Histological Evaluation of Healing Following Ridge Preservation Using a Composite Bovine Derived Xenograft or a Hydroxyapatite-Collagen Matrix
Phase: NA
Conditions: TEETH EXTRACTION
Sponsor: Datum Dental LTD

Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
Form CT 
UTHSA Clinical Trial Description 
This form is not mandatory. Other documents are acceptable if equivalent information is provided. 
UTHSCSA Tracking Number 
(internal use only) 
1. Original Version 
Date 
June 24, 2019 
1.1. Revision Date(s) 
add rows as needed 
 
 
2. Background 
Briefly discuss the important literature relevant to the trial and that provides background for the trial. Include the importance of the trial and any relevant 
treatment issues or controversies. 
Bone grafting following tooth extraction is often performed to preserve bony ridge dimensions adequate to support subsequent 
implant placement. Alveolar ridge resorption commonly occurs following tooth extraction, and the decrease in bone volume has 
the potential to make dental implant therapy impossible without surgery to reconstruct the ridge. The aim of ridge preservation 
grafting is to prevent or minimize this resorptive process, thereby preserving an adequate volume of bone for implant placement. 
Ridge preservation generally involves placement of a particulate bone graft material in the tooth socket, followed by use of a 
membrane or similar substance over the socket entrance to contain the bone graft. 
Various grafting materials have been recommended for these ridge preservation procedures, including cortical and cancellous 
freeze-dried bone allograft (FDBA), demineralized freeze-dried bone allograft (DFDBA), various xenografts, alloplasts and 
autografts. Our research group here in the Department of Periodontics at the UT Health Science Center at San Antonio has spent 
several years evaluating wound healing and clinical changes in ridge dimension following ridge preservation procedures using a 
variety of bone grafting materials and treatment protocols.(1-9) In most of these studies, bone allografts were used for ridge 
preservation. For various reasons, many clinicians prefer not to use human bone graft products, recommending use of xenografts 
or alloplastic materials instead. Our study group has previously examined use of various bovine xenografts. (1-10) 
Of interest are two composite materials that include either bovine bone or hydroxyapatite granules and sugar cross-linked 
collagen. These materials possess better handling properties that allow them to be used without the addition of a membrane 
during ridge preservation procedures. Two such composite materials are currently available in the U.S - a composite bovine 
xenograft with porcine collagen matrix and a hydroxyapatite graft with porcine sugar cross-linked type I collagen tendon matrix. 
The bovine/collagen matrix has been extensively researched for ridge preservation procedures. (11-17) 
The porcine collagen in the newer hydroxyapatite-containing composite graft material is cross linked with sugar with a 
proprietary technology (Glymatrix®). This cross-linking technology has shown promising results in its use as a membrane. (3, 18, 19). 
However, only a recent animal study presented as a poster at the 2017 Academy of Osseointegration on beagle dogs compared 
the two composite materials for a ridge restoration procedure. (20) The results of this animal study showed comparable healing 
and biocompatibility profiles, increased percentage of vital bone and a larger overall ridge restoration for the 
hydroxyapatite/collagen matrix. 
 
3. Objectives and Endpoints 
All data points collected in the study should support an objective or have a regulatory purpose. 
Complete the table – add rows as needed. 
3.1. Objective(s) 
Clearly and concisely define the primary and 
secondary outcomes. 
3.2. Endpoint 
Clearly define the endpoints. 
(endpoints are the basis for concluding that 
the objective has been met). 
3.3. Justification for Endpoint 
Briefly explain why the endpoint(s) were chosen. 
Is there a difference in histologic wound 
% vital bone formation, 
% vital bone formation shows the amount of 
healing following tooth extraction and 
% residual graft material, and 
new bone formed after the procedure. The 
ridge preservation between groups 
% “CT/other” (fibrous tissue and 
higher this % is the better the healing of the 
treated with Bio-Oss® 
marrow space) 
site 
Collagencompared to Ossix™ Bone 
% residual graft material shows how much of 
the graft material remained intact. Ideally all 
the graft materials should turn over to vital 
bone 
 
1 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
% CT/other (fibrous tissue and marrow space) 
is the amount of tissue that is neither native 
bone or graft material. It may be connective 
tissue that will mature to osteoid and bone or 
marrow space that is part of the normal 
healing. 
Change in ridge width; 
Change in buccal ridge height, and 
Change in lingual ridge height 
 
4. Rationale 
Briefly state the reason for conducting the clinical trial. 
A recent animal study presented as a poster at the 2017 Academy of Osseointegration on beagle dogs compared the two 
composite materials for a ridge restoration procedure. (20) The results of this animal study showed comparable healing and 
biocompatibility profiles, increased percentage of vital bone and a larger overall ridge restoration for the hydroxyapatite/collagen 
matrix. The proposed study will assess the histologic healing of this material in humans and compare it to a similar material that is 
well researched. 
 
 
5. Study Design 
5.1. Number of Groups/Arms 
2 
Group name(s) 
Activ
Test 
e contr
group 
ol group – Bio
– Ossix™ Bone
-Oss® Collagen 
5.2. Overall Design 
Select all applicable 
☒ Randomization 
☐
Cluster Randomized 
☐ Group-Sequential 
☐
Adaptive Design 
☒ Parallel Design 
☐
Placebo-Controlled 
☐ Superiority 
☐
Equivalence 
☐ 
Non-inferiority 
Device 
☐ Pilot 
☐
Pivotal 
☐ 
Post-Approval 
Drug/Biologic 
☐ Phase 1 
☐ Phase 1/2 
☐ 
Phase 2 
☐ 
Phase 2/3 
☐ Phase 3 
☒ 
Phase 4 
☐ Dose escalation 
If yes, details → 
☐ Dose ranging 
If yes, details → 
☐ Sub-studies 
If yes, details → 
5.3. Other Design Details: 
 
6. Study Population 
6.1. Study Population(s) 
Label/Name 
To add more populations – select a row, copy & 
paste 
6.2. Identify the criteria for inclusion 
The criteria that every potential participant must 
satisfy, to qualify for study entry. 
All individuals in this study population must meet 
all of the inclusion criteria in order to be eligible 
to participate in the study 
6.3. Identify the criteria for exclusion 
The characteristics that make an individual ineligible 
for study participation. 
All individuals in this study population meeting 
any of the exclusion criteria at baseline will be 
excluded from study participation. 
Dental patients needing extraction 
• 
One tooth, excluding molars, that 
has been identified by dental 
• 
Will not cooperate with the follow- 
up schedule. 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
faculty as requiring a single tooth 
extraction 
• 
A dental implant is indicated and 
treatment planned to replace the 
missing tooth 
• 
Have adequate restorative space 
for a dental implant-retained 
restoration 
• 
Have at least 10mm of alveolar 
bone height, without impinging on 
the maxillary sinus or inferior 
alveolar canal. 
• 
Have a dehiscence of the buccal or 
lingual bony plate of the tooth 
socket extending no more than 
50% of the total depth of the 
socket. 
• 
Female patients who have 
undergone a hysterectomy, tubal 
ligation, or menopause, and non- 
pregnant women of child-bearing 
potential. 
• 
Are nonsmokers or former 
smokers. Current smokers may be 
included if they smoke <10 
cigarettes per day 
• 
Patients will not be entered who 
are mentally incompetent, 
prisoners, or pregnant. 
• 
Pregnant women or women 
intending to become pregnant 
during the study period (as 
confirmed verbally; an over the 
counter pregnancy test will be 
provided if pregnancy status us 
unknown or suspected). 
• 
Patients who become pregnant 
during the study will be withdrawn 
and standard care will be delivered. 
• 
Smokers who smoke >10 cigarettes 
per day 
• 
Clinical and/or radiographic 
determinations which will preclude 
inclusion in this study are: Active 
infection other than periodontitis; 
Inadequate bone dimensions or 
restorative space for a dental 
implant; Presence of a disease 
entity, condition or therapeutic 
regimen which decreases 
probability of soft tissue and bony 
healing, e.g., poorly controlled 
diabetes, chemotherapeutic and 
immunosuppressive agents, 
autoimmune diseases, history of 
bisphosphonate use or long-term 
steroid therapy; Positive medical 
history of endocarditis following 
oral or dental surgery. 
6.4. 
Will screen failures be allowed to 
re-screen at a later date? 
☐ 
No 
☒ 
Yes 
If yes, describe criteria below ↓ 
Subjects who do not meet inclusion criteria initially may be re-screened and included in the 
study if inclusion criteria is met at a later date 
 
7. Study Intervention(s) being tested or evaluated 
This can include prevention, diagnostic or therapeutic interventions (e.g., drug or device) or educational, health services or basic science interventions (e.g., 
educational program, health care delivery model, or examining basic physiology) 
1) Active Control Group: Bio-Oss® Collagen, (Geistlich, Inc.), 90% bovine derived xenograft granules and 10% porcine collagen. 
2) Test Group: Ossix™ Bone (Datum Dental Ltd), a resorbable sponge-like matrix of 80% hydroxyapatite and 20% sugar cross- 
linked porcine collagen. 
 
8. Protocol-Directed procedures, items, services or tests 
List all procedures directed by the study plan - including items or services provided as part of routine or conventional care and those needed to diagnosis or treat 
research related complications. 
Important Note – The protocol directed procedures listed must match those in the Schedule of Activities (attachment) 
8.1. Drugs (trade and generic, dosage, route of administration) 
Either Amoxicillin 500mg three times per day for 7 days, or if they are allergic to penicillin/amoxicillin they will be prescribed 
Clindamycin 300mg three times per day for 7 days. Antibiotics will be used for an approved indication and are routinely 
prescribed as part of routine care. 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
8.2. Devices 
Bio-Oss® Collagen and Ossix™ Bone are both classified as devices by the FDA. Both will be used for an approved indication (in 
accordance with approved labeling). 
8.3. Biologics 
N/A 
8.4. Laboratory Tests 
If needed: An over-the-counter urine pregnancy test will be provided to female subjects and self-administered in the graduate 
periodontics clinic of UTHSCSA. A negative result is required to enter the study. 
Histology of the core bone biopsy 
8.5. Imaging Procedures 
8.6. Other Research Procedures (e.g., other safety and efficacy assessments.) 
1) Impressions of the arch with tooth to be extracted; 2) fabrication of a ridge measurement stent; 3) tooth extraction & ridge 
preservation; 4) dental implant placement & core bone biopsy; 6) bone quality determination (Lekholm and Zarb classification); 
8.7 Attach a Schedule of Activities (SOA) Excel File [Download the Template here: Schedule of Activities] 
Check to indicate that the 
SOA Excel File is attached → 
☒ 
8.8 Description of Methods (or include in separate document) 
Check to indicate that the 
Methods are described in an 
attached file→ 
☐ 
Each extraction socket will receive one 5 X 5 X 8mm or 5 X 5 X 10mm graft cube (research) with no attempt to fill the entire 
socket. No wound dressing or membrane will be used to cover the bone graft material as both materials can be used alone. All 
extraction sockets will be sutured with Vicryl 4.0 mattress suture which will be removed approximately 2 weeks (+ 1 week) after 
the procedure as per standard of care. All patients will be prescribed an oral antibiotic after the procedure either Amoxicillin 
500mg three times per day for 7 days, or if they are allergic to penicillin/amoxicillin they will be prescribed Clindamycin 300mg 
three times per day for 7 days as per standard of care. 
In keeping with the protocol our study group has used several times before, the plan will be to extract non-molar teeth and graft 
with the test/control materials. Each subject will provide a single non-molar tooth site for study treatment. Following approx. 14 
weeks of healing, we will harvest a core biopsy at the time of implant placement. The core biopsy will then be evaluated for the 
primary outcomes: % vital bone formation, % residual graft material, and % “CT/other” (fibrous tissue and marrow space). We 
will also evaluate the following secondary outcomes using a custom measuring stent for each subject: change in ridge width; 
change in buccal ridge height, and change in lingual ridge height. During the 14-week healing period, subjects will be followed up 
with biweekly and monthly visits as per standard of care, to evaluate healing. 
A detailed visit by visit outline is provided below: 
Step-by-Step Methods: All the procedures are routinely performed in the graduate periodontics clinic as part of standard care. 
The methodology is the same previous studies of our group HSC20130470H, HSC20150708H, HSC20170339H, HSC20170267H, 
among others. 
Visit 1 - Screening examination: 
If a patient presents at a consultation appointment at the graduate periodontics clinic with a non-molar tooth (incisors, canines, 
premolars) that needs to be extracted and replaced with a dental implant, the treating doctor will provide: 
• 
Explanation to the patient of the purposes of the study and the planned procedures related to the study. 
• 
Explanation to the patient of the risks, benefits and possible complications of participation in the study. 
• 
Notification to the patient that inclusion in the study is voluntary and conditional upon satisfying the inclusion and 
exclusion criteria. 
Patient will be given the opportunity during the appointment to ask any question that he/she may have. Following an 
informational discussion with the prospective subject, consent will be obtained within 2 weeks. This is up to the discretion of the 
patient. If the patient would like to become a subject for entry into the study, he or she can do so immediately, or can consider it 
for up to 2 weeks (must be prior to extraction). 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
Visit 2 – Extraction with ridge preservation using either 90% bovine derived xenograft granules and 10% porcine collagen (Bio- 
Oss® Collagen, Geistlich, Inc.) or a resorbable sponge-like matrix of 80% hydroxyapatite and 20% sugar ross-linked porcine 
collagen (Ossix™ Bone, Datum Dental Ltd). 
The patient will be assigned to either group by simple randomization with a 1:1 ratio 
If the patient has agreed to participate in the study, informed consent will be obtained and documented on a written consent 
form. If not, standard care treatment will be provided to the patient, but the patient would not be included in the study. 
On the day of the planned extraction, the medical history will be updated. 
Pregnant women or women intending to become pregnant during the study period: Prior to dental surgery, females of child- 
bearing age are asked verbally if there is any possibility that they are pregnant. If not, we proceed with surgery and no pregnancy 
test is done. If the woman states that there is a possibility that she is pregnant, an over the counter urine pregnancy test to rule 
pregnancy in or out will be provided. Use of the urine pregnancy test is only done if she says she may be pregnant. [If needed: 
Urine pregnancy test will be provided to female subjects in the graduate periodontics clinic of UTHSCSA and a negative result is 
required to enter the study.] 
Impressions of the arch with the tooth to be extracted in place will be taken prior to extraction and poured in stone to obtain 
initial study casts (research). If the tooth to be extracted is fractured, a wax-up of the tooth will be made before the stent is 
fabricated (research). 
One measurement stent will be fabricated to facilitate clinical ridge measurements. A clear suck-down resin measuring stent will 
be fabricated in the laboratory to allow standardization of the location of clinical measurements of ridge width and height 
through small holes that will be placed in the stent at the time of tooth extraction. 
The width of keratinized tissue will be recorded clinically to the nearest 0.5mm using a periodontal probe at the mid-buccal and 
mid-lingual sites of the tooth to be extracted. 
A pre-operative periapical radiographic image will be taken before the extraction as per standard of care (if not already 
available). 
At the time of surgery, local anesthesia will be administered. Conscious sedation will be administered according to patient need 
and investigator preference, per standard care. Buccal and lingual flaps will be minimally reflected to a point up to 3mm apical to 
the bony crest. 
Prior to tooth extraction, the clinical measuring stent will be placed and measurements of ridge width and ridge height will be 
taken and recorded to the nearest 0.5mm. Ridge width will be measured to the nearest 0.5mm using a ridge caliper at a point 
approximately 4mm apical to the facial and lingual bony crest through small holes created in the stent at those locations. Ridge 
height will be measured to the nearest 0.5mm through two holes in the occlusal aspect of the stent – one hole directly above the 
facial bony crest and another hole directly above the lingual bony crest. This stent will be retained for use during the subsequent 
implant placement surgery. 
Tooth extraction will be performed as atraumatically as possible. Following tooth extraction, a final determination of enrollment 
into the study will be conducted based on the integrity of the buccal bone wall plate at the extraction site. If the buccal plate is 
intact, defined as no bony dehiscence greater than 50% of the socket depth, the patient will remain enrolled in the study. 
Conversely, if the buccal plate integrity has not been maintained (bony dehiscence >50%) the patient will be exited from the 
study and standard care therapy will be delivered to the patient. 
After extraction, the number of bony walls in each socket will be recorded along with the presence of any bony dehiscences or 
fenestrations. Buccal and lingual flap elevation will be minimized and will extend no more than 2-3mm beyond the bony crest on 
the facial and lingual surfaces. The buccal plate thickness will be measured using an Iwanson gauge positioned perpendicular to 
the inner wall of the extraction socket. One beak of the gauge will be placed within the extraction socket 1.0mm apical to the 
alveolar bone crest. The other beak will be placed on the external bone surface. This buccal plate thickness measurement will be 
recorded to the nearest 0.1 mm. 
The socket will be thoroughly debrided, a 5 X 5 X 8 mm or 5 X 5 X 10 mm bone graft cube of either 90% bovine derived xenograft 
granules and 10% porcine collagen (Bio-Oss® Collagen, Geistlich, Inc.) or a resorbable sponge-like matrix of 80% hydroxyapatite 
and 20% sugar cross-linked porcine collagen (Ossix™ Bone, Datum Dental Ltd) will be soaked in patient's blood and inserted in the 
socket. No attempt will be made to completely fill the socket as the materials expand after they contact fluids. No membrane or 
wound barrier will be placed over the graft in either group. Vicryl 4.0 sutures will be placed over the graft material to secure it in 
place as part of standard of care. Primary closure will not be attempted. 
Visit 3 - Post-operative visit 
The post-operative visit after extraction/ridge preservation will be scheduled approximately 3 weeks (±1 week) after the 
procedure. If needed, an optional POT visit may be scheduled before this visit, per standard care and as determined by patient 
need. 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
Visit 4 - Pre-implantation: 
Approximately 3 months after the extraction (± 2 weeks) a CBCT of the prospective implant site may be taken as needed per 
standard care. The implant surgery will ensue within 2 weeks (± 2 weeks). The CBCT is not part of the study but rather standard of 
care. 
Prior to surgery, pregnancy status will be confirmed verbally. An over the counter pregnancy test will be provided if pregnancy 
status us unknown or suspected (research). A negative result is required to continue being in the study. 
Visit 5 - Implant placement: 
Prior to surgery, pregnancy status will be confirmed verbally. An over the counter pregnancy test will be provided if pregnancy 
status us unknown or suspected (research). A negative result is required to continue being in the study. 
Approximately 16 weeks (±2 weeks) after the extraction, implant surgery will be performed (standard of care). The width of 
keratinized tissue will be measured at the prospective implant site. A piece of floss will be run over the keratinized tissue and cut 
to the width of keratinized tissue, i.e. from the mucogingival junction (MGJ) on the buccal to the MGJ on the lingual. The floss will 
be then measured with a ruler to the closest 0.5mm. 
After local anesthesia (and conscious sedation if requested), the patient will undergo implant placement surgery at the previously 
extracted tooth site and if required simultaneous guided bone regeneration (GBR) will be performed as per standard care. First, 
the individual subject’s measuring stent and caliper will be used to determine the ridge width and ridge height at the same 
locations as done in the tooth extraction/grafting surgery visit. During the implant bed preparation, a hollow drill will be used to 
allow retrieval of a bone core which will be collected and stored in formalin and subsequently examined histologically and 
outcomes including percentages of new bone formation, residual graft and connective tissue/other will be recorded. 
• 
During the implant placement procedure, the following data will be recorded per standard care: 
• 
Bone quality according Lekholm and Zarb (1985) classification 
• 
Absence/Presence of bone defect, including dehiscence or crater like defect. If present, at what site(s) (Buccal, Mesial, 
Lingual, Distal) and what are the respective depth and width of these defects. 
• 
Absence/Presence of bone fenestration. If present what is the size of the fenestration in height and width. 
• 
Was additional bone grafting needed in case of thin bone or dehiscence of threads? Yes/No 
Subject participation ends at the time of implant placement. However, standard care post-operative visits will be provided after 
implant placement. Generally, one or two post-operative visits will be provided during the first month after implant surgery to 
insure adequate healing. 
 
 
9. 
Preparation/Handling/ Storage/Accountability of Investigational Drug, Biologic, or Device 
N/A - This study does not include any investigational products (e.g. drugs, devices or biologics) 
N/A - An Investigator Brochure is attached 
N/A - A Drug/Device Manual is attached 
☒ 
☐ 
☐ 
9.1. Acquisition and accountability 
State how the study intervention and control product will be provided to the investigator. Describe plans about how and by whom the study intervention will be 
distributed, including participation of a drug repository or pharmacy, and plans for disposal of expired or return of unused product. 
9.2. Formulation, Appearance, Packaging, and Labeling 
Describe the formulation, appearance, packaging, and labeling of the study intervention and control product, as supplied. Information in this section can usually 
be obtained from the IB or the package insert, or device labeling. This section should include the name of the manufacturer of the study intervention and control 
product. 
9.3. Product Storage and Stability 
Describe storage and stability requirements (e.g., protection from light, temperature, humidity) for the study intervention and control product. For studies in which 
multi-dose vials are utilized, provide additional information regarding stability and expiration time after initial use (e.g., the seal is broken). 
9.4. Preparation 
Describe the preparation of the study intervention and control product, including any preparation required by study staff and/or study participants. Include 
thawing, diluting, mixing, and reconstitution/preparation instructions in this section. For devices, include any relevant assembly or use instructions. 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
 
 
10. Study Intervention Additional Details 
10.1. Measures to Minimize Bias: Randomization and Blinding 
This section should contain a description of randomization and blinding procedures (if applicable to the study design). It should include a description or a table that 
describes how study participants will be assigned to study groups, without being so specific that blinding or randomization might be compromised. Plans for the 
maintenance of trial randomization codes and appropriate blinding for the study should be discussed. The timing and procedures for planned and unplanned 
breaking of randomization codes should be included. Include a statement regarding when unblinding may occur and who may unblind. Provide the criteria for 
breaking the study blind or participant code. Discuss the circumstances in which the blind would be broken for an individual or for all participants (e.g., for serious 
adverse evets (SAEs)). Indicate to whom the intentional and unintentional breaking of the blind should be reported. 
22 envelopes will be prepared for each arm in a simple randomization 1:1 ratio, sealed and shuffled. The faculty staffing 
the procedure will draw an envelope from the stack prior to the surgical procedure appointment. Since the outcome of the study 
is the histologic healing, blinding of the surgeon is not necessary. 
10.2. Study Intervention Compliance 
Define how adherence to the protocol (e.g., administration of study intervention, use of device,) will be assessed, and verified (if applicable, e.g., plasma assays, 
electronic monitoring devices, daily diaries). 
 
Patients will need to be present at each scheduled visit. Failure to attend any of the visits will result in exit from the study. All 
providers placing test and control materials as part of the study intervention will be trained and provided with detailed 
instructions to ensure methods are consistent and in compliance with the protocol. All faculty staffing residents are familiar with 
the study protocol and are able to verify the results of the procedure and measurements taken. 
10.3. Permitted Concomitant Therapy 
This section should be consistent with the medication restrictions in the inclusion/exclusion criteria previously listed. Describe how allowed concomitant therapy 
might affect the outcome (e.g., drug-drug interaction, direct effects on the study endpoints). 
N/A 
 
 
10.4. 
Rescue Medicine 
List all medications, treatments, and/or procedures that may be provided during the study for “rescue therapy” and relevant instructions. 
☒ 
N/A, no rescue medicine 
 
 
 
 
11. Study Intervention Discontinuation 
11.1. Discontinuation of Study Intervention 
Describe the criteria for discontinuing the study intervention (e.g., halting rules), including any monitoring test(s) and associated clinical decision point(s). Include 
reasons for temporary discontinuation of the study intervention (e.g., type and quantity of adverse events), clearly stating the length of time, if applicable, and 
describe the data to be collected at the time of study intervention discontinuation and approaches for restarting administration of or re-challenging with study 
intervention. 
Study will be discontinued if more than 5% of subjects present an adverse reaction such as infection or material recall. Such a 
reaction would be extremely rare as the study material is FDA approved and in the US market since 2016. 
11.2. Continued Follow-up Discontinuation of Study Intervention 
Describe efforts that will be made to continue follow-up of participants who discontinue the study intervention, but remain in the study for follow-up, especially for 
safety and efficacy study endpoints (if applicable). Reasonable efforts must be made to undertake protocol-specified safety follow-up procedures to capture 
adverse events (AE), serious adverse events (SAE), and unanticipated problems involving risks to subjects or others (UPIRSOs). 
All patients that participate in the study, including those discontinued due to adverse reactions, will be followed until completion 
of the study or resolution of the adverse reaction (unless consent has been withdrawn). 
 
 
12. Statistical Considerations 
12.1. Statistical Hypotheses 
State the formal and testable null and alternative hypotheses for primary and key secondary endpoints, specifying the type of comparison (e.g., superiority, 
equivalence or non-inferiority, dose response) and time period for which each endpoint will be analyzed. 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
Hypotheses: a.) No difference in % vital bone, % residual graft and % connective /other tissues between BioOss Collagen and 
Ossix Bone groups. b.) No dimensional differences in alveolar ridge after ridge preservation with BioOss Collagen or Ossix Bone. 
12.2. Sample Size Determination 
Include number of participants to recruit, screen, and enroll to have adequate power to test the key hypotheses for the study. Provide all information needed to 
validate your calculations and judge the feasibility of enrolling and following the necessary number of participants. 
Power analysis revealed a sample size of 14 patients per group was enough to detect a mean difference in percentage of new 
bone formation of 1 SD by Mann-Whitney U test at the 0.05level with a power of 88.5%. Anticipating a potential 30% dropout 
rate and needing 14 fully compliant patient per treatment group, 22 patients will be enrolled in each group. 
12.3. Populations for Analyses 
Clearly identify and describe the analysis datasets (e.g., which participants will be included in each). 
All study participants who complete the study intervention will be included in the analysis for all outcome measures. 
12.4. Statistical Analyses 
Include analysis of primary efficacy endpoints, secondary endpoints, safety analyses, and any planned interim analyses 
The outcomes of the histologic and clinical parameters will be summarized with the sample size, mean, standard deviation, 
median, minimum and maximum. The significance of variation in the mean with group BioOss collagen or Ossix Bone will be 
assessed with two-sample t-testing. The significance of variation in the group effect with another variable will be assessed with 
an interaction term in a linear model. All statistical testing will be two-sided with a significance level of 5%. Spearman rank and 
Pearson correlations between clinical parameters and histologic parameters will be analyzed as well. All statistical analyses will be 
done with statistical software. 

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Composite Bovine Derived Xenograft or a Hydroxyapatite-Sugar Cross Linked Collagen Matrix 
 
References: 
 
1. 
Beck TM, Mealey BL. Histologic analysis of healing after tooth extraction with ridge preservation using 
mineralized human bone allograft. J Periodontol. 2010;81(12):1765-72. 
2. 
Borg TD, Mealey BL. Histologic healing following tooth extraction with ridge preservation using mineralized 
versus combined mineralized-demineralized freeze-dried bone allograft: a randomized controlled clinical trial. J 
Periodontol. 2015;86(3):348-55. 
3. 
Cook DC, Mealey BL. Histologic comparison of healing following tooth extraction with ridge preservation using 
two different xenograft protocols. J Periodontol. 2013;84(5):585-94. 
4. 
Coomes AM, Mealey BL, Huynh-Ba G, Barboza-Arguello C, Moore WS, Cochran DL. Buccal bone formation after 
flapless extraction: a randomized, controlled clinical trial comparing recombinant human bone morphogenetic protein 
2/absorbable collagen carrier and collagen sponge alone. J Periodontol. 2014;85(4):525-35. 
5. 
Eskow AJ, Mealey BL. Evaluation of healing following tooth extraction with ridge preservation using cortical 
versus cancellous freeze-dried bone allograft. J Periodontol. 2014;85(4):514-24. 
6. 
Hoang TN, Mealey BL. Histologic comparison of healing after ridge preservation using human demineralized 
bone matrix putty with one versus two different-sized bone particles. J Periodontol. 2012;83(2):174-81. 
7. 
Whetman J, Mealey BL. Effect of Healing Time on New Bone Formation After Tooth Extraction and Ridge 
Preservation With Demineralized Freeze-Dried Bone Allograft: A Randomized Controlled Clinical Trial. J Periodontol. 
2016;87(9):1022-9. 
8. 
Wood RA, Mealey BL. Histologic comparison of healing after tooth extraction with ridge preservation using 
mineralized versus demineralized freeze-dried bone allograft. J Periodontol. 2012;83(3):329-36. 
9. 
Frost NA BA, Galloway PB, Huynh-Ba G, Mealey BL. . The Decision-Making Process for Ridge Preservation 
Procedures Following Tooth Extraction. Clinical Advances in Periodontics 2014;4:56-63. 
10. 
Corning PJ, Mealey BL. Ridge preservation following tooth extraction using mineralized freeze-dried bone 
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