Trial Outcomes & Findings for Healozone Study to Evaluate the Safety and Efficacy of the Use of Ozone for Management of Dental Caries (NCT NCT00495495)

Results Overview

Clinically significant changes indicating caries progression are defined as changes in ICDAS severity values from 1 or 2 to a 3 or higher, or from a 3 or 4 to a 5 or higher. The severity criteria are as follows: 0 = Sound tooth surface. 1. = First visual change in enamel. 2. = Distinct visual change in enamel. 3. = Localized enamel breakdown due to caries with no visible dentin. 4. = Underlying dark shadow from dentin, with or without localized enamel breakdown. 5. = Distinct cavity with visible dentin. 6. = Extensive distinct cavity with visible dentin.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

394 participants

Primary outcome timeframe

Baseline and One Year

Results posted on

2015-02-20

Participant Flow

Participant milestones

Participant milestones
Measure	Ozone Treatment and Placebo Treatment 60-second Ozone device treatment compared to 60-second Placebo device treatment. Study utilized split-mouth design. The paired treatment assignment for the two teeth within each subject was performed according to a randomization table provided by the Biometrician. Randomization of teeth to Ozone treatment or Placebo treatment was stratifed according to tooth similarity.
Overall Study STARTED	394
Overall Study COMPLETED	295
Overall Study NOT COMPLETED	99

Reasons for withdrawal

Reasons for withdrawal
Measure	Ozone Treatment and Placebo Treatment 60-second Ozone device treatment compared to 60-second Placebo device treatment. Study utilized split-mouth design. The paired treatment assignment for the two teeth within each subject was performed according to a randomization table provided by the Biometrician. Randomization of teeth to Ozone treatment or Placebo treatment was stratifed according to tooth similarity.
Overall Study Protocol Violation	99

Baseline Characteristics

Healozone Study to Evaluate the Safety and Efficacy of the Use of Ozone for Management of Dental Caries

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ozone Treatment/Placebo Treatment n=394 Participants Study utilized split-mouth design. Each participant had two teeth selected at the start of the study. Each participant was then randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds and Placebo treatment on a randomly selected study tooth for 60 seconds.
Age, Categorical <=18 years	102 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	292 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	22.9 years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	202 Participants n=5 Participants
Sex: Female, Male Male	192 Participants n=5 Participants
Region of Enrollment United States	394 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and One Year

Population: The study utilized a split-mouth design. The results posted are for the Per Protocol dataset. Subjects who completed all four treatment/examination visits as well as final examination visit without major protocol violations were included in this dataset.

Clinically significant changes indicating caries progression are defined as changes in ICDAS severity values from 1 or 2 to a 3 or higher, or from a 3 or 4 to a 5 or higher. The severity criteria are as follows: 0 = Sound tooth surface. 1. = First visual change in enamel. 2. = Distinct visual change in enamel. 3. = Localized enamel breakdown due to caries with no visible dentin. 4. = Underlying dark shadow from dentin, with or without localized enamel breakdown. 5. = Distinct cavity with visible dentin. 6. = Extensive distinct cavity with visible dentin.

Outcome measures

Outcome measures
Measure	Ozone Treatment n=295 teeth As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.	Placebo Treatment n=295 teeth As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
ICDAS Severity Value Number of Teeth with Caries Progression	17 teeth	22 teeth
ICDAS Severity Value Number of Teeth with No Caries Progression	278 teeth	273 teeth

SECONDARY outcome

Timeframe: Baseline and one year

Population: Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations. Clinically significant changes for Activity Scores were indicated by a change in caries activity status from active to inactive. It should be noted that all teeth were considered active at baseline.

Change in caries lesion activity at One Year. All teeth were considered Active at Baseline Caries Lesion Activity score: 1. = Inactive - surface of enamel appears whitish, brownish or black. Enamel may be shiny and feels hard and smooth when the tip of the probe is moved gently across the surface. 2. = Active lesion - surface of enamel appears whitish/yellowish opaque with loss of luster. The surface feels rough when the tip of the probe is moved gently across the surface.

Outcome measures

Outcome measures
Measure	Ozone Treatment n=295 teeth As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.	Placebo Treatment n=295 teeth As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Change in Caries Lesion Activity Number of Active Caries lesions	189 teeth	164 teeth
Change in Caries Lesion Activity Number of Non- Active Caries Lesions	106 teeth	131 teeth

SECONDARY outcome

Timeframe: one year

Population: Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations (subjects who completed all four treatment/examination visit at Baseline, 3-, 6-, 9-month as well as Final examination at 12-month.

Clinically significant changes for Bitewing x-rays indicating caries progression would be changes in x-ray criterion for lesion presence from "no" to "yes" or for lesion depth to a D1 or higher. The occlusal surface of study teeth will be evaluated using the following scale: Lesion presence: yes /no Lesion depth: E1 = outer half of enamel E2 = inner half of enamel D1 = outer third of dentin D2 = middle third of dentin D3 = inner third of dentin or greater/pulpal exposure

Outcome measures

Outcome measures
Measure	Ozone Treatment n=295 teeth As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.	Placebo Treatment n=295 teeth As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Progression of Radiographic Scores at 12 Months Number of Teeth with Progression	6 teeth	12 teeth
Progression of Radiographic Scores at 12 Months Number of Teeth with No Progression	220 teeth	214 teeth

SECONDARY outcome

Timeframe: one year

Population: Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations (subjects who completed all four treatment/examination visit at Baseline, 3-, 6-, 9-month as well as Final examination at 12-month.

The change in DIAGNOdent measurements between baseline and twelve-month visits was used as an additional secondary endpoint. Clinically significant changes for DIAGNOdent indicating caries progression would be an increase in DIAGNOdent reading of 10 or more units or an increase in DIAGNOdent reading from below 20 to above 30 units. DIAGNOdent reading using a scale from 00 to 99, with 00 indicating no caries activity and 99 indicating a high level of activity.

Outcome measures

Outcome measures
Measure	Ozone Treatment n=293 teeth As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.	Placebo Treatment n=293 teeth As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Laser Fluorescence Progression-12 Month (Increase From <=20 to >=30) Number of Teeth with Progression	16 teeth	14 teeth
Laser Fluorescence Progression-12 Month (Increase From <=20 to >=30) Number of Teeth with No Progression	277 teeth	279 teeth

SECONDARY outcome

Timeframe: one year

Population: Analyses were based on per protocol subjects, defined as all randomized subjects with no major protocol violations.

The change in DIAGNOdent measurements between baseline and twelve-month visits was used as an additional secondary endpoint. Clinically significant changes for DIAGNOdent indicating caries progression would be an increase in DIAGNOdent reading of 10 or more units. DIAGNOdent reading using a scale from 00 to 99, with 00 indicating no caries activity and 99 indicating a high level of activity.

Outcome measures

Outcome measures
Measure	Ozone Treatment n=293 teeth As part of the split-mouth design, subjects were randomized to receive Ozone treatment on a randomly selected study tooth for 60 seconds.	Placebo Treatment n=293 teeth As part of the split-mouth design, subjects were randomized to receive placebo treatment on a randomly selected study tooth for 60 seconds.
Laser Fluorescence Progression-12 Month (Increase at Least 10) Number of Teeth with Progression	58 teeth	52 teeth
Laser Fluorescence Progression-12 Month (Increase at Least 10) Number of Teeth with No Progression	235 teeth	241 teeth

Adverse Events

Ozone Treatment and Placebo Treatment

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ozone Treatment and Placebo Treatment n=394 participants at risk Study utilized split-mouth design. Each participant had two teeth selected at the start of the study. Each participant was then randominzed to receive Ozone treatment on a randomly selected study tooth for 60 seconds and Placebo treatment on a randomly selected study tooth for 60 seconds.
General disorders Appendicitis	0.25% 1/394 • Number of events 1 • The adverse events were collected during the one-year period of the trial.
Reproductive system and breast disorders Surgery ovarian cyst removal	0.25% 1/394 • Number of events 1 • The adverse events were collected during the one-year period of the trial.
Reproductive system and breast disorders surgery breast reduction	0.25% 1/394 • Number of events 1 • The adverse events were collected during the one-year period of the trial.
Musculoskeletal and connective tissue disorders Broken left leg	0.25% 1/394 • Number of events 1 • The adverse events were collected during the one-year period of the trial.
Musculoskeletal and connective tissue disorders Broken left knee	0.25% 1/394 • Number of events 1 • The adverse events were collected during the one-year period of the trial.

Other adverse events

Adverse event data not reported

Additional Information

Domenick T. Zero, DDS MS Principal Investigator

Indiana University School of Dentistry

Phone: 317-274-8822

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place