This study was designed as a randomized, controlled, multicenter clinical trial to evaluate non-inferiority of early loading compared to conventional loading of dental implants with a chemically modified SLA surface placed in single tooth gaps, involving three centers in Japan (Tokyo Medical and Dental University (TMDU), Tokyo Dental College Chiba Hospital (TDCC), and Tokyo Dental College Suidobashi Hospital (TDCS)). The study was conducted in accordance with the Declaration of Helsinki (1964 and all subsequent amendments), the Japanese Pharmaceutical Affairs Law, the Ordinance Concerning the Standards for Clinical Trials on Medical Devices (2005 MHLW Ordinance No. 36), and the relevant notifications and protocol. The study was approved by the Institutional Review Boards of the medical institutions involved. Written informed consent was obtained from all patients. The study was registered at www.clinicaltrials.gov.

Patients were enrolled according to strict pre-defined inclusion and exclusion criteria. The most important inclusion criteria were as follows: age ≥20 years, single tooth gaps in molar or premolar in the mandible or maxilla, bone quality I–III and sufficient bone quantity to allow implant placement, and substantially healed extraction sockets (at least 16 weeks after tooth extraction).

Important exclusion criteria fell into two categories: systemic and dental. The most important systemic exclusion criteria were as follows: systemic disease, e.g., diabetes mellitus; serious internal medical problems, e.g., cardiac or cerebral infarction; bone disorders, e.g., metabolic bone disease, temporomandibular joint disorders, treatable changes in the oral mucosa, local root remnants, xerostomia, and bisphosphonate medication; inadequate wound healing capacity, prolonged therapy-resistant functional disorders, and steroid use or irradiation; uncontrolled bleeding disorders and anticoagulation drugs/hemorrhagic diatheses; psychoses, drug or alcohol abuse, or titanium allergy (based on patient declaration); smoking >10 cigarettes per day; pregnancy and/or breastfeeding; participation in another clinical trial during or within 30 days before this trial; unwillingness or inability to follow the investigator’s instructions; or any other conditions that might prevent study completion in the opinion of the investigator. The dental exclusion criteria were as follows: untreated dental and serious periodontal lesions; severe bruxism or clenching habits; existing implants in the adjacent position; removable dentures or un-restored tooth gaps in the opposing dentition; probing pocket depth ≥4 mm at a tooth immediately adjacent to the dental implant site; major simultaneous augmentation procedures; requirement for maxillary sinus lift, socket preservation, or ridge augmentation; and failure of a previous implant at the planned implant site (Table 1).