Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03995134 |
| Other study ID # |
Pro00083505 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 3, 2019 |
| Est. completion date |
January 17, 2020 |
Study information
| Verified date |
January 2020 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this university study is to evaluate the use of an advanced dental sedation
technique involving two syringe-type pumps called Target Controlled Infusion (TCI) pumps. Two
oral surgeons and a general dentist from New Zealand are assisting a Canadian research team
as they study this intravenous sedation technique and its use in dental offices. This
sedation technique is broadly used in other parts of the world and is known to reduce anxiety
and discomfort during dental or medical procedures.
The New Zealand Dental Council and Health Canada have approved the drugs involved and the TCI
pumps. In this study, one pump will be used to administer a sedative drug called propofol and
the other to administer a pain-relief analgesic drug called remifentanil. The pumps and drugs
are licensed in New Zealand and Canada and are not experimental.
These pumps are operated by special software modules that are specific to each drug, and a
computer within the pump controls the pump operation allowing a stable and constant level of
drug in the blood stream.
Your oral surgeon or dentist will titrate or add small amounts of drug till the you are quite
relaxed before proceeding with your dental treatment. The dentist has overall control of the
pump and the amount of drug given and can change the amount if it is too little or too much
for you, or completely stop the pump if necessary for safety..
The TCI sedation, including your dental treatment will be conducted by two oral surgeons and
a general dentist in their respective New Zealand dental offices. Each clinician is well
trained and experienced with this form of sedation.
Description:
Purpose:
Moderate (conscious) sedation is a common pharmacological approach to managing psychological
anxiety and physical pain associated with dental procedures including surgery. While
maintaining patient responsiveness to verbal and tactile stimuli, safety of conducting
moderate sedation in dental clinic is well documented with infrequent complications.
Preferred drug choices for administering moderate intravenous (i.v.) sedation are midazolam
(benzodiazepine sedative) and fentanyl (opioid analgesic) because their safety and efficacy
have been well established and are currently considered the Standard of Care (SoC) worldwide.
The use of drugs intended for general anesthesia to provide moderate (conscious) sedation is
increasingly being considered for dental sedation as there are a number of benefits when
compared to the SoC. For example, propofol has a favorable pharmacokinetic profile and
absence of lingering side-effects; drugs (propofol and remifentanil) with fast onset and
offset times are most useful for balancing adequate hypnosis/analgesia with rapid recovery.
This clinical research study will explore the potential benefits of controlled administration
of propofol (hypnotic agent) and remifentanil (opioid analgesic agent) utilizing two Target
Controlled Infusion (TCI) pumps for moderate i.v. sedation by a sedationist/operator in a
dental office-based environment.
Standardized care for moderate (conscious) sedation is guided by the following principle:
Drugs and techniques used to provide moderate (conscious) sedation for dental treatment
should carry a margin of safety wide enough to render loss of consciousness unlikely.
The level of sedation must be such that the patient remains conscious and is able to both
understand and respond to verbal commands either alone or accompanied by light tactile
stimulus; Modified Ramsay Sedation score of 3 or 4 .
The current SoC for i.v. dental sedation in Canada and New Zealand is the administration of a
single benzodiazepine agent alone or in combination with an opioid analgesic agent to achieve
moderate or conscious sedation whereby the patient responds to voice or light tough stimulus
throughout the procedure.
The purpose of this study is to explore the advantages/disadvantages and risks/benefits of
TCI interventional sedation technique in an dental office-based environment.
Hypothesis:
Increasingly, the controlled use of propofol and remifentanil utilizing pharmacokinetic
programmed syringe pumps called Target Controlled Infusion (TCI) pump are being considered as
an alternative option for dental sedation for the operator/sedationist and their sedation
team. Is this sedation technique a viable option to the SoC?
Within the TCI system, specific pharmacokinetic algorithms have been developed for each drug,
accounting for drug distribution, elimination, and metabolism, thus providing a stable,
constant concentration of drug at the plasma (blood) or brain level. The drugs used are short
acting, thus the clinician can quickly titrate the drugs to the desired sedative effect and
if necessary can incrementally increase or decrease the drug's sedative/analgesic effect to
meet patient's needs and procedural stimulus. In sum, the short-acting nature of the drugs,
combined with a specified delivery algorithm have the potential in allowing better patient
care in dental office setting through adapting dosage to patient needs, thus allowing better
control, a shorter recovery time with early home readiness.
Justification:
Adequacy of procedural sedation depends on the maintenance of brain propofol and remifentanil
concentrations which are clinically appropriate and in equilibrium with levels in the plasma.
The best way to achieve this state is from TCI dedicated pharmacokinetic pumps. These devices
solve the complex equations which describe the distribution of agents between compartments
and allow for rapid adjustments in targets to achieve the desired clinical effect.
Health Canada has approved the use of propofol and remifentanil for on-label use for dental
sedation and anesthesia, and has approved the Alaris PK infusion pump with TCI for use in
Canada. New Zealand Dental Council has also approved and permitted propofol and remifentanil
and the Alaris PK infusion pump for dental sedation.
American Society of Anesthesiologist's Moderate Sedation Guidelines 2018 provides guidance
and recommendations that include sedative/analgesic medications intended for general
anesthesia (propofol and remifentanil) can also be safely administered for moderate sedation
across health professions and environments.
A published research study exploring the use of TCI pump technology in medicine to the year
2015, conservatively estimated the following:
- Use worldwide >90 countries.
- TCI pump sales >60,000 units.
- Anesthesia and sedation >20 million administrations.
- Commercial usage of TCI process >2 decades in clinical use.
Dr. Lobb is unaware of:
- Any dentist/dental specialist in Canada using propofol and remifentanil with TCI
technology for moderate sedation.
- Any dental college in Canada that has issued a permit to use propofol and remifentanil
with TCI technology for moderate sedation.
- Any Canadian university involved in clinical research using propofol and remifentanil
with TCI technology for dental sedation.
Thus, to advance important and relevant Canadian clinical research in the administration of
propofol and remifentanil with TCI pumps for sedation dentistry, Dr. Lobb has invited dental
experts outside of Canada to partner with a research team from the University of Alberta. The
following reasons justifies this rationale:
Oral surgeons in New Zealand have been world leaders in the use of TCI sedation in dentistry
for over a decade. The two pump TCI sedation process has become a Standard of Care in a
number of dentist/dental specialist offices.
The New Zealand dental group licensed to administer propofol and remifentanil with TCI pump
technology includes oral surgeons, oral and maxillofacial surgeons and general dentists,
with:
- >10 years' experience with TCI sedation.
- >40,000 collective administrations.
- Two New Zealand oral surgeons and a general dentist have consented to participate in
this clinical research study. All three are experienced TCI sedation practitioners.
- The clinical phase of this research study will be completed within their respective
dental practice facilities in New Zealand.
- he population numbers and demographic profile of New Zealand is quite similar to
Alberta.
- The type of dental surgery and general dentistry performed in New Zealand is similar in
scope to that practiced by Alberta dental practitioners.
Objectives:
The overall objective of the research is to validate a sedation technique that is proposed to
be more controllable and less intrusive to patients. Specifically, in this prospective pilot
study, we seek to determine the safety, effectiveness, and comparability of the controlled
administration of propofol and remifentanil utilizing two TCI syringe pumps for moderate
sedation in dentistry through establishing, identifying, and refining a study protocol in
this pilot study in preparation for a larger study, or a replication study in Canada.
Research Methods/Procedures:
This is a prospective, pilot study, with the TCI sedation and clinical component of the study
being completed by two oral surgeons and one general dentist in New Zealand. The rationale
for having the sedation and clinical treatment performed in New Zealand is there are no
dentists/dental specialists licensed by the Alberta Dental Association and College to use
this form of i.v. sedation in Alberta at this time.
All treatment will occur at the oral surgery offices of Drs. Don Macalister and David Chrisp
in Auckland and Taruanga respectively, and general dental office of Dr. Graham Shaw in
Auckland, New Zealand.
A total of 100 patients are the requirement for this pilot study across three sites. This
study will be of nine months' duration, from September 1, 2018 to June 30, 2019, or when 40
patients have been successfully recruited to the study at each site oral surgery site and 20
at the general dentistry site.
Intravenous sedation study participants will receive the established TCI dental i.v. sedation
consistent to each oral surgeon and general dentist office protocol.
The participating oral surgeons/dentist will abide by any research protocols established by
the New Zealand Ethics Office, and the University of Alberta, Research Ethics Office.
During the sedation: the use of appropriate physiologic and electronic monitoring,
standardized intravenous administration sets, TCI infusion pumps, personnel, record keeping
and discharge criteria will be used. Brain function monitoring (pEEG) provides additional
information to the clinician during titration of propofol and remifentanil.
Post-sedation, all patients are followed up with a phone call and if there are any concerns,
the patients will be seen immediately. In the event of any problems or concerns after hours,
the phone number of the oral surgeon/dentist is available on the post-sedation instruction
sheet.
Immediately following the sedation and prior to discharge, the participants will be asked a
series of questions from the patient satisfaction questionnaire. In the follow-up portion of
the study, participants will be asked the same series of questions from the patient
satisfaction questionnaire; 24 - 48 hours following the sedation.
TCI sedation involves the use of controlled administration of propofol and remifentanil
utilizing two TCI pumps (Alaris PK infusion pump with TCI). The software models used in New
Zealand differ slightly from that currently available in Canada. In New Zealand effect-site
or brain level software (Schnider for propofol and Minto for remifentanil) will be used.
In Canada, the licensed software for the same pump is plasma level software (Marsh for
propofol and Minto for remifentanil).
The propofol TCI models (Schnider or Marsh) prove highly effective in combination with
remifentanil TCI. Clinical practice demonstrates there is no 'best' TCI model for propofol.
The clinician should become familiar with the model which matches the patient characteristics
of their usual patient population. Regardless of pharmacokinetic model used, clinical
monitoring of the patient remains an important and integral part of the sedation team's role
and patient care.
The dental procedures will be what is normally performed in each New Zealand office, and the
scope of these procedures is similar to that performed by dental practitioners in Alberta.
Plan for Data Analysis:
Independent t-test and analysis of covariance will be used to compare differences in safety
and effectiveness measures as described. Box M test will be used to evaluate comparability of
variance between sites. A statistical covariate will also be used to conduct comparison of
results taking account of the risk associated with patient demographics.
Data collected from patients will first be processed such that values across multiple
time-points, collected through survey and patient record, will reflect as one record.
Incomplete or problematic records will be removed from the analysis. Descriptive statistics
will be presented for all measures of secondary objectives, confidence interval estimates,
proportion and statistical tests will be conducted to evaluate safety and effectiveness
findings.
