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

NCT01275547 | Completed Phase 2

• 1 other identifier: EKBB28/10
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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 A new formulation of S-ketamine as an intranasal spray device was tested in our hospital in 8 healthy volunteers (unpublished data, EKBB 351/08). 20 mg of S-ketamine were administered intranasally and compared with S-ketamine i.v. and i.m..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

Conditions

Analgesia, Patient-controlled; Spinal Stenosis

Keywords

Patient controlled analgesia; Morphine; S-Ketamine intranasal; Midazolam intranasal

Outcome Measures

Primary Outcomes (1)

• Numeric rating scale 24 hours after surgery

  NRS after 24 hours after finishing surgery

  24 hours

Secondary Outcomes (1)

• Amount of PCA boli

  72 hours

Study Arms (2)

S-ketamine & midazolam spray

EXPERIMENTAL

all 20 minutes as a patient controlled analgesia alternating s-ketamine / midazolam

Drug: s-ketamine & midazolam

morphine, patient controlled analgesia

ACTIVE COMPARATOR

morphine as an active comparator as a patient controlled analgesia system

Drug: Morphine PCA

Interventions

s-ketamine & midazolam DRUG

s-ketamine 6 mg intranasal midazolam 0.75 mg intranasal

S-ketamine & midazolam spray

Morphine PCA DRUG

2 mg Morphine i.v. all 12 minutes as a patient controlled system

morphine, patient controlled analgesia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Spinal surgery patients with:
• decompression because of spinal stenosis
• laminectomy because of spinal stenosis
• Age \> 18 years
• BMI 18 - 39.9 (kg/m2)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital, Basel, Switzerland

Basel, Canton of Basel-City, 4031, Switzerland

Location

MeSH Terms

Conditions

Agnosia; Spinal Stenosis

Interventions

Esketamine; Midazolam

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Wilhelm Ruppen, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2011
• First Posted: January 12, 2011
• Study Start: January 1, 2011
• Primary Completion: June 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 29, 2013

Record last verified: 2013-01

Locations

CH (1)