Remimazolam vs Midazolam Cognitive and Motor Recovery After Intravenous Conscious Sedation for Dental Extractions.

NCT ID: NCT05220462

Last Updated: 2023-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-09

Study Completion Date

2024-09-01

Brief Summary

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The study is looking to see if a new drug (remimazolam) that is used to sedate and relax adults (aged 18-59 years) having dental treatment is better than the current drug in use (midozolam). Intravenous sedation is where a drug is injected into a patient's hand or arm. The drug stops them feeling worried, and helps them relax. After sedation, patients wait in a recovery area until they are safe to walk but the side effects of the drug can last until the next day. A new drug has been developed that has the same sedation effect and safety, but the recovery is much quicker. The investigators think that the side effects from the new drug will have worn off by the time patients are ready to leave the hospital. Patients who are coming to Guy's Hospital to have their wisdom tooth extracted under sedation will be asked if they want to be included in the research. Patients will be randomised to receive either remimazolam of standard of care midazolam. The sedation and dental treatment will be carried out in the normal way.

The patients will be asked to do will be some questionnaires and some tests which are as follows:

1. Patients are asked to listen to some words and repeat them back. This tests how well they can remember new information
2. Reaction test - Patients are asked to rest their fingers on a keypad and move their fingers when lights come on above them. This tests how quick their reactions are.
3. Symbol test- Patients are asked to draw small shapes that are linked to numbers. This tests how well they can process information.
4. Standing test- Patients are asked to stand on a platform that measures how much they are swaying back and forth. This tests how stable they are to walk.

By testing people before and after the sedation the investigators can see how they recovered and compare the two drugs. The research will take place during the day case visit and involve 2 x 30 mins research assessments (before sedation and post sedation). After the post-sedation tests, participants will be discharged, followed by a telephone review 3-10 days post procedure.

Detailed Description

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This study will be performed as a prospective, randomised, triple blind, active controlled, parallel group, single centre study design assessing enhanced cognitive recovery in patients having third molar wisdom tooth extraction under intravenous conscious sedation with remimazolam. An active control group has been chosen using intravenous midazolam which is the current standard of care in Dentistry. 128 patients will be randomised, of which n=64 will receive remimazolam, and n=64 in the midazolam group.

Conditions

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Tooth Extraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Remimazolam

White to off-white lyophilised powder, presented in a 12 mL clear glass vial with a grey bromobutyl stopper, fitted with an aluminium crimp and a blue plastic flip-off cap. Each 20 mg vial of remimazolam, will be reconstituted with sterile 0.9% NaCl solution to yield a 2.5 mg/mL solution for injection.

An initial dose of 5mg (2mL) over 60 seconds, pausing for 90 seconds, followed by 2.5mg (1mL) over 30 seconds and waiting 30 seconds will be titrated to response end point. Subsequent doses of 2.5mg (1 mL) increments can be administered if required should the procedure take longer, or the patient recover more quickly than expected, to maintain the sedation level. Top-up doses will be administered slowly, at least 2 minutes apart. Top-up doses will be limited to a maximum of 5 doses in a 15-minute window. Additionally, a maximum dose of 40mg of remimazolam (16mL) will be set.

Group Type EXPERIMENTAL

Remimazolam

Intervention Type DRUG

As per Remimazolam arm

Midazolam

Midazolam will be presented as a solution in a 5 mL ampoule. Each ampoule will contain 5 mg of midazolam, yielding a 1 mg/mL solution for injection.

Dosing of midazolam was based on local formulary and standard of care / local guidance. An initial dose of 2mg (2mL) over 60 seconds, pausing for 90 seconds, followed by 1mg (1mL) over 30 seconds and waiting 30 seconds will be titrated to response end point. Subsequent doses of 1mg (1 mL) increments can be administered if required should the procedure take longer, or the patient recover more quickly than expected, to maintain the sedation level. Top-up doses will be administered slowly at least 2 minutes apart. Top-up doses will be limited to a maximum of 5 doses in a 15-minute window. Additionally, a maximum of dose of 16mg of midazolam (16mL) will be set.

Group Type ACTIVE_COMPARATOR

Midazolam

Intervention Type DRUG

As per Midazolam arm

Interventions

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Remimazolam

As per Remimazolam arm

Intervention Type DRUG

Midazolam

As per Midazolam arm

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients who are scheduled to have mandibular third molar removal with intravenous conscious sedation.
* Male and female patients, aged ≥18 to ≤59 years old.
* American Society of Anesthesiologists (ASA-PS) grade I or II.
* English as their first or main language for 5+ years. The primary outcome measure (HVLT) is a cognitive test to remember English words and validated on this basis.
* A patient who has given informed written consent for inclusion to the study.
* Patients who are willing and able to comply with study requirements.

Exclusion Criteria

* Any surgical risk factor which, in the opinion of the study surgeon, can lead to increased procedure complexity (for example high risk of inferior alveolar nerve damage)
* A known sensitivity to benzodiazepines or a medical condition such that these agents are contraindicated as per the SmPC, for example unstable myasthenia gravis, hepatic impairment, acute respiratory depression, and severe respiratory failure.
* Any neurological deficit where cognitive tests will be impaired (for example dementia).
* A patient with known difficult airway/ mask ventilation or who has increased risk factors recorded by the clinical team at assessment.
* A patient who reports hypersensitive gag reflex.
* Body mass index \>34.9 kg/m or weight \<50kg or \>130kg.
* Dental or needle phobia identified by a modified dental anxiety score ≥19 (MDAS questionnaire).
* High Hospital Anxiety and Depression Score (HADS) \>12.
* Chronic use of benzodiazepines or opioids for any indication.
* Use of medications known to interact with IMP or comparator as listed in the SmPC.
* All female patients with a positive urine pregnancy test within 8 hours before IMP administration. Female patients who are permanently sterile are not required to have a urine test. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
* Lactating female patients currently breastfeeding.
* Patients who self-report illicit drug use in the last 4 weeks. Patients who self-report alcohol abuse (AUDIT-C Scores \> 7) or history of abuse within the past 5 years.
* Patients who self-report a history of illicit drug abuse within the past 5 years or any history of benzodiazepine dependence.
* Inclusion in a study of an IMP in the previous 4 weeks or less than seven half-lives (whichever is the longer).
* Hypersensitivity to the IMP or to any of the excipients.
* Patients who are unable to stand unassisted.
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bryan Kerr

Role: PRINCIPAL_INVESTIGATOR

Guy's and St Thomas' NHS Foundation Trust

Locations

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Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Bryan Kerr

Role: CONTACT

Phone: 02071887188

Email: [email protected]

Facility Contacts

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Bryan Kerr

Role: primary

Other Identifiers

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1003587

Identifier Type: -

Identifier Source: org_study_id