E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Destructive inflammatory process affecting the soft and the hard tissues surrounding dental implants |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the present study is to evaluate the adjunctive effect of systemically administered antibiotics during surgical treatment of peri-implantitis. |
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E.2.2 | Secondary objectives of the trial |
1. Evaluate changes in the clinical and radiographic outcome after surgical intervention of peri-implantitis.
2. Assess the development of antibiotic resistance in the oral and intestinal microflora after treatment with systemically administered antibiotics.
3. Compare quantitative and qualitative changes in the oral and intestinal microflora after two different combinations of antibiotic treatment (penicillin-V+metronidazol versus amoxicillin+metronidazol).
4. Determine antibiotic concentration in saliva and feces.
5. Evaluate the safety of antimicrobial treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ≥18 year
2. Patients who has been referred by a general dentist to a specialist clinic in periodontology for treatment of peri-implantitis.
3. Having sign of peri-implantitis around at least one osseointegrated dental implant that has been in function for ≥ one year
4. Peri-implantitis is diagnosed when; PPD of ≥ 6mm can be found at a dental implant in association with BOP and/or suppuration together with the loss of marginal alveolar bone of more than 2 mm detected on intraoral radiographs (giving radiographic exposure of at least ≥ 3 fixture threads).
5. Partially or completely edentulous subjects with healthy or treated periodontal conditions enrolled in a regular supportive program.
6. Full-Mouth Plaque Score (FMPS) ≤ 30
7. Signed informed consent
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E.4 | Principal exclusion criteria |
1. Known allergy to amoxicillin, penicillin (PcV), metronidazole or betalactam.
2. Contraindication for dental surgical treatment (i.e. immunocompromised, uncontrolled DM (B-GHb-A1C 8–9 %, 64–75 mmol/mol), I.V bisphosphonate treatment due to malignancy, pregnant and lactating women).
3. Incapability to perform basal oral hygiene measures due to physical or mental disorders.
4. Received systemic antimicrobial therapy in the past three months.
5. Currently on allopurinol, digoxin, disulfirom, lithium, busulfan, 5-fluorouracil, methotrexate, phenytoin, cyclosporine and warfrin.
6. Known severe chronic peripheral or central disease of the nervous system
7. Known alcohol abuse
8. Known hepatic encephalopathy
9. Known lactose intolerance, galactose intolerance
10. Untreated periodontal condition.
11. Implant showing sign of mobility.
12. Implants with bone loss exceeding 2/3 of the length of the implant or implants with bone loss beyond any transverse openings in hollow implants.
13. Any medical condition or on any concomitant medication that, in the opinion of the investigator, might interfere with the evaluation of the study objectives or jeopardize patient safety
Patients with xerostomia or having slow bowel motion will be excluded from the group of patients providing salivary and fecal samples.
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E.5 End points |
E.5.1 | Primary end point(s) |
Peri-implant pocket depth reduction/Probing pocket depth (PPD) reduction |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, 6 months and 12 month |
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E.5.2 | Secondary end point(s) |
1. Marginal bone level stability measured directly postoperative and 12 month after treatment
2. Reduction of clinical soft tissue inflammation, bleeding on probing (BOP).
3. Soft tissue recession (REC) and clinical attachment level gain (CAL)
4. Quantitative and qualitative change in levels of the peri-implant periopathogenic microflora
5. Susceptibility changes of the oral and intestinal microflora to amoxicillin, metronidazole and penicillin.
6. Quantitative and qualitative changes in the oral and intestinal microflora.
7. Concentration of amoxicillin, metronidazole and PcV in saliva and feces.
8. Follow-up of adverse events related or unrelated to the investigated medical products
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measured directly postoperative and 12 month after surgery |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |