A Study to Treat Patients With Edentulous Mandibles With Two Straumann 3.3mm Diameter Bone Level Implants

Study Overview
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Brief Summary
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The purpose of this study is to assess the change of crestal bone level at the Titanium Zirconium (TiZr) compared to Titanium (grade IV) implant between surgery and 6, 12, 24, and 36 month post surgery.

Detailed Description
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This is a clinical trial to compare crestal bone level changes, soft tissue parameters, implant success and survival between small diameter implants in edentulous mandibles restored with removable overdentures. An initial patient evaluation will be conducted to determine wether a patient meets the study inclusion and exclusion criteria. The edentulous subjects will undergo surgery for placement of two dental implants, the test and control implant. The implants will be placed in the intraforaminal region. A gingival former will be inserted in the implant after implant placement to ensures a transmucosal healing. After 6 to 8 weeks the healing abutments will be retrieved and the locator abutments will be connected to the implant. The removable prosthesis will be prepared and connected to the implants two weeks later. The study will be blinded until 12 month post surgery and completed with an unblinded follow up period up to 3 years. Straumann will deliver the randomization envelopes to the sites which had been created by an independent Clinical Research Organization (CRO). The randomization envelopes are marked with a sequential number. The master randomization list will be kept at Straumann. The success and survival of the implants, soft tissue conditions, success of the prosthesis part and product safety will be assessed after 6, 12, 24, and 36 month after surgery. Source data verification will be performed by qualified study monitors to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources. Data will be recorded on standardized Case Report Forms for all study subjects from whom informed consent is obtained. The investigator will be responsible for the accuracy of the data entered on the Case Report Forms. All source documents pertaining to this study will be maintained by the investigator and made available for inspection by authorized persons. Sample size calculations are proceeded for a given range of clinical relevant differences between test and control implant and a given range of standard deviations with the two sided paired t-test under a significance level of 0.05 and with a power of 80 percent. To be robust against deviations from the assumption of normality and to take into account possible dropouts it is good clinical practice to increase the calculated sample size by about 10 to 20 percent. To detect a clinical relevant difference down to 0.1 with a standard deviation of 0.3, one needs 73 plus 15 (88) patients for the study. Management of dropouts and missing data will depend on their frequency and the particular outcome measure. Any such adjustments will be described completely. All data will be included in the analysis. If outliers are determined to exist, an additional analysis excluding such outliers may be performed and the rationale for such exclusion will be described completely. A first data analysis including data up to 12 month after surgery is planned after all patients have completed the respective study period. Inferential statistical analysis at this stage will be restricted to the primary efficacy parameter. The final data analysis will be performed after all patients have completed the study. Categorical data will be described as contingency tables with frequencies and percentage, whereby the dominator for percentages is defined as the number of patients in the respective analysis set. Continuous data will be summarised by mean, standard deviation, minimum, 1st quartile, median, 3rd quartile and maximum. Also the number of missing and nonmissing values will be given. Tables will be presented by device type and or total, as appropriate. Preabutment connection values will serve as baseline values. Hypothesis tests will be carried out at a two sided significance level of 5 percent, except for the primary efficacy analysis. The confirmatory noninferiority test will be performed at a one sided 2.5 percent significance level. As usual for secondary, no adjustment os significance level for multiple testing will be performed. In case of unacceptable deviations from the statistical model assumption, transformations of the data, the use of different distributional models or nonparametric approaches will be considered. All statistical calculations and analyses will be performed using the Statistical Analysis System (SAS) version 9.1.13 or higher.

Official Title
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A Randomized, Controlled, Double Blind, Clinical Trial to Treat Patients With Edentulous Mandibles With Two Straumann 3.3mm Ø Bone Level Implants by Comparing Two Different Implant Alloys in Split Mouth Design.

Conditions
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Jaw, Edentulous

Intervention / Treatment
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* Device: Titanium Zircon implant
* Device: Titanium Grade IV implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have voluntarily signed the informed consent form Males and females must be 18 years of age. Patients must present with an edentulous mandible at the time of surgery. The last tooth or teeth in the mandible must have been extracted or lost more than 8 weeks before the date of first stage surgery. The opposing dentition must be edentulous with a denture (implant borne or conventional) or natural or restored teeth Adequate bone height of at least 9 mm above vital structures (because the minimal available implant lengths is 8mm) in the intraforaminal region. Available bone width should be in such way that 3.3 mm implants can be placed without the use of concurrent bone augmentation techniques. Harvested bone from the drilling sites may be used to cover minor dehiscence defects. Patients must be committed to participate in the study for three years of follow-up examinations Exclusion Criteria: Medical conditions requiring prolonged use of steroids History of leukocyte dysfunction and deficiencies Patients with sever hemophilia History of head and neck radiation or chemotherapy Patients with history of renal failure The application of bisphosphonate medication History of uncontrolled endocrine disorders Physical handicaps that would interfere with the ability to perform adequate oral hygiene Use of any investigational drug or device within the 30-day period immediately prior to implant surgery on study day 0. Alcoholism or drug abuse Patients with known infection of HIV Patients who smoke more than 10 cigarettes per day or cigar equivalents, or who chew tobacco (not greater than 10 cigarette equivalents) Fertile females with no adequate method of birth control (contraceptive pill, barrier method, etc.) Conditions or circumstances, in the opinion of the investigator, which would prevent completion of study participation or interfere with analysis of study results, such as history of non-compliance, unreliability.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Titanium Zircon implant<br>Intervention: each subject will receive two Straumann bone level implants, one implant is fabricated with Titanium Zircon and the other is a grade IV Titanium implant. Both implants will be randomly placed in the interforaminal region of the edentulous mandible, one on the right half and the other in the left part. Both implants will be treated the same way. | Device: Titanium Grade IV implant<br>* The implant surgery is performed under local anesthesia following standard surgical techniques. The surgeon will be supported by one or two assistants. The bone will be excavated and prepared for the placement of the implant. After the implant was placed by using a hand ratched or motor drive device, a healing abutment will be inserted to ensure a transmucosal healing.<br>|
| Placebo Comparator: Titanium Grade IV implant<br>Intervention: each subject will receive two Straumann bone level implants, one implant is fabricated with Titanium Zircon and the other is a grade IV Titanium implant. Both implants will be randomly placed in the interforaminal region of the edentulous mandible, one on the right half and the other in the left part. Both implants will be treated the same way. | Device: Titanium Zircon implant<br>* The implant surgery is performed under local anesthesia following standard surgical techniques. The surgeon will be supported by one or two assistants. The bone will be excavated and prepared for the placement of the implant. After the implant was placed by using a hand ratched or motor drive device, a healing abutment will be inserted to ensure a transmucosal healing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Crestal Bone Level Between Surgery and 12 Months, to Compare Between the Titan Zircon Implant and the Titan Grade IV Implant. | Panoramic radiographs with standardized setting were taken at the implant surgery and after 12 month. Digital images were analyzed using Image J 1.33 open software and film-based images were digitalized via a video camera, light box and an image analysis program, as described by Braegger (1998; Braegger at al. 2004). All images were analyzed by an independent investigator who was blind to the implant material. The implant length was used as a reference measurement, and the implant chamfer 0.2 mm above the implant shoulder was used as the reference line for the bone-level measurement. Bone level was, therefore, defined as the distance from the reference point to the first bone-to-implant contact; mesial and distal bone-level changes in this region were considered as remodeling. Mesial and distal measurements were recorded and the mean of the two values was used. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success and Survival Rate of Both Study Implants Titanium Grade IV and Titanium Zirconium) According to Definition by Buser et al. 1990 | split-mouth design Implant success and survival rate according the definition by Buser et al. 1990 are: Absence of persistent subjective complaints, such as pain, foreign body sensation and/or dysaesthesia Absence of a recurrent peri-implant infection with suppuration Absence of mobility Absence of a continuous radiolucency around the implant Possibility for restoration | at 12, 24 and 36 months post surgery | 
| Soft Tissue and Safety Assessments | Modified Plaque Index (mPI) and modified Sulcus Bleeding Index (mSBI) according to Mombelli at al. (1987). Assessment to be perform at four sites per implant: lingual, buccal, mesial, and distal. mPI: 0=no plaque detected, 1=plaque only recognized by running a probe across the smooth marginal surface of the implant, 2=plaque can be seen by the naked eye, 3=abundance of soft matter. mSBI: 0=no bleeding when a periodontal probe is passed along the gingival margin adjacent to the implant, 1=isolated bleeding spot visible, 2=blood forms a confluent red line on margin, 3=heavy or profuse bleeding. Safety evaluations including recording of all complications, adverse events (AEs), and serious adverse events SAEs). Each AE and SAE will be assessed for severity and its potential relationship to the study device. | after 12, 24, and 36 month |