Systemic Amoxicillin Plus Metronidazole in Peri-implantitis Treatment

Systemic Antibiotic Therapy (Amoxicillin Plus Metronidazole) as an Adjunct to Initial Non-surgical Treatment of Peri-implantitis; a Single Blind Randomized Controlled Study

The primary objective of this controlled clinical trial is to evaluate the clinical effect of systemic amoxicillin plus metronidazole therapy in conjunction with initial non-surgical treatment of peri-implantitis. The secondary objective is to assess the microbiological effectiveness of this peri-implantitis treatment approach.

The present study is a single-blind, randomized controlled clinical trial. Adult patients with at least one endosseous implant in the oral cavity with clinical and radiographical evidence of periimplantitis will be included in this study.

Patients with implants affected by peri-implantitis will receive initial periodontal treatment existing of oral hygiene instructions and mechanical cleansing of both implants and remaining dentition. Immediately after initial periodontal therapy patients will be instructed to rinse their mouth with 0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol twice daily during 30 seconds for 2 weeks. Additionally patients will receive a recipe for medication consisting of 500 mg amoxicillin and 500 mg metronidazole to be taken every 8 hours for the following 7 days or no recipe.

The main study parameter is the mean peri-implant bleeding score.

Study Overview

• Status: Completed
• Conditions: Periodontal Diseases; Peri-implantitis
• Intervention / Treatment: Drug: amoxicillin 500 mg + metronidazole 500 mg; Procedure: non-surgical periodontal and peri-implant treatment

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient is ≥ 18 years of age;
• The patient has at least one endosseous implant in the oral cavity with clinical and radiographical signs of peri-implantitis. Peri-implantitis is defined as a loss of marginal bone ≥ 2 mm as compared to the shoulder of the implant (the level at which the bone is normally located immediately after implant placement), in combination with bleeding and/or suppuration on probing and a peri-implant probing depth ≥ 5 mm;
• The implants have been in function for at least two years;
• The patient is capable of understanding and giving informed consent.

Exclusion Criteria:

• Medical and general contraindications for the surgical procedures;
• A history of local radiotherapy to the head and neck region;
• Pregnancy and lactation;
• Uncontrolled diabetes (HbA1c < 7% or < 53 mmol/mol)
• Mononucleosis infectiosa
• Organic neurological disorders
• Use of antibiotics during the last 3 months;
• Known allergy to amoxicillin, metronidazole or chlorhexidine;
• Long-term use of anti-inflammatory drugs;
• Full edentulism (no remaining teeth, only implants)
• Incapability of performing basal oral hygiene measures as a result of physical or mental disorders;
• Implants placed in areas augmented with autogenous bone from the crista iliac region;
• Implants placed in skin grafted areas;
• Implants with bone loss exceeding 2/3 of the length of the implant or implants with bone loss beyond the transverse openings in hollow implants;
• Implant mobility;
• Implants at which no position can be identified where proper probing measurements can be performed;
• Previous surgical treatment of the peri-implantitis lesions;
• Previous non-surgical treatment of the peri-implantitis lesions during the last 6 months (scaling or curettage)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antibiotics group; Patients will receive full-mouth mechanical cleansing of both implants and remaining dentition using ultrasonic instruments (EMS®) and hand instruments (scalers and curettes) in one or multiple sessions (max. 4). Prior to each session patients will rinse their mouth using 0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol during 30 seconds. At the final session all previously cleaned areas will be re-examined and cleaned. At the end of the final treatment session, the dental hygienist will give the patients an envelop containing a recipe for medication consisting of 500 mg amoxicillin and 500 mg metronidazole to be taken every 8 hours for the following 7 days plus a recipe for 500 ml mouthrinse (0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol, Perio-Aid®). After the final session patients will rinse their mouth using that mouthrinse twice daily during 30 seconds for 2 weeks.	Drug: amoxicillin 500 mg + metronidazole 500 mg; 500 mg amoxicillin and 500 mg metronidazole to be taken every 8 hours for 7 days; Procedure: non-surgical periodontal and peri-implant treatment; Patients are instructed on how to perform proper oral hygiene measures using an electric toothbrush, interdental brushes (to be used in combination with Corsodyl® gel) and floss (Oral-B® superfloss or Meridol® floss, at implants only). Patients will receive full-mouth mechanical cleansing of both implants and remaining dentition using ultrasonic instruments (EMS®) and hand instruments (scalers and curettes) in one or multiple sessions (max. 4). Prior to each session patients will rinse their mouth using 0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol during 30 seconds. At the final session all previously cleaned areas will be re-examined and cleaned.
Active Comparator: Control group; Patients will receive full-mouth mechanical cleansing of both implants and remaining dentition using ultrasonic instruments (EMS®) and hand instruments (scalers and curettes) in one or multiple sessions (max. 4). Prior to each session patients will rinse their mouth using 0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol during 30 seconds. At the final session all previously cleaned areas will be re-examined and cleaned. At the end of the final treatment session, the dental hygienist will give the patients an envelop containing a recipe for 500 ml mouthrinse (0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol, Perio-Aid®). After the final session patients will rinse their mouth using that mouthrinse twice daily during 30 seconds for 2 weeks.	Procedure: non-surgical periodontal and peri-implant treatment; Patients are instructed on how to perform proper oral hygiene measures using an electric toothbrush, interdental brushes (to be used in combination with Corsodyl® gel) and floss (Oral-B® superfloss or Meridol® floss, at implants only). Patients will receive full-mouth mechanical cleansing of both implants and remaining dentition using ultrasonic instruments (EMS®) and hand instruments (scalers and curettes) in one or multiple sessions (max. 4). Prior to each session patients will rinse their mouth using 0.12% chlorhexidine + 0.05% cetylpyridinium chloride without alcohol during 30 seconds. At the final session all previously cleaned areas will be re-examined and cleaned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline mean peri-implant bleeding score at 3 months	in percentages ranging from 0 (no change) to 100 (improvement)	3 months after therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline full-mouth periodontal bleeding score at 3 months	in percentages ranging from 0 (no change) to 100 (improvement)	3 months after therapy
change from baseline mean peri-implant and baseline full-mouth periodontal suppuration on probing score at 3 months	in percentages ranging from 0 (no change) to 100 (improvement)	3 months after therapy
change from baseline mean peri-implant and full-mouth periodontal probing pocket depth at 3 months	in millimeters ranging from 0 (no change) to high (improvement)	3 months after therapy
change from baseline mean peri-implant and full-mouth periodontal plaque score at 3 months	in percentages ranging from 0 (no change) to 100 (improvement)	3 months after therapy
change from baseline marginal soft tissue level at 3 months	in millimeters ranging from 0 (no change) to high (worsening)	3 months after therapy
change from baseline radiographic marginal peri-implant bone level at 3 months	in millimeters ranging from 0 (no change) to high (worsening)	3 months after therapy
change from baseline in detection frequency of 7 periodontal pathogens potentially residing in the peri-implant and periodontal area at 3 months		3 months after therapy
number of patients in need for additional surgery at teeth and implants		3 months after therapy
number of patients with implant failure, defined as implant mobility of previously clinically osseointegrated implants and removal of non-mobile implants because of progressive marginal bone loss or infection		3 months after therapy
number of patients with tooth loss, defined as removal of teeth because of progressive marginal bone loss or infection		3 months after therapy
number of patients with adverse events related to the treatment		3 months after therapy

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: October 26, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Periodontal Diseases; Peri-Implantitis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole; Amoxicillin
• Other Study ID Numbers: NL41441.042.12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No