Efficacy of Arnica Montana in Reducing Postoperative Edema and Pain Following Third Molar Extraction
Conditions: Arnica, Third Molar Extraction
Sponsor: Tufts University

 
 
 
 EFFICACY OF ARNICA 
MONTANA IN 
REDUCING 
POSTOPERATIVE 
EDEMA AND PAIN 
NCT03944629 
      
      
January 1, 2022 
      

Confidential 
 
 
 
Sample Size and Statistical Analysis 
 
Sample Size 
 
Assuming a mean volumetric change at Day 3 compared to baseline of 3.56 for 
placebo grou,24 and a mean volumetric change of 1.0 for arnica group (expected 
based on the PI’s clinical expertise), a standard deviation of 2.56, statistical 
significance level of .05, and two-sided test, 25 subjects per group (50 total) will be 
needed to achieve 93% power (nQuery Advisor 7.0). 
 
Up to thirty-five (35) subjects will be randomly assigned to each group. Recruitment 
will continue until up to seventy (70) subjects have qualified. This will allow for up 
to 29% dropout to end with a minimum of fifty (50) subjects completing the study. 
 
Statistical Analysis 
Descriptive statistics (mean and standard deviations for continuous variables, 
medians and IQR for ordinal variables, counts and percentages for categorical 
variables) will be calculated for each variable and stratified by the two treatment 
groups. 
 
For the primary outcome, the change in postoperative facial swelling as measured by 
the 3dMD™ system and the change in postoperative pain as measured by VAS, from 
baseline (pre-operative) to post-operative Day 3, and from baseline to post-operative 
Day 5, will be compared between the two groups using independent sample t-test if 
the data are normally distributed, or the Mann Whitney U test if non-parametric 
methods need to be utilized. 
 
In addition, the volume measurements and the VAS scores will be analyzed using a 
repeated measures ANOVA accounting for time effect, treatment effect, and 
treatment by time interaction, adjusting for subject age and sex. 
 
Number of rescue medication doses will be compared between the two treatment 
groups using Mann-Whitney U test. 
 
P-values less than 0.05 will be considered statistically significant. Statistical analyses 
will be performed using SAS, Version 9.4 (SAS Institute, Cary, North Carolina). 
 
3dMD™ 
 
An initial 3dMD™ scan will be obtained for a preoperative baseline evaluation at the 
extraction visit. A second 3dMD™ scan will be obtained for evaluation and 
determination of facial swelling at the Day 3 follow-up visit. A third scan will be 
obtained at the Day 5 follow-up visit to evaluate the degree of resolution of swelling. 
The scans will result in a computer-generated image on which the investigator will 
outline the area of clinical interest and calculate the volume using integration. The 

process of surface scanning and volume measurement will use the 3dMDvultus™ 
software. The 3dMDvultus™ software allows for superimposition of post-surgical 
images as well as quantitative evaluation of surface and volume changes. The 
Principal Investigator has worked on previous 3dMD™ studies and had additional 
training when the camera array was installed. The technique of obtaining the image 
is straight forward and there is a set of instructions at the installation site for 
immediate review as necessary. 
 
The degree of facial swelling between the two groups at the two time points (Day 3 
follow-up and Day 5 follow-up) will be compared using the data collected from 
3dMD™. Furthermore, the change in volume between the two scans taken at the Day 
3 follow-up visit and at the Day 5 follow-up visit within each group will also be 
compared. The volumetric difference between the two groups will be analyzed for any 
statistical significance. 
 
Randomization 
 
The subjects will be assigned to one of the two groups (arnica or placebo) at a ratio 
of 1:1 using a randomization scheme by the sponsor. Subjects will be randomized by 
a study coordinator. The master list/code corresponding to the study medication or 
placebo will be given to only the Principal Investigator, and only opened in the event 
that knowledge of the treatment the subject received is necessary. 
 
Blinding 
 
To decrease bias, this study will be double blinded by blinding information about the 
specific group from the subject and the investigators. The study medication and 
matching placebo (sugar pill) will be blinded and packaged in blister cards provided 
by the Sponsor. 
 
Only the Principal Investigator and the Research Coordinator will have access to the 
sealed chart numbers that identify the medication used, and the code will only be 
broken at the termination of the study or in an emergency situation. The specification 
of which group the subject was assigned to will be determined at the end of the study 
after reviewing and correlating the medication number with the record chart number. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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