Hospital, Basel, SwitzerlandKlinik für Radiologie und Nuklearmedizin, University Hospital BaselCompletedLumbar Spinal Stenosis | Symptomatic Lumbar Spinal StenosisSwitzerland
-
Sklifosovsky Institute of Emergency CarePirogov National Medical Surgical Center; Federal State Budgetary Institution... and other collaboratorsActive, not recruitingLumbar Spinal Stenosis | Spinal Stenosis | Spinal FusionRussian Federation
-
Region ZealandRegion SyddanmarkRecruiting
-
Tang-Du HospitalNot yet recruiting
-
Sisli Hamidiye Etfal Training and Research HospitalCompletedLumbar Spinal StenosisTurkey
Clinical Trials on s-ketamine & midazolam
-
Eye & ENT Hospital of Fudan UniversityCompletedPain, Procedural | Emotions | Separation AnxietyChina
-
Turku University HospitalUniversity of Turku; University of HelsinkiCompletedPain, PostoperativeFinland
-
Universidade Federal de GoiasConselho Nacional de Desenvolvimento Científico e TecnológicoCompletedDental Caries | Child BehaviorBrazil
-
Medical University of ViennaUnknownDepression | KetamineAustria
-
National University of MalaysiaRecruitingPancreatic Cancer | Cholangitis | Choledocholithiasis | Choledochal CystMalaysia
-
Universidade Federal de GoiasCompleted
-
Wake Forest University Health SciencesCompletedCataract | Phacoemulsification
-
Erasmus Medical CenterEnrolling by invitationComplex Regional Pain Syndromes | CRPS (Complex Regional Pain Syndromes)Netherlands
-
Medical University of ViennaRecruiting