Trial Outcomes & Findings for Comparison of Amnion Chorion Membrane vs. Dense Polytetrafluoroethylene Membrane in Ridge Preservation Procedures (NCT NCT02602223)

Results Overview

A radiographic stent will be fabricated with reproducible access holes ≈5 mm apical to the mid-facial and mid-lingual gingival margin of the teeth to be extracted. On day of surgery, a calibrated examiner masked to treatment allocation, will record initial clinical bucco-lingual (iCBL) ridge measurements in millimeters (mm), through the access holes in the stent, using calipers. Approximately 3.5(±0.5)-months post extractions, the calibrated examiner masked to treatment allocation, will record the final clinical bucco-lingual (fCBL) ridge measurements in mm using the calipers as described earlier. The difference between fCBL and iCBL will be calculated as change in clinical horizontal ridge width dimensions in mm (cΔHD).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

3-4 months

Results posted on

2016-10-07

Participant Flow

Screening, recruitment and study-related procedures were done at Indiana University School of Dentistry (IUSD) clinics between 9/17/2012 and 7/14/2014

Participant milestones

Participant milestones
Measure	Amnion Chorion Membrane & d-PTFE Amnion chorion membrane or d-PTFE will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane or d-PTFE over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM or d-PTFE (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed.
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Amnion Chorion Membrane vs. Dense Polytetrafluoroethylene Membrane in Ridge Preservation Procedures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amnion Chorion Membrane & d-PTFE n=9 Participants Amnion chorion membrane or d-PTFE will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane or d-PTFE over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM or d-PTFE (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=93 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants
Age, Continuous	54.88 Years n=93 Participants
Sex: Female, Male Female	3 Participants n=93 Participants
Sex: Female, Male Male	6 Participants n=93 Participants
Region of Enrollment United States	9 participants n=93 Participants
Total Number of sites (maxilla vs Mandible) Total	22 Sites n=93 Participants
Total Number of sites (maxilla vs Mandible) Maxilla	14 Sites n=93 Participants
Total Number of sites (maxilla vs Mandible) Mandible	8 Sites n=93 Participants
Number of participants with multiple study sites Single paired study sites	7 participants n=93 Participants
Number of participants with multiple study sites Multiple (two) paired study sites	2 participants n=93 Participants

PRIMARY outcome

Timeframe: 3-4 months

Population: change in clinical horizontal ridge width dimensions in mm - cΔHD

A radiographic stent will be fabricated with reproducible access holes ≈5 mm apical to the mid-facial and mid-lingual gingival margin of the teeth to be extracted. On day of surgery, a calibrated examiner masked to treatment allocation, will record initial clinical bucco-lingual (iCBL) ridge measurements in millimeters (mm), through the access holes in the stent, using calipers. Approximately 3.5(±0.5)-months post extractions, the calibrated examiner masked to treatment allocation, will record the final clinical bucco-lingual (fCBL) ridge measurements in mm using the calipers as described earlier. The difference between fCBL and iCBL will be calculated as change in clinical horizontal ridge width dimensions in mm (cΔHD).

Outcome measures

Outcome measures
Measure	Amnion Chorion Membrane n=11 Sites Amnion chorion membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed	d-PTFE Membrane n=11 Sites dense polytetrafluoroethylene membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the Experimental side Placing d-PTFE membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol d-PTFE membranes (Cytoplast, Osteogenics Medical, Texas, U.S.A) were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed
Amount of Preservation of Alveolar Ridge Dimensions i.e..,Clinical Horizontal Ridge Width Change in Millimeter as Result of Ridge Preservation Procedures	2.54 millimeters Standard Deviation 1.29	2.72 millimeters Standard Deviation 1.01

PRIMARY outcome

Timeframe: 3-4 month

Population: The micro-architectural variable; bone volume density (BV/TV),was quantified and is reported as percentages.

Approximately 3-months post extractions, a 2.5x10mm core of bone will be removed from the center of the residual ridge using a 2.5mm inner-diameter trephine bur. Cores will be immediately placed into 10%-formalin. A high-resolution microtomographic scanner will be used and images will be scanned at a voxel size of 8µm3. Moist bone cores will be wrapped in paraffin and scanned in air. Cores will be rotated in 0.7 degree increments with 450milli second time exposition. A 0.5m aluminum filter will be used to remove image noise. After scanning, 3D microstructural image data will be reconstructed using software. Structural indices will be calculated using a software. The micro-architectural variables; bone volume density (BV/TV), and bone surface density (BS/BV); will be quantified and reported as percentages.

Outcome measures

Outcome measures
Measure	Amnion Chorion Membrane n=9 Participants Amnion chorion membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed	d-PTFE Membrane n=9 Participants dense polytetrafluoroethylene membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the Experimental side Placing d-PTFE membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol d-PTFE membranes (Cytoplast, Osteogenics Medical, Texas, U.S.A) were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed
Evaluation of Preservation of Ridge Quality Through Microtomographic Analysis for Microarchitectural Parameters Expressed as Percentages.	51.74 Percentage of BV/TV Standard Deviation 17.13	37.31 Percentage of BV/TV Standard Deviation 11.93

PRIMARY outcome

Timeframe: 3-4 months

Population: New bone/osteoid Percentages

Approximately 3.5(±0.5)-months post extractions, a 2.5x10mm core of bone will be removed from the center of the residual ridge using a 2.5mm inner-diameter trephine bur. Cores will be immediately placed into 10%-formalin. Cores will be process and embedded in polymethylmethacrylate and sectioned to 5μm thickness and sections will be stained with Goldener's Trichrome. With the Goldener's trichrome, mineralized bone appears as green or blue regions, osteoid appears orange-red, nuclei appears blue-grey and graft remnants appear grey. Additional differentiation between graft and new bone will be achieved by morphologically assessing each sample individually. A slide scanner will be used to image the sample (20x magnification), and a software program will be used for the histomorphometric analysis, to quantify the amount of total mineralized bone, new bone / osteoid, soft tissue, and residual graft remnants in percentages .

Outcome measures

Outcome measures
Measure	Amnion Chorion Membrane n=9 Participants Amnion chorion membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed	d-PTFE Membrane n=9 Participants dense polytetrafluoroethylene membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the Experimental side Placing d-PTFE membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol d-PTFE membranes (Cytoplast, Osteogenics Medical, Texas, U.S.A) were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed
Evaluation of Preservation of Ridge Quality Through Histological Analysis for Microarchitectural Parameters Expressed as Percentages.	8.31 Percentage of New bone Standard Deviation 8.20	3.50 Percentage of New bone Standard Deviation 3.59

PRIMARY outcome

Timeframe: 0-2 weeks

Population: VAS score at 24 hours post operative

A visual Analog score (VAS) pain scale form (scale of 1 to 10) will be provided with instructions to record pain levels on both surgical sites every day for 2-weeks post-surgery. VAS score of 10 indicates highest level of pain and 0 indicates no pain. Subjects will also asked to log any pain medications taken in that 2-week period. Subjects will be seen at 1\&2 weeks for post-operative evaluation and VAS forms will be collected. Data will be reported as Average VAS score.

Outcome measures

Outcome measures
Measure	Amnion Chorion Membrane n=9 Participants Amnion chorion membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed	d-PTFE Membrane n=9 Participants dense polytetrafluoroethylene membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the Experimental side Placing d-PTFE membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol d-PTFE membranes (Cytoplast, Osteogenics Medical, Texas, U.S.A) were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed
Post Operative Pain	1.82 Units on a scale of 10 Standard Deviation 1.57	4.09 Units on a scale of 10 Standard Deviation 2.7

PRIMARY outcome

Timeframe: 3-4 months

Population: Change in horizontal ridge width (RΔHD).

Radiographic stent with radiopaque reference plane (RRP) will be used to obtain pre-extraction CBCT scans. Approximately 3-months post extractions, a second CBCT will be taken. Radiographic Analyses will be done using radiographic image analysis software by a calibrated examiner. The initial relative crest (iRC) reference point will be determined. The buccal and lingual crests at the central plane of site will be marked and distances from this crest to RRP will be measured in mm. The average distance of the buccal crest height and the lingual crest height will be calculated and that value will be used to determine the iRC for that site. Initial Bucco-lingual (iRBL) measurements will be recorded at 1 mm, 3 mm and 7 mm from iRC in all five planes. The final bucco-lingual (fRBL) measurements will be recorded on the second CBCT, using the same method as described before and using the iRC reference. Differences between iRBL and the fRBL reflect change in horizontal ridge width (RΔHD).

Outcome measures

Outcome measures
Measure	Amnion Chorion Membrane n=9 Participants Amnion chorion membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed	d-PTFE Membrane n=9 Participants dense polytetrafluoroethylene membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the Experimental side Placing d-PTFE membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol d-PTFE membranes (Cytoplast, Osteogenics Medical, Texas, U.S.A) were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed
Amount of Preservation of Alveolar Ridge Dimensions Following Ridge Preservation Procedures i.e., Horizontal Ridge Width Height Change in Millimeters as Assessed Through Analysis of CBCT Scans.	1.33 millimeters Standard Deviation 0.72	2.53 millimeters Standard Deviation 3.34

PRIMARY outcome

Timeframe: 3-4 months

Population: Change in vertical dimension at each plane (RΔVD) i.e., iRC - nRC = (RΔVD). Positive (RΔVD) values indicate relative loss of crestal bone height and negative (RΔVD) values indicate relative gain of crestal bone height.

Radiographic stent with a radiopaque reference plane (RRP) will be used to obtain pre-extraction CBCT scans. Approximately 3.5(±0.5)-months post extractions, a second CBCT will be taken. Radiographic Analyses will be done using radiographic image analysis software by a calibrated examiner. Initial relative crest iRC will be determined as described above from the initial CBCT. In the second CBCT, vertical distance from the iRC from initial CBCT will be used to recreate the iRC. New relative crest will be determined for each of the three planes (nRC) as above. The difference between iRC and nRC indicates change in vertical dimension at each plane (RΔVD) i.e., iRC - nRC = (RΔVD). Positive (RΔVD) values indicate relative loss of crestal bone height and negative (RΔVD) values indicate relative gain of crestal bone height.

Outcome measures

Outcome measures
Measure	Amnion Chorion Membrane n=9 Participants Amnion chorion membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the active comparator. Placing Amnion chorion membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol ACM (BioXclude, Snoasis Medical, Colorado, U.S.A were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed	d-PTFE Membrane n=9 Participants dense polytetrafluoroethylene membrane will be placed over bone graft after socket preservation on randomly assigned side of the mouth i.e., contra-lateral to the Experimental side Placing d-PTFE membrane over grafted site: Selected teeth were extracted with minimal trauma to hard and soft tissues. The extraction sites were evaluated to verify presence of intact socket walls. Sockets were thoroughly debrided and a combination of demineralized freeze-dried bone and mineralized freeze-dried bone allograft from a single lot number (Maxxeus, Ohio, U.S.A) was placed in the sockets. Per randomization protocol d-PTFE membranes (Cytoplast, Osteogenics Medical, Texas, U.S.A) were tucked into the buccal and lingual flaps, which were minimally elevated (2-3mm) and d-PTFE sutures (Osteogenics Medical, Texas, U.S.A) were used to keep membrane in place. Primary closure was not attempted and membranes were intentionally left exposed
Amount of Preservation of Alveolar Ridge Dimensions Following Ridge Preservation Procedures i.e., Vertical Ridge Height Change in Millimeters as Assessed Through Analysis of CBCT Scans.	-0.24 millimeters Standard Deviation 0.91	1.18 millimeters Standard Deviation 2.22

Adverse Events

Amnion Chorion Membrane

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

d-PTFE Membrane

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Sivaraman Prakasam

Oregon Health & Sciences University

Phone: 503-346-4711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place