A survey of endpoint characteristics in periodontal clinical trials published 1988-1992, and implications for future studies.
Hujoel P P,DeRouen T A
Journal of clinical periodontology
Endpoints are conditions or events that are associated with individual study subjects and that are used to assess treatment efficacy. 2 types of endpoints can be distinguished: "true" endpoints (reflect unequivocal evidence of tangible benefit to the patient) and "surrogate" endpoints (usually a measure of disease process). The purpose of this study was to survey four aspects of endpoint usage in randomized controlled trials (RCT's) on the treatment of periodontitis: (1) the typical number of endpoints per RCT, (2) the proportion of RCTs using the same endpoint, (3) the proportion of RCTs using true endpoints, and (4) whether treatment choice influenced endpoint choice. 92 publications (1988-1992) reporting on 82 RCT's were identified. The typical number of endpoints per RCT was 6 (range: 1-28). The 3 most frequently used endpoints were mean probing depth (78% of the trials), mean probing attachment level (66%), and the plaque index (37%). In total, 153 distinct surrogate endpoints were defined. Most of these were used infrequently; over 80% of the 153 endpoints were used in fewer than 5 of the 82 trials. No trials used tooth loss as a true endpoint. In the design of an RCT, treatment choice influenced surrogate endpoint choice. Surrogate endpoints based on re-entry surgery were exclusively used for regenerative procedures and microbiological surrogate endpoints were mostly used for RCT's on anti-microbials. The conclusion is that the typical RCT used multiple surrogate endpoints, some of which were used infrequently by other trials. Such endpoint usage characteristics are suitable for exploratory RCTs (designed to identify active treatments or to elucidate treatment mechanisms). The question is raised as to whether periodontal research has reached the point of needing properly designed definitive studies, whose purpose it would be to provide unequivocal evidence of tangible benefits to the patient by the various treatments. If a need for definitive randomized controlled trials is perceived, then the use of (multiple) surrogate endpoints as primary outcomes should be questioned. Surrogate endpoint usage has led to both false positive and false negative conclusions in other chronic disease studies. Endpoint selection and validation in RCTs may be an important element in resolving controversies about periodontal treatments.
Omega-3 PUFA and aspirin as adjuncts to periodontal debridement in patients with periodontitis and type 2 diabetes mellitus: Randomized clinical trial.
Castro Dos Santos Nidia C,Andere Naira M R B,Araujo Cássia F,de Marco Andrea C,Kantarci Alpdogan,Van Dyke Thomas E,Santamaria Mauro P
Journal of periodontology
BACKGROUND:Supplementation with omega-3 polyunsaturated fatty acids (ω-3 PUFA) and low-dose aspirin (ASA) have been proposed as a host modulation regimen to control chronic inflammatory diseases. The aim of this study was to investigate the clinical and immunological impact of orally administered ω-3 PUFA and ASA as adjuncts to periodontal debridement for the treatment of periodontitis in patients type 2 diabetes. METHODS:Seventy-five patients (n = 25/group) were randomly assigned to receive placebo and periodontal debridement (CG), ω-3 PUFA + ASA (3 g of fish oil/d + 100 mg ASA/d for 2 months) after periodontal debridement (test group [TG]1), or ω-3 PUFA + ASA (3 g of fish oil/d + 100 mg ASA/d for 2 months) before periodontal debridement (TG2). Periodontal parameters and GCF were collected at baseline (t0), 3 months after periodontal debridement and ω-3 PUFA + ASA or placebo for TG1 and CG (t1), after ω-3 PUFA + ASA (before periodontal debridement) for TG2 (t1), and 6 months after periodontal debridement (all groups) (t2). GCF was analyzed for cytokine levels by multiplex ELISA. RESULTS:Ten patients (40%) in TG1 and nine patients (36%) in TG2 achieved the clinical endpoint for treatment (less than or equal to four sites with probing depth ≥ 5 mm), as opposed to four (16%) in CG. There was clinical attachment gain in moderate and deep pockets for TG1. IFN-γ and interleukin (IL)-8 levels decreased over time for both test groups. IL-6 levels were lower for TG1. HbA1c levels reduced for TG1. CONCLUSION:Adjunctive ω-3 and ASA after periodontal debridement provides clinical and immunological benefits to the treatment of periodontitis in patients with type 2 diabetes.
Different antibiotic protocols in the treatment of severe chronic periodontitis: A 1-year randomized trial.
Borges Ivan,Faveri Marcelo,Figueiredo Luciene Cristina,Duarte Poliana Mendes,Retamal-Valdes Belén,Montenegro Sheyla Christinne Lira,Feres Magda
Journal of clinical periodontology
AIM:To evaluate the clinical effects of different dosages of metronidazole (MTZ) and durations of MTZ + amoxicillin (AMX) in the treatment of generalized chronic periodontitis (GChP). MATERIAL AND METHODS:Subjects with severe GChP were randomly assigned to receive scaling and root planing (SRP)-only, or combined with 250 or 400 mg of MTZ + AMX (500 mg) thrice a day (TID), for 7 or 14 days. Subjects were monitored for 1 year. RESULTS:One hundred and nine subjects were enrolled. At 1 year, 61.9% and 63.6% of the subjects receiving AMX + 250 or 400 mg of MTZ for 14 days, respectively, reached the clinical endpoint for treatment (≤4 sites with probing depth ≥5 mm), against 31.8% of those taking 250 or 400 mg of MTZ for 7 days (p < .05) and 13.6% of those receiving SRP-only (p < .05). Fourteen days of MTZ + AMX was the only significant predictor of subjects reaching the clinical endpoint at 1 year (OR, 5.26; 95% CI, 2.3-12.1, p = .0000). The frequency of adverse events did not differ among treatment groups (p > .05). CONCLUSION:The adjunctive use of 400 or 250 mg of MTZ plus 500 mg of AMX/TID/14 days offers statistically significant and clinically relevant benefits over those achieved with SRP alone in the treatment of severe GChP. The added benefits of the 7-days regimen in this population were less evident. (ClinicalTrials.gov NCT02735395).
One-Stage Full Mouth Instrumentation (OSFMI): Clinical Outcomes of an Innovative Protocol for the Treatment of Severe Periodontitis.
Mensi Magda,Feres Magda,Calza Stefano,Sordillo Annamaria,Scotti Eleonora,Garzetti Gianluca
Journal of the International Academy of Periodontology
AIMS:This case series study aimed to assess the clinical outcomes of a novel protocol for the treatment of patients with severe periodontitis. MATERIALS AND METHODS:Twenty (20) patients with severe periodontitis underwent a single session of One-Stage Full-Mouth Instrumentation (OSFMI) involving supra- and sub-gingival air-polishing with erythritol and chlorhexidine powder and ultrasonic root surface debridement and calculus removal, in association with systemic amoxicillin and metronidazole. Pocket Probing Depth (PPD), Clinical Attachment Level (CAL), Recession (REC), Bleeding on Probing (BOP) and Plaque Index (PI) were collected at baseline (T0), 6 weeks (T1), 3 months (T2) and 6 months (T3). RESULTS:At 6 months, 30% of subjects reached the primary clinical endpoint (less than or equal to4 sites with PD greater than or equal to 5 mm). The percentage of BOP decreased from 49.08 (CI95% 36.06; 62.1) at T0 to 12.97 (CI95% 7.57; 18.37) at T3. The mean number pockets with PPD≥ 5 mm and PPD greater than or equal to 7 mm decreased significantly, from 46.0 and 20.6 at T0 to 11.5 and 2.8 at T3 respectively (p less than 0.001). CONCLUSION:The OSFMI protocol led to clinical results comparable to those obtained with traditional SRP. Researchers are encouraged to test this protocol in randomized clinical trials with longer periods of observation.
Proposal of a Clinical Endpoint for Periodontal Trials: The Treat-to-Target Approach.
Feres Magda,Retamal-Valdes Belen,Faveri Marcelo,Duarte Poliana,Shibli Jamil,Soares Geisla Mary Silva,Miranda Tamires,Teles Flavia,Goodson Max,Hasturk Hatice,Van Dyke Thomas,Ehmke Benjamin,Eickholz Peter,Schlagenhauf Ulrich,Meyle Joerg,Koch Raphael,Kocher Thomas,Hoffmann Thomas,Kim Ti-Sun,Kaner Dogan,Figueiredo Luciene Cristina,Doyle Helio
Journal of the International Academy of Periodontology
OBJECTIVE:The selection of proper outcome measures is a critical step in clinical research. Most randomized clinical trials (RCTs) assessing the effects of initial anti-infective periodontal therapies use surrogate outcomes as primary outcome variables, such as mean changes in probing depth (PD) or in clinical attachment. However, these parameters do not reflect disease remission/control at patient level, which has led to subjective interpretations of the data from RCTs and Systematic Reviews. Based on a comprehensive analysis of 724 patients from USA, Germany and Brazil treated for periodontitis, this paper suggests that the clinical endpoint of "≤4 sites with PD≥5mm" is effective in determining disease remission/control after active periodontal treatment and therefore, may represent a pertinent endpoint for applying the treat-to-target concept in RCTs. Furthermore, regression models showed that the presence of >10% and >20% sites with bleeding on probing in the mouth post-treatment increases the risk of a patient leaving the endpoint from 1-2 years (OR=3.5 and 8.7, respectively). Researchers are encouraged to present results on this outcome when reporting their trials, as this will allow for an objective comparison across studies and facilitate systematic reviews, and consequently, the extrapolation of data from research to clinical practice.
Effects of a full-mouth disinfection protocol on the treatment of type-2 diabetic and non-diabetic subjects with mild-to-moderate periodontitis: one-year clinical outcomes.
Almeida Mariana Linhares,Duarte Poliana Mendes,Figueira Eduardo Aleixo,Lemos Janaína Cavalcante,Nobre Cintia Mirela Guimarães,Miranda Tamires Szeremeske,de Vasconcelos Gurgel Bruno César
Clinical oral investigations
OBJECTIVES:This study compared the clinical effects of a full-mouth disinfection (FMD) protocol for the treatment of mild-to-moderate periodontitis in type 2 diabetic and non-diabetic subjects for up to 1 year. Secondary aim was to evaluate the effects of this therapy on the salivary levels of periodontal pathogens between diabetics and non-diabetics. MATERIAL AND METHODS:Twenty-six type 2 diabetic subjects and 28 non-diabetic subjects with mild-to-moderate periodontitis received full-mouth scaling and root planing within 24 h, application of chlorhexidine digluconate (CHX) gel in pockets and tongue plus CHX rinses for 14 days. Clinical monitoring was performed at baseline, 3, 6, and 12 months post-therapy. Salivary levels of red complex bacterial species were evaluated at baseline, 6, and 12 months post-therapy by qPCR. RESULTS:Intention-to-treat analyses were performed for seven diabetics and three non-diabetics that did not return for the 12-month evaluation. Most clinical parameters improved significantly at 3, 6, and 12 months post-therapies for both groups (p < 0.05). Overall, there were no significant differences in clinical parameters between groups after therapy (p > 0.05). At 1 year, 39.3% and 50.0% of the non-diabetic and diabetic subjects, respectively, achieved the desired clinical endpoint for treatment (≤ 4 sites with probing depth ≥ 5 mm) (primary outcome variable) (p > 0.05). FMD did not promote changes in the salivary levels of pathogens in either of the groups (p > 0.05). Levels of T. forsythia were lower in diabetic than in non-diabetic subjects at 6 months post-therapy (p < 0.05). CONCLUSIONS:Type 2 diabetic subjects and systemically healthy subjects with mild-to-moderate periodontitis responded similarly to the proposed FMD protocol for up to 1 year. CLINICAL RELEVANCE:There is a general thought that diabetics do not answer as well as non-diabetics to periodontal treatments. However, this study showed that diabetics and non-diabetics respond equally to the FMD protocol. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02643771.