Dental Prophylaxis and Implant Surgery
Conditions
Brief summary
The primary objective of this study will be to evaluate the effect of two week pre-surgical rinsing with an antimicrobial mouthrinse containing 0.2% w/v Chlorhexidine digluconate on the total number of plaque bacteria in the mouth 3 days post implant surgery. The study will be conducted at Eastman Clinical Investigation Centre (ECIC), University College London (UCL) Eastman Dental Institute. Participants will be those who require a single and simple surgical implant to be placed, and will be recruited from new patient referrals within the Eastman Dental Hospital
Interventions
DRUG0.2% w/v Chlorhexidine digluconate
Participants will brush their teeth with the reference product (toothpaste) and thoroughly rinse their mouth with water and wait 5 timed minutes before using 10 ml of the 0.2% w/v Chlorhexidine digluconate mouthwash, except when using at site, where no brushing will take place prior to using the mouthrinse.
DRUGSodium fluoride toothpaste (Aquafresh Mild & Minty)
Participants will apply a strip of toothpaste to cover the head of the toothbrush and will brush in their usual manner for two timed minutes twice daily. They will then rinse their mouth thoroughly with water after brushing
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form. * Aged between 18-64 years old. * Understands and is willing, able and likely to comply with all study procedures and restrictions * Good general and mental health with, in the opinion of the investigator or medically qualified designee: 1. No clinically significant and relevant abnormalities in medical history or upon oral examination. 2. Absence of any condition that could affect the participant's safety or well being or their ability to understand and follow study procedures and requirements. * Females of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception * Dental Health 1. Good overall oral health in the opinion of investigator. 2. A minimum of 20 permanent teeth. 3. Requiring a single and simple implant (single tooth replacement with no bone augmentation required for implant placement). * Females of childbearing potential who are, in the opinion of the investigator, practising a reliable method of contraception.
Exclusion criteria
* Women who are known to be pregnant or who are intending to become pregnant over the duration of the study * Women who are breast-feeding * Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients * Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit * Previous participation in this study * Recent history (within the last 1 year) of alcohol or other substance abuse * Use of antibiotics within 14 days prior to the Baseline visit or Implant surgery visit. * An employee of the sponsor or the study site or members of their immediate family
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Detectable Plaque Bacteria Sampled 3 Days Post Implant Surgery | At Day 3 | The examiner identified three plaque sampling sites as follows: surgical site, contralateral site to the surgical site and tongue. An individual cotton swab was used at each identified site for up to 20 seconds in order to harvest a plaque sample and immediately be placed into 1mL phosphate buffered saline in a sterile Eppendorf tube. The samples were analysed using quantitative polymerase chain reaction (qPCR) which determined the total number of bacteria in a sample by quantifying the number of 16S ribosomal ribonucleic acid (rRNA) genes in the sample. The number of bacteria in each of the three identified plaque sampling sites (surgical site, contralateral site to the surgical site and tongue) for each participant were summed to calculate the total number of bacteria for each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (pre-rinse, pre, mid and post implant surgery), Day 1 and 7 | The examiner identified three plaque sampling sites as follows: surgical site, contralateral site to the surgical site and tongue. An individual cotton swab was used at each identified site for up to 20 seconds in order to harvest a plaque sample and immediately be placed into 1mL phosphate buffered saline in a sterile Eppendorf tube. The samples were analysed using quantitative polymerase chain reaction (qPCR) which determined the total number of bacteria in a sample by quantifying the number of 16S ribosomal ribonucleic acid (rRNA) genes in the sample. |
| Area Under the Curve (AUC) for the Total Number of Plaque Bacteria in the Mouth Post Implant Surgery | Up to 7 days post implant surgery | The examiner identified three plaque sampling sites as follows: surgical site, contralateral site to the surgical site and tongue. An individual cotton swab was used at each identified site for up to 20 seconds in order to harvest a plaque sample and immediately be placed into 1mL phosphate buffered saline in a sterile Eppendorf tube. The samples were analysed using quantitative polymerase chain reaction (qPCR) which determined the total number of bacteria in a sample by quantifying the number of 16S ribosomal ribonucleic acid (rRNA) genes in the sample. The AUC of the total count of detectable plaque bacteria was calculated using trapezoidal rule in the time range from immediately post implant surgery to 7 days post implant surgery |
| Total Number of Recoverable Viable Bacteria in the Aerosol Generated During Dental Prophylaxis | At Baseline | Thick settle blood agar plates (supplemented with 5% \[volume by volume v/v\]) defibrinated horse blood) were used to determine the bacterial load of the aerosol. Thirty (30) minutes prior to the participants had their procedure (dental prophylaxis), a total of 5 settle plates with lids removed were placed at set positions around the dental surgery. After 30 minutes, the settle plates lids were replaced. This was repeated during the dental prophylaxis procedure using 5 fresh settle plates. All plates were then sealed with parafilm and transported for incubation in an anaerobic chamber at 37°C for 3 days. The plates were inspected daily to access growth and after 3 days removed and stored at 4°C for subsequent colony enumeration and Colony Forming Unit/mL (CFU/mL) calculation |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited from the one center in the United kingdom.
Pre-assignment details
A total of 44 participants were screened, out of which 38 were randomized. 6 participants were not randomized: 2 participants did not met study criteria, 2 participants withdrew their consent, 1 participant due to protocol violation, and 1 participant due to other reason (not specified).
Participants by arm
| Arm | Count |
|---|---|
| Test and Reference Product Participants rinsed for one timed minute with 10 mL of Test product (Mouthwash containing Chlorhexidine digluconate). Participants also applied a strip of reference product (toothpaste containing sodium fluoride) to cover the head of the toothbrush and brushed in their usual manner for two timed minutes first and thoroughly rinsed their mouth with water and waited for 5 timed minutes before using the mouthwash (except when used on site where they did not brush prior to using mouthwash). | 19 |
| Reference Product Participants applied a strip of reference product (toothpaste containing sodium fluoride) to cover the head of the toothbrush and brushed in their usual manner for two timed minutes. They then rinsed their mouth thoroughly with water after brushing. | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other (Not specified) | 0 | 2 |
Baseline characteristics
| Characteristic | Reference Product | Total | Test and Reference Product |
|---|---|---|---|
| Age, Continuous | 28.4 Years STANDARD_DEVIATION 12.23 | 27.9 Years STANDARD_DEVIATION 10.5 | 27.5 Years STANDARD_DEVIATION 8.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 35 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 32 Participants | 18 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 19 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 19 | 18 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Total Number of Detectable Plaque Bacteria Sampled 3 Days Post Implant Surgery
The examiner identified three plaque sampling sites as follows: surgical site, contralateral site to the surgical site and tongue. An individual cotton swab was used at each identified site for up to 20 seconds in order to harvest a plaque sample and immediately be placed into 1mL phosphate buffered saline in a sterile Eppendorf tube. The samples were analysed using quantitative polymerase chain reaction (qPCR) which determined the total number of bacteria in a sample by quantifying the number of 16S ribosomal ribonucleic acid (rRNA) genes in the sample. The number of bacteria in each of the three identified plaque sampling sites (surgical site, contralateral site to the surgical site and tongue) for each participant were summed to calculate the total number of bacteria for each participant.
Time frame: At Day 3
Population: Intent to treat (ITT) population (N=38): defined as all the participants who were randomised, received the study treatment at least once and provided at least one post-baseline assessment of efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled 3 Days Post Implant Surgery | 7.63 log(10) colony forming equivalents (CFE) | Standard Deviation 0.501 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled 3 Days Post Implant Surgery | 7.43 log(10) colony forming equivalents (CFE) | Standard Deviation 0.598 |
p-value: 0.296595% CI: [-0.18, 0.58]ANCOVA
Secondary
Area Under the Curve (AUC) for the Total Number of Plaque Bacteria in the Mouth Post Implant Surgery
The examiner identified three plaque sampling sites as follows: surgical site, contralateral site to the surgical site and tongue. An individual cotton swab was used at each identified site for up to 20 seconds in order to harvest a plaque sample and immediately be placed into 1mL phosphate buffered saline in a sterile Eppendorf tube. The samples were analysed using quantitative polymerase chain reaction (qPCR) which determined the total number of bacteria in a sample by quantifying the number of 16S ribosomal ribonucleic acid (rRNA) genes in the sample. The AUC of the total count of detectable plaque bacteria was calculated using trapezoidal rule in the time range from immediately post implant surgery to 7 days post implant surgery
Time frame: Up to 7 days post implant surgery
Population: ITT (N=38) defined as all the participants who were randomised, received the study treatment at least once and provided at least one post-baseline assessment of efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test and Reference Product | Area Under the Curve (AUC) for the Total Number of Plaque Bacteria in the Mouth Post Implant Surgery | 8.57 log (10) CFE × Day | Standard Deviation 0.319 |
| Reference Product | Area Under the Curve (AUC) for the Total Number of Plaque Bacteria in the Mouth Post Implant Surgery | 8.37 log (10) CFE × Day | Standard Deviation 0.356 |
Secondary
Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7)
The examiner identified three plaque sampling sites as follows: surgical site, contralateral site to the surgical site and tongue. An individual cotton swab was used at each identified site for up to 20 seconds in order to harvest a plaque sample and immediately be placed into 1mL phosphate buffered saline in a sterile Eppendorf tube. The samples were analysed using quantitative polymerase chain reaction (qPCR) which determined the total number of bacteria in a sample by quantifying the number of 16S ribosomal ribonucleic acid (rRNA) genes in the sample.
Time frame: At Day 0 (pre-rinse, pre, mid and post implant surgery), Day 1 and 7
Population: ITT (N=38) defined as all the participants who were randomised, received the study treatment at least once and provided at least one post-baseline assessment of efficacy. n was number of participants evaluated at specific endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (pre rinse), (n=19,19) | 7.55 log (10) CFE | Standard Deviation 0.376 |
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (pre implant), (n=19, 18) | 7.65 log (10) CFE | Standard Deviation 0.375 |
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (mid implant), (n=19, 18) | 7.58 log (10) CFE | Standard Deviation 0.449 |
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (post implant), (n=19,18) | 7.58 log (10) CFE | Standard Deviation 0.429 |
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 1 (n=19, 17) | 7.44 log (10) CFE | Standard Deviation 0.409 |
| Test and Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 7 (n=19, 17) | 7.72 log (10) CFE | Standard Deviation 0.335 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 1 (n=19, 17) | 7.06 log (10) CFE | Standard Deviation 0.47 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (pre rinse), (n=19,19) | 7.74 log (10) CFE | Standard Deviation 0.364 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (post implant), (n=19,18) | 7.81 log (10) CFE | Standard Deviation 0.433 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (pre implant), (n=19, 18) | 8.01 log (10) CFE | Standard Deviation 0.381 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 7 (n=19, 17) | 7.38 log (10) CFE | Standard Deviation 0.512 |
| Reference Product | Total Number of Detectable Plaque Bacteria Sampled at Implant Surgery (at Pre-rinse, Pre, Mid and Post Implant Surgery) and Post Implant Surgery (at Day 1 and 7) | At Day 0 (mid implant), (n=19, 18) | 7.84 log (10) CFE | Standard Deviation 0.597 |
Secondary
Total Number of Recoverable Viable Bacteria in the Aerosol Generated During Dental Prophylaxis
Thick settle blood agar plates (supplemented with 5% \[volume by volume v/v\]) defibrinated horse blood) were used to determine the bacterial load of the aerosol. Thirty (30) minutes prior to the participants had their procedure (dental prophylaxis), a total of 5 settle plates with lids removed were placed at set positions around the dental surgery. After 30 minutes, the settle plates lids were replaced. This was repeated during the dental prophylaxis procedure using 5 fresh settle plates. All plates were then sealed with parafilm and transported for incubation in an anaerobic chamber at 37°C for 3 days. The plates were inspected daily to access growth and after 3 days removed and stored at 4°C for subsequent colony enumeration and Colony Forming Unit/mL (CFU/mL) calculation
Time frame: At Baseline
Population: ITT (N=38) defined as all the participants who were randomised, received the study treatment at least once and provided at least one post-baseline assessment of efficacy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Test and Reference Product | Total Number of Recoverable Viable Bacteria in the Aerosol Generated During Dental Prophylaxis | Pre prophylaxis | 0.94 log (10) CFU/mL | Standard Deviation 0.435 |
| Test and Reference Product | Total Number of Recoverable Viable Bacteria in the Aerosol Generated During Dental Prophylaxis | Post prophylaxis | 1.31 log (10) CFU/mL | Standard Deviation 0.201 |
| Reference Product | Total Number of Recoverable Viable Bacteria in the Aerosol Generated During Dental Prophylaxis | Pre prophylaxis | 0.91 log (10) CFU/mL | Standard Deviation 0.606 |
| Reference Product | Total Number of Recoverable Viable Bacteria in the Aerosol Generated During Dental Prophylaxis | Post prophylaxis | 1.33 log (10) CFU/mL | Standard Deviation 0.326 |