Treatment of peri-implantitis with allografts and enamel proteins

ISRCTN	ISRCTN15000657
DOI	https://doi.org/10.1186/ISRCTN15000657
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	PS2023069
Sponsor	Arrow Development S.L.
Funder	Arrow Development S.L.

Submission date: 19/12/2023
Registration date: 21/12/2023
Last edited: 03/03/2025

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Oral Health

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Peri-implantitis is a condition that occurs in the tissues surrounding dental implants. It is characterized by inflammation of the connective tissue around the implant and loss of support bone. Allografts (transplanted tissues) have been described as a good option to reconstruct the bone defect related to peri-implantitis. Enamel matrix proteins have been previously described as an ideal material for periodontal regeneration alone or in combination with bone grafts. This study aims to measure the potential benefit of adding enamel matrix proteins to allografts in the reconstruction of bone defects due to peri-implantitis progression.

Who can participate?
Patients aged 18 years and over with implants for 1 year or more and diagnosed with advanced peri-implantitis

What does the study involve?
Participants will be randomly allocated to the test or control group during surgery. The control group will be treated with allografts alone. The test group will be treated with enamel matrix proteins and allografts. Sutures will be removed at 2 weeks after surgery. Clinical examinations will be performed at 4, 12, 24 and 48 weeks after surgery. Maintenance therapy will be carried out at 12, 24 and 48 weeks after therapy.

What are the possible benefits and risks of participating?
The benefit would be that participants' peri-implant disease will be treated and arrested. There is no additional risk of participating.

Where is the study run from?
Clínica Ortiz-Vigón (Spain)

When is the study starting and how long is it expected to run for?
September 2023 to August 2026

Who is funding the study?
Arrow Development SL (Spain)

Who is the main contact?
1. Erik Regidor, erik@ortizvigon.com
2. Alberto Ortiz-Vigón, alberto@ortizvigon.com

Contact information

Dr Alberto Ortiz-Vigón
Public, Scientific, Principal investigator

Alameda Urquijo nº 2 - 7ª planta
Bilbao
48008
Spain

ORCID ID	0000-0002-1863-5907
Phone	+34 (0)944 15 89 02
Email	alberto@ortizvigon.com

Dr Erik Regidor Correa
Scientific

Alameda Urquijo nº 2 - 7ª planta
Bilbao
48008
Spain

ORCID ID	0000-0003-3338-6379
Phone	+34 (0)944 15 89 02
Email	erik@ortizvigon.com

Study information

Primary study design	Interventional
Study design	Randomized clinical trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Influence of enamel matrix derivatives for the treatment of peri-implant-related osseous defects with minimal flap approach: a randomized clinical trial
Study objectives	The enamel matrix derivate simultaneous to intra-bony peri-implant related defect reconstruction with allogeneic bone graft has a better outcome in terms of radiographic defect fill and re-establishing peri-implant health when comparing with using only an allogeneic bone graft with minimally invasive surgical approaches.
Ethics approval(s)	Approved 19/12/2023, Basque Country local ethics committee (C/ Donostia-San Sebastián, nº 1. Vitoria-Gasteiz 01010, Vitoria, 01010, Spain; +34 (0)945 01 92 96; ceic.eeaa@euskadi.eus), ref: PS2023*
Health condition(s) or problem(s) studied	Peri-implantitis
Intervention	Study participants will be randomly allocated to the test or control group during surgery, just after completing implant decontamination procedures. The randomization sequence is determined using a block size of 4 with a 1:1 allocation. Allocation will be concealed through the use of sealed, opaque envelopes. Outcome assessors and patients will be blinded to group allocation. Surgical procedures will be performed 1 month after non-surgical periodontal treatment. On the same day of surgical therapy, an antibiotic will be administered for 7 days (amoxicillin 500 mg / 7 days / 8 hours). First, a minimally invasive surgical flap will be prepared over the implant neck. Large flaps will be avoided to minimize surgical post-operative complications such as dehiscence and loss of biomaterial. Control group: surgical reconstructive treatment of periimplantitis by means of implant surface decontamination with mechanical methods (Labrida BioClean Brush®), and osseous defect reconstruction by means of allogeneic bone graft (Straumann Allograft in particles). Test group: surgical reconstructive treatment of periimplantitis by means of implant surface decontamination with mechanical methods (Labrida BioClean Brush®), and osseous defect reconstruction by means of allogeneic bone graft (Straumann Allograft in particles) and adjunctive enamel matrix proteins (Straumann Emdogain®). Sutures will be removed 2 weeks after surgical therapy. Clinical examinations will be performed at 4,12,24 and 48 weeks after surgical therapy. Maintenance therapy will be realized at 12, 24 and 48 weeks after therapy.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Treatment success will be defined as the absence of bleeding on probing (BoP)/pus, probing pocket depth (PPD) ≤5 mm and ≤1 mm recession (measured using Periodontal Manual probe CP 15 Hu-Friedy) at 4, 12, 24 and 48 weeks after surgical therapy
Key secondary outcome measure(s)	Clinical assessments: One calibrated examiner will perform the assessments. The following variables will be assessed at four sites around the implant: plaque, probing pocket depth (PPD), bleeding on probing (BoP), probing attachment level (PAL) recession (REC). Keratinized mucosa (KM) will be measured in the buccal aspect of each included implant using Periodontal Manual probe CP 15 Hu-Friedy at baseline, 24 and 48 weeks. Surgical assessments: Defect configuration will be measured by one calibrated examiner in each clinical center to understand how much impact it has on clinical outcomes, measured using Periodontal Manual probe CP 15 Hu-Friedy intra-surgically. Osseous defect-related measures / recording of osseous defect characteristics: 1. Defect width (measured in mesial, distal, buccal, and palatal/lingual aspects) 2. Distance from implant neck to depth of the osseous defect (measured in mesial, distal, buccal, and palatal/lingual aspects) 3. Distance from osseous ridge to depth of the osseous defect (measured in mesial, distal, buccal, and palatal/lingual aspects) Radiographic assessments: Radiographic marginal bone level. Each included implant will be measured in mesial and distal aspects in mm with Image-J® digital software using intra-oral radiographs obtained before surgery (baseline) and at 6- and 12-month re-examinations. Analysis of radiographs will be performed by a specialist. The examiner will be blinded to treatment procedures. The assessment will include defect fill in both follow-up visits. Volumetric changes: Linear changes measured in Implant-Studio® digital software in 1, 3 and 5 mm from the mucosal peri-implant margin. Intra-oral scanning will be obtained before surgery (baseline) at 6 months and 12 months of re-examination. Analysis of STL archives will be performed by a specialist. The examiner will be blinded to treatment procedures. The assessment will include volumetric changes after matching the baseline intra-oral scanning, 6 months of intra-oral scanning and 12 months of intra-oral scanning.
Completion date	01/08/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	40
Key inclusion criteria	1. Age ≥18 years 2. Peri-implant bone defect ≥3 mm assessed radiographically 3. PPD ≥5 mm combined with bleeding on probing or suppuration 4. Intra-surgically, bone defect must have at least an intraosseous component of 3 mm and a width of no more than 4 mm 5. Implants ≥1 year in function
Key exclusion criteria	1. Treated for peri-implantitis during the previous 6 months 2. Intake of systemic or local antibiotics during the previous 6 months 3. Pregnant patients 4. Systemically unhealthy patients 5. Patients allergic to collagen
Date of first enrolment	01/01/2024
Date of final enrolment	26/02/2025

Locations

Countries of recruitment

Spain

Study participating centre

Clinica Ortiz-Vigón

Alameda Urquijo nº 2 - 7ª planta
Bilbao
48008
Spain

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available. All the information and documents will be saved in a secure database under a highly secure password and will be supervised by the study monitor.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file			19/12/2023	No	No

Additional files

44773_PROTOCOL.pdf: Protocol file

Editorial Notes

03/03/2025: The recruitment end date was changed from 01/02/2025 to 26/02/2025.
19/12/2023: Study's existence confirmed by the Basque Country local ethics committee.