Antibiotics Prior to Mini-screw Implant Insertion

Study Overview
=================
Brief Summary
-----------------
The investigators plan to use amoxicillin in capsule form, prepared by a pharmacist, for antibiotic prophylaxis to decrease the failure rate of mini-screw implants temporarily placed in the palate of patients involved in Phase II orthodontics treatments. The mini-screws will be 8 mm long 1.7 mm diameter titanium screws manufactured by Forestadent and are commercially available and currently widely used in orthodontic treatment in both private practice and educational settings. Since antibiotic prophylaxis is considered the standard of care with traditional dental implants, the investigators believe that such prophylaxis will decrease the failure rate of orthodontic mini-screw implants also.

Detailed Description
-----------------
Subjects will be selected for the study based on treatment plans for Phase II orthodontics at Saint Louis University Center for Advanced Dental Education orthodontics program, which require the use of palatally placed mini-screw implants for anchorage control. If the patient is at or beyond the age of 18 years, they will be approached about this study. If the patient is under the age of 18 years, the parent or legal guardian of the patient will be approached. After the consult is completed, where the treatment plan has been explained and standard consent forms have been signed, a member of the research team will verbally confirm with the patient or the patient and parent/guardian that the patient cannot be excluded from the study based on exclusion criteria from the patient's medical history. Orthodontic treatment at SLU CADE involves monthly visits to the orthodontic clinic where patients receive orthodontic treatment, including leveling and aligning of teeth with archwires and fixed appliances on teeth, space closure, occlusion correction, and finishing and detailing. Mini-screw placement is not necessary nor included in all treatment plans given at SLU CADE orthodontics. The possible subjects for the study will patients who will receive mini-screw implants as a course of their treatment for orthodontic anchorage (standard of care). Participants will be weighed so that appropriate dosing can be ensured and randomized 1:1 to receive either and antibiotic (Amoxicillin) or a placebo (glucose) 1 hour prior to mini-screw insertion (research related). Patients weighing less than 40 kg will be given 50mg/kg. The Amoxicillin and the placebo (glucose) will be prepared in capsule form by a pharmacist and made to look identical. The Amoxicillin or placebo will be dispensed at CADE and taken at CADE 1 hour prior to the procedure. Standard procedure for dispensing Amoxicillin at SLU CADE is to draw appropriate dosage from the dispensary and provide Amoxicillin to at risk patients prior to invasive dental procedures, in accordance with prophylaxis guidelines set form by the American Heart Association. Documentation of dosage and time of dispensing is noted in the patient record. However, in this study, documentation in the patient dental record will only reflect that either a placebo or Amoxicillin was given as part of a randomized controlled trial. Standard of care for orthodontic mini-screw implants includes oral hygiene instructions and 1 week of oral antibiotic mouth rinse use (.12% Chlorhexidine) and all participants in this study will follow standard of care in addition to the administration of either placebo or antibiotic. Randomization between control or experimental group will be conducted by the Research Chair, Hiroshi Ueno, and the PI will have no knowledge of to which group subjects are assigned. Participants will be followed at time of mini-screw placement (T0), 1 month post procedure (T1), 3 months post-procedure (T2), and 6 months post-procedure (T3). The participant has standard of care appointments at these time points, so there are not any extra visits for research purposes. At these appointment, participants will undergo an intra-oral exam to determine mobility of the mini-screw(s), to check for inflammation at the site of mini-screw placement, assess oral hygiene at the site of mini-screw placement, and be asked to rate both their pain and tenderness related to the mini-screw. Pain is defined as spontaneous pain frim the mini-screw site. Tenderness is defined as pain resulting from palpation of the mini-screw. Mobility will be determined by placing a small amount of force on the mini-screw with a cotton plier. The amount of mobility will be assessed as having no mobility (Grade 0), having between 0mm and 1 mm of mobility (Grade 1), or having more than 1 mm of mobility (Grade 2). Inflammation will be assessed as having no redness or swelling at the site (Grade 0), having redness only at the site (Grade 1), or having both redness and swelling (Grade 2). Oral hygiene will be assessed as having no visible plaque at the site (Grade 0), having small amounts of plaque at the site (Grade 1), or having moderate to large amounts of plaque at the site (Grade 2). Pain and tenderness will be evaluated separately and will be assessed by asking the patient to rate their pain level on a scale of 0 to 10, 0 being no pain and 10 being unbearable, excruciating pain. A member of the research team will make these evaluations at each time point. All five of these would be assessed as part of the standard of care for mini-screw placement, regardless of participation in the research study or lack thereof. The only action related to the research that is not standard of care is the dispensing of either the antibiotic or the placebo at 1 hour prior to mini-screw placement. Success of the mini-screw will be defined as number of survival with Mobility Grade 0 or 1 & No Pain & Inflammation Grade 0 or 1. Failure of the mini-screw will be immediately determined as failed if the mini-screw is not present at one of the time points or upon an assessment of Grade 2 mobility. Grade 2 mobility will result in removal of the mini-screw. If the mini-screw implants fail, the participants will have the mini-screw removed. It is up to assigned instructors as to whether or not mini-screws will be replaced. If the mini-screws will not be replaced, the patient will be removed from the study, but all data collected will be included in the research. Standard of Care will be followed in all instances at time points T(0), T(1), T(2) and T(3). The dependent variable will be success or failure, while the independent variable will be antibiotic prophylaxis or placebo. Failure will be defined as mobile or lost MSIs, and success will be defined as stability of the MSIs maintained after 6 months. 8mm long, 1.5 mm diameter, palatally placed MSIs provided by a single manufacturer (Forestadent) that are immediately force loaded or delayed in force loading will be included in the study. Data will be analyzed with SPSS for Windows (SPSS Inc., Chicago, Ill). A Chi Square test for independence will be used to determine association, if any, between the two categorical variables. This study will establish an alpha of 0.05 and a beta of 0.08322, and to achieve power of 0.91, a sample size of 100 subjects is the goal for recruiting.

Official Title
-----------------
Antibiotic Prophylaxis Prior to the Insertion of Orthodontic Mini-screw Implants: a Randomized Controlled Trial

Conditions
-----------------
Inflammation at Mini-screw Insertion Site, Mobility, Mini-screw

Intervention / Treatment
-----------------
* Drug: Amoxicillin
* Drug: Placebo oral capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects will be selected for the study based on treatment plans for Phase II orthodontics at SLU CADE orthodontics program, which require the use of palatally placed mini-screw implants for anchorage control. Exclusion Criteria: Patients with experience in previous MSI placements allergy to amoxicillin allergy to Beta-lactam based antibiotics medical syndrome diagnoses psychiatric disorders (ADHD, autism, manic-depressive disorder, etc.) a compromised immune system impaired or decreased kidney function Type I or Type II diabetes patients taking Probenicid or Allopurinol

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will be a double-blind randomized control trial in which half the participants will be given two grams of amoxicillin in capsule form, prepared by a pharmacist, and the other half will be given a placebo in capsule form, prepared by a pharmacist, 1 hour prior to MSI placement. Sealed envelopes containing either antibiotics or placebo capsules will be given to patients, with only the research committee chair knowing which patients are in the control group (placebo) and which are in the experimental group (antibiotics). Test subjects will be followed for 1 month (T1), 3 months (T2), 6 months (T3) following placement of MSIs.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>All participants will be weighed. This group will receive a placebo (glucose) 1 hour prior to insertion of mini-screw implants. | Drug: Placebo oral capsule<br>* see previous descriptions<br>|
| Experimental: Experimental Group<br>All participants will be weighed so that appropriate dosing can be ensured and will receive 2 grams of Amoxicillin 1 hour prior to mini-screw insertion. Patients weighing less than 40 kg will be given 50mg/kg of Amoxicillin. | Drug: Amoxicillin<br>* see previous descriptions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-screw implant success or failure | Participants will undergo an intra-oral exam to determine mobility of the mini-screw(s), to check for inflammation at the site of mini-screw placement. Mobility will be determined by placing a small amount of force on the mini-screw with a cotton plier. The amount of mobility will be assessed as having no mobility (Grade 0), having between 0mm and 1 mm of mobility (Grade 1), or having more than 1 mm of mobility (Grade 2). Inflammation will be assessed as having no redness or swelling at the site (Grade 0), having redness only at the site (Grade 1), or having both redness and swelling (Grade 2). Success of the mini-screw will be defined as number of survival with Mobility Grade 0 or 1 & No Pain & Inflammation Grade 0 or 1. Failure of the mini-screw will be immediately determined as failed if the mini-screw is not present at one of the time points or upon an assessment of Grade 2 mobility. Grade 2 mobility will result in removal of the mini-screw. | T(0) at time of insertion | 
| Mini-screw implant success or failure | Participants will undergo an intra-oral exam to determine mobility of the mini-screw(s), to check for inflammation at the site of mini-screw placement. Mobility will be determined by placing a small amount of force on the mini-screw with a cotton plier. The amount of mobility will be assessed as having no mobility (Grade 0), having between 0mm and 1 mm of mobility (Grade 1), or having more than 1 mm of mobility (Grade 2). Inflammation will be assessed as having no redness or swelling at the site (Grade 0), having redness only at the site (Grade 1), or having both redness and swelling (Grade 2). Success of the mini-screw will be defined as number of survival with Mobility Grade 0 or 1 & No Pain & Inflammation Grade 0 or 1. Failure of the mini-screw will be immediately determined as failed if the mini-screw is not present at one of the time points or upon an assessment of Grade 2 mobility. Grade 2 mobility will result in removal of the mini-screw. | T(1) at 1 month post-placement | 
| Mini-screw implant success or failure | Participants will undergo an intra-oral exam to determine mobility of the mini-screw(s), to check for inflammation at the site of mini-screw placement. Mobility will be determined by placing a small amount of force on the mini-screw with a cotton plier. The amount of mobility will be assessed as having no mobility (Grade 0), having between 0mm and 1 mm of mobility (Grade 1), or having more than 1 mm of mobility (Grade 2). Inflammation will be assessed as having no redness or swelling at the site (Grade 0), having redness only at the site (Grade 1), or having both redness and swelling (Grade 2). Success of the mini-screw will be defined as number of survival with Mobility Grade 0 or 1 & No Pain & Inflammation Grade 0 or 1. Failure of the mini-screw will be immediately determined as failed if the mini-screw is not present at one of the time points or upon an assessment of Grade 2 mobility. Grade 2 mobility will result in removal of the mini-screw. | T(2) at 3 months post-placement | 
| Mini-screw implant success or failure | Participants will undergo an intra-oral exam to determine mobility of the mini-screw(s), to check for inflammation at the site of mini-screw placement. Mobility will be determined by placing a small amount of force on the mini-screw with a cotton plier. The amount of mobility will be assessed as having no mobility (Grade 0), having between 0mm and 1 mm of mobility (Grade 1), or having more than 1 mm of mobility (Grade 2). Inflammation will be assessed as having no redness or swelling at the site (Grade 0), having redness only at the site (Grade 1), or having both redness and swelling (Grade 2). Success of the mini-screw will be defined as number of survival with Mobility Grade 0 or 1 & No Pain & Inflammation Grade 0 or 1. Failure of the mini-screw will be immediately determined as failed if the mini-screw is not present at one of the time points or upon an assessment of Grade 2 mobility. Grade 2 mobility will result in removal of the mini-screw. | T(3) at 6 months post-placement | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TADs, antibiotics, prophylaxis, temporary anchorage devices, mini-screw implants, MSIs, failure rate