Changes of Soft and Hard Tissues After Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot

• Sponsor: University of Manitoba (Other)
• Overall Status: Completed
• CT.gov ID: NCT03331185
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

A Clinical Trial to study the effectiveness between two, tooth socket grafting materials namely, Freeze Dried Bone Allograft (human derived bone particles) and Leukocytic-Platelet Rich Fibrin (the patient's own centrifuged blood).

The purpose of this study is to compare the effects (good and bad) of Bone Allograft to Platelet Rich Fibrin to see which material would be the most effective in maintaining the volume of the gum and bone of the jaw during the healing phase as well as minimizing the amount of pain and/or swelling following tooth extraction.

Condition or Disease	Intervention/Treatment	Phase
Alveolar Bone Loss; Tooth Loss	Biological: Freeze Dried Bone Allograft; Biological: L-PRF clot	Phase 2/Phase 3

Detailed Description

A prospective,randomized clinical trial will be conducted to determine whether L-PRF, compared to freeze dried bone allograft, will result in comparable volumetric shrinkage of the alveolar ridge and overlying keratinized tissue, following extraction of teeth and socket grafting.

This trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. The participants will be randomly assigned to two groups. The surgical procedure will be performed by one of five calibrated periodontal residents.

Patients will be followed for 2 weeks post-operatively by the same resident, to monitor the healing process and to assess for any complications.

Randomization will be achieved using a computerized randomization scheme and will be assigned to one of two groups and allocated by means of a sealed envelope opened on the day of surgery communicated to the surgeon during the surgery by a supervising faculty member. Participants will be block-randomized for each of the 5 operators for balance.

Anesthesia will be achieved and soft tissue measurements will be obtained using a periodontal probe. An atraumatic extraction technique will be performed to allow for minimal disturbance of the soft and hard tissue architecture.

The extraction socket walls are then assessed and any defects in socket measured with a periodontal probe. Group A: Full thickness mucoperiosteal pouch is created up to ~3mm apical of the bony crest of the socket with a periosteal elevator. The socket is incrementally filled with mineralized cortical freeze-dried bone allograft and condensed. Group B: Socket is pouched as in group A followed by venipuncture of the antecubital vein with 21G needle and collection of 4-6 vials (10ml each) of venous blood without any additive or anticoagulant. The vials are centrifuged for 12 minutes at 2700 rpm to form L-PRF clots. The socket is incrementally filled with the clots and condensed.

Following socket fill, both groups will have the grafts covered by dense polytetrafluoroethylene membrane. The membrane is trimmed and adapted with the borders tucked 2-3mm underneath the gingival tissues. Tissues, graft and membrane are stabilized with 5/0 PTFE sutures.

The patients will also receive a pain VAS questionnaire evaluating the post-operative pain 1 and 7 days following surgery. A CBCT with the radiographic stent will be taken within 72 hours of the surgery.

7 days post-op: Sutures will be removed if deemed suitable. The VAS questionnaire will be collected.

6 weeks post op: d-PTFE membrane will be retrieved and discarded using tissue forceps. Alginate impressions will be taken for a surgical guide.

11 weeks post op: Second CBCT will be taken with radiographic surgical stent. Images obtained will be used to analyze and compare the ridge dimensions to those obtained at baseline as well as for surgical implant planning.

12 weeks post op: Soft tissue measurement with periodontal probe and floss spanned over edentulous site from buccal to lingual mucogingival junction. Implant placement will be done per standard procedure. A 2.5mm diameter trephine drill will be used to harvest a bone core for histologic analysis. The bone core will be immediately submerged in a solution of 10% neutral buffered formalin. Osteotomies and implant placement will be done following the manufacturer's protocol. Depending on the buccal bone and soft tissue thickness, ancillary soft tissue augmentation, bone augmentation or combination of these procedures may be indicated. The patient will be followed up and referred to the restorative dentist as per standard procedure. Photographs will be taken at every visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A prospective,randomized clinical trial will be conducted. The trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. 42 participants will be randomly assigned to two groups and a direct comparison will be made between the results obtained from the two groups.A prospective,randomized clinical trial will be conducted. The trial aims at obtaining information to determine which material would provide a superior clinical result, as well as reporting on patient related outcomes. 42 participants will be randomly assigned to two groups and a direct comparison will be made between the results obtained from the two groups.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dimensional Changes of Soft and Hard Tissues Following Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot Covered With d-PTFE Membrane: A Randomized Clinical Trial
• Actual Study Start Date: Jan 3, 2018
• Actual Primary Completion Date: Apr 2, 2019
• Actual Study Completion Date: Apr 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Freeze Dried Bone Allograft Socket filled with Mineralized Cortical Freeze Dried Bone Allograft	Biological: Freeze Dried Bone Allograft; Human derived bone particles used in oral and periodontal grafting procedures; Other Names: FDBA
Experimental: L-PRF Clot Socket filled with L-PRF Clot	Biological: L-PRF clot; L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.; Other Names: Leukocytic Platelet Rich Fibrin Clot

Outcome Measures

Primary Outcome Measures

1. Overall Horizontal Change in Alveolar Ridge Width [Difference reported on horizontal changes comparing CBCT analysis 11weeks after extraction and grafting compared to CBCT following extraction and grafting]

   Calculated mean of post operative CBCT measurements of horizontal alveolar bone width changes following extraction and alveolar ridge preservation.

Secondary Outcome Measures

1. Buccolingual Change in Width of Keratinized Soft Tissue [Soft tissue measurement at time of extraction and grafting and 12 weeks after extraction and grafting]

   Difference in post operative measurement analysis of keratinized gingiva changes following extraction and alveolar ridge preservation

2. Post-operative Pain and Swelling [Measured at 7 days following extraction and grafting]

   Post-operative pain and complications measured by VAS-questionnaire obtained following extraction and grafting. The VAS-questionnaire contained the following categories to be answered 7days post-operatively: Pain, Swelling. A visual line scale of 100mm in length was provided with no pain/swelling on the one end and severe pain/swelling on the opposite end. Participants were instructed to rate their pain and swelling by marking a single line on the scale indicating the degree of pain/swelling they experienced. Markings were physically measured on the scale and converted into a score with 0 representing no pain/swelling and 1 representing severe pain/swelling.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects with molars or premolars indicated for extraction.

• Patients that present with a post extraction class I and II socket (<30% bone loss on the buccal or lingual plate, measured from the most coronal aspect of intact bone to the most apical aspect of the defect divided by the measurement from the most apical aspect of the defect to the apex of the socket x 100).

• Patients presenting with the need for single extractions.

• Patients with general good health that does not have a condition contra-indicating routine dental treatment, extraction and implant placement.

• Patients that are compliant with the research protocol and methods.

• Patients that have read, understood and signed an informed consent form.

Exclusion Criteria:

• Extraction and ridge preservation indicated for teeth other than premolars and molars.

• Patients that present with a post extraction class III socket (>30% bone loss on the buccal or lingual plate, measured from the most coronal aspect of intact bone to the most apical aspect of the defect divided by the measurement from the most apical aspect of the defect to the apex of the socket x 100)

• Patients deemed eligible for immediate implant placement following extraction and intra-operative assessment by the attending supervisor.

• Patients that present with an oral-antral communication, post extraction.

• Patients that presents with the need for multiple, side by side extractions.

• Patients with coagulation disorders, on corticosteroids, uncontrolled diabetes mellitus, or any systemic disease where periodontal surgery is contraindicated and healing may be compromised.

• Pregnant and nursing women.

• Patients with any contact hypersensitivity to the related materials used in the study.

• Heavy tobacco users, >10 cigarettes per day.

• Patients unwilling to sign consent or follow the protocol of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Graduate Periodontic Clinic - University of Manitoba	Winnipeg	Manitoba	Canada	R3E 0W2

Sponsors and Collaborators

• University of Manitoba

Investigators

• Study Director: Anastasia Cholakis, DDS, University of Manitoba, Faculty of Graduate Studies, Periodontics

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 2, 2018

More Information

Publications

• Castro AB, Meschi N, Temmerman A, Pinto N, Lambrechts P, Teughels W, Quirynen M. Regenerative potential of leucocyte- and platelet-rich fibrin. Part B: sinus floor elevation, alveolar ridge preservation and implant therapy. A systematic review. J Clin Periodontol. 2017 Feb;44(2):225-234. doi: 10.1111/jcpe.12658. Epub 2017 Jan 10. Review.
• Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL, Dohan AJ, Mouhyi J, Dohan DM. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part IV: clinical effects on tissue healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Mar;101(3):e56-60.
• Fernández RF, Bucchi C, Navarro P, Beltrán V, Borie E. Bone grafts utilized in dentistry: an analysis of patients' preferences. BMC Med Ethics. 2015 Oct 20;16(1):71. doi: 10.1186/s12910-015-0044-6.
• Hauser F, Gaydarov N, Badoud I, Vazquez L, Bernard JP, Ammann P. Clinical and histological evaluation of postextraction platelet-rich fibrin socket filling: a prospective randomized controlled study. Implant Dent. 2013 Jun;22(3):295-303. doi: 10.1097/ID.0b013e3182906eb3.
• Iasella JM, Greenwell H, Miller RL, Hill M, Drisko C, Bohra AA, Scheetz JP. Ridge preservation with freeze-dried bone allograft and a collagen membrane compared to extraction alone for implant site development: a clinical and histologic study in humans. J Periodontol. 2003 Jul;74(7):990-9.
• MacBeth N, Trullenque-Eriksson A, Donos N, Mardas N. Hard and soft tissue changes following alveolar ridge preservation: a systematic review. Clin Oral Implants Res. 2017 Aug;28(8):982-1004. doi: 10.1111/clr.12911. Epub 2016 Jul 26. Review.
• Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study. Int J Periodontics Restorative Dent. 2003 Aug;23(4):313-23.
• Temmerman A, Vandessel J, Castro A, Jacobs R, Teughels W, Pinto N, Quirynen M. The use of leucocyte and platelet-rich fibrin in socket management and ridge preservation: a split-mouth, randomized, controlled clinical trial. J Clin Periodontol. 2016 Nov;43(11):990-999. doi: 10.1111/jcpe.12612. Epub 2016 Sep 21.
• Walker CJ, Prihoda TJ, Mealey BL, Lasho DJ, Noujeim M, Huynh-Ba G. Evaluation of Healing at Molar Extraction Sites With and Without Ridge Preservation: A Randomized Controlled Clinical Trial. J Periodontol. 2017 Mar;88(3):241-249. doi: 10.1902/jop.2016.160445. Epub 2016 Oct 27.

• Responsible Party: Dr. Jonathan Bouwer, Periodontal Resident, University of Manitoba
• ClinicalTrials.gov Identifier: NCT03331185
• Other Study ID Numbers: B2017:125
• First Posted: Nov 6, 2017
• Last Update Posted: Apr 30, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Dr. Jonathan Bouwer, Periodontal Resident, University of Manitoba: Extraction; Alveolar Ridge Augmentation; Freeze Dried Bone Allograft; Leukocytic Platelet Rich Fibrin; Volumetric Changes; Dense Polytetrafluoroethylene Membrane
• Additional relevant MeSH terms: Alveolar Bone Loss; Tooth Loss

Study Results

Participant Flow

Arm/Group Title	Freeze Dried Bone Allograft	L-PRF Clot
Arm/Group Description	Socket filled with Mineralized Cortical Freeze Dried Bone Allograft Freeze Dried Bone Allograft: Human derived bone particles used in oral and periodontal grafting procedures	Socket filled with L-PRF Clot L-PRF clot: L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.
Period Title: Overall Study
STARTED	14	12
COMPLETED	14	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Freeze Dried Bone Allograft	L-PRF Clot	Total
Arm/Group Description	Socket filled with Mineralized Cortical Freeze Dried Bone Allograft Freeze Dried Bone Allograft: Human derived bone particles used in oral and periodontal grafting procedures	Socket filled with L-PRF Clot L-PRF clot: L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.	Total of all reporting groups
Overall Participants	14	12	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.43 (12.92)	63.33 (14.66)	62.31 (13.5)
Sex: Female, Male (Count of Participants)
Female	5 35.7%	3 25%	8 30.8%
Male	9 64.3%	9 75%	18 69.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Canada	14 100%	12 100%	26 100%
Buccolingual Ridge Width measured 1mm from crest (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	11.38 (2.4)	11.28 (1.41)	11.3 (1.8)
Buccolingual Ridge Width measured 3mm from crest (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	11.82 (2.37)	12.20 (1.53)	12 (1.9)
Buccolingual Ridge Width measured 5mm from crest (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	12.17 (2.49)	12.47 (1.94)	12.3 (2.2)
Thickness of buccal plate measured at 1mm from crest (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	0.98 (0.5)	0.89 (0.3)	0.93 (0.4)
Thickness of buccal plate measured at 3mm from crest (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	1.08 (0.8)	1.31 (0.58)	1.19 (0.69)
Thickness of buccal plate measured at 5mm from crest (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	1.26 (0.98)	1.50 (0.64)	1.38 (0.8)
Buccolingual Keratinised Tissue Width (Millimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Millimeters]	15.25 (5.32)	16.4 (4.39)	15.8 (4.8)

Outcome Measures

1. Primary Outcome

Title	Overall Horizontal Change in Alveolar Ridge Width
Description	Calculated mean of post operative CBCT measurements of horizontal alveolar bone width changes following extraction and alveolar ridge preservation.
Time Frame	Difference reported on horizontal changes comparing CBCT analysis 11weeks after extraction and grafting compared to CBCT following extraction and grafting

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Freeze Dried Bone Allograft	L-PRF Clot
Arm/Group Description	Socket filled with Mineralized Cortical Freeze Dried Bone Allograft Freeze Dried Bone Allograft: Human derived bone particles used in oral and periodontal grafting procedures	Socket filled with L-PRF Clot L-PRF clot: L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.
Measure Participants	14	12
Mean (Standard Error) [Millimeters]	-1.34 (0.38)	-2.21 (0.41)

2. Secondary Outcome

Title	Buccolingual Change in Width of Keratinized Soft Tissue
Description	Difference in post operative measurement analysis of keratinized gingiva changes following extraction and alveolar ridge preservation
Time Frame	Soft tissue measurement at time of extraction and grafting and 12 weeks after extraction and grafting

Outcome Measure Data

Analysis Population Description

Only nine patients had implants placed within the exact specified 12 week timeframe from the date of extraction, therefore data collection and analysis were only performed on these participants.

Arm/Group Title	Freeze Dried Bone Allograft	L-PRF Clot
Arm/Group Description	Socket filled with Mineralized Cortical Freeze Dried Bone Allograft Freeze Dried Bone Allograft: Human derived bone particles used in oral and periodontal grafting procedures	Socket filled with L-PRF Clot L-PRF clot: L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.
Measure Participants	4	5
Mean (Standard Error) [Millimeters]	-1 (3.03)	-4 (2.7)

3. Secondary Outcome

Title	Post-operative Pain and Swelling
Description	Post-operative pain and complications measured by VAS-questionnaire obtained following extraction and grafting. The VAS-questionnaire contained the following categories to be answered 7days post-operatively: Pain, Swelling. A visual line scale of 100mm in length was provided with no pain/swelling on the one end and severe pain/swelling on the opposite end. Participants were instructed to rate their pain and swelling by marking a single line on the scale indicating the degree of pain/swelling they experienced. Markings were physically measured on the scale and converted into a score with 0 representing no pain/swelling and 1 representing severe pain/swelling.
Time Frame	Measured at 7 days following extraction and grafting

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Freeze Dried Bone Allograft	L-PRF Clot
Arm/Group Description	Socket filled with Mineralized Cortical Freeze Dried Bone Allograft Freeze Dried Bone Allograft: Human derived bone particles used in oral and periodontal grafting procedures	Socket filled with L-PRF Clot L-PRF clot: L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.
Measure Participants	14	12
Mean (Standard Deviation) [score on a scale]	0.22 (0.29)	0.23 (0.30)

Adverse Events

Time Frame	12weeks
Adverse Event Reporting Description	Patients were monitored 1-2weekly during the 12week healing period and any adverse events recorded by the treating clinician.
Arm/Group Title	Freeze Dried Bone Allograft		L-PRF Clot
Arm/Group Description	Socket filled with Mineralized Cortical Freeze Dried Bone Allograft Freeze Dried Bone Allograft: Human derived bone particles used in oral and periodontal grafting procedures		Socket filled with L-PRF Clot L-PRF clot: L-PRF is a second-generation platelet rich plasma obtained from autologous blood and contains several different growth factors, platelets and leucocytes in a complex fibrin matrix to accelerate the healing of soft and hard tissues.
All Cause Mortality
	Freeze Dried Bone Allograft		L-PRF Clot
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/12 (0%)
Serious Adverse Events
	Freeze Dried Bone Allograft		L-PRF Clot
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Freeze Dried Bone Allograft		L-PRF Clot
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/14 (50%)		3/12 (25%)
Surgical and medical procedures
Membrane loss earlier than 4weeks	7/14 (50%)		3/12 (25%)

Limitations/Caveats

Initial sample size calculation was 42, due to limited recruitment timeframe and period of study, a limited sample size was obtained.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.