Single-stage Surgery Using the BI300 Implant

Over the last few decades, the classical two-stage surgical procedure for inserting bone-anchored hearing implants (BAHIs) has been modified in adults into a single-stage procedure. This approach has several advantages since it avoids a second surgical procedure. The single-stage approach is proven to be safe and feasible in adults and is nowadays referred to as the standard surgical technique in adults. Despite favorable outcomes and advantages of the single-stage surgery, most Ear Nose Throat (ENT)-surgeons still perform two-stage surgery when inserting BAHI in the pediatric population. Therefore, the aim of this study is to compare implant loss between single-stage BAHI surgery and two-stage BAHI surgery in children aged 4 to 9 years.

General description:

A prospective comparative study with historical control group will be performed.The test group will consist of 22 children aged 4-9 years old who are found to be suitable candidates for treatment with a BAHI (BI300 implant and BA300 abutment). The control group consists of approximatley 50 children, aged 4-9 years old, who already underwent insertion with a wide diameter implant between 2012 and 2018. In the test group, BAHI insertion will be performed using single-stage surgery. Patients in the control group already underwent BAHI insertion using two-stage surgery.

Recruitment and consent:

All children planned for implantation with bone anchored hearing implants will be screened for inclusion in the present study. Patients who meet the inclusion criteria will be approached for participation by their ENT-specialist, after patients' and parents/caretakers' approval they will be informed and screened for participation by one of the researchers. The study protocol will be discussed with the potential study participant and his/her parents/caretakers by the researcher. The potential study participant and his/her parents/caretakers will be given/sent the Informed Consent Form to read. Potential study participants will be encouraged to discuss the study with family members and personal physician(s) before deciding whether to participate in the study. Patients and their parents/caretakers have 14 days to consider their decision. In order to participate in the study, both parents/caretakers need to sign the informed consent form.

Data handling:

Data captured will be recorded in Castor using electronic Case Report Forms (eCRFs). All data, patient and product related, must be accurately recorded in the eCRF by the delegated site staff. All users of the Castor system have personal, password protected accounts allowing tracking of all data entry in the system. Data management and data cleaning will be performed in the eCRF using the queries function to ensure traceability of all data entry and changes by the assigned data manager. Data including patient identifying information (i.e. name, initials, birth date) will be stored on a secured network drive using a code. Only the investigator who has the code can correlate the data with the patient's name and date of birth. It is the responsibility of the investigator to make sure that patient identification listings with patient code and identity are kept. Raw measurement data and other data such as historical information will be storedin the patient file, since data may be partly acquired and/or evaluated during standard patient care to limit the amount of extra procedures and hospital visits. For data analyses, data will be exported and stored in a digital research environment, separate from the key to the code. After completion of the study data collection and final monitoring visit, the electronic database will be locked and exported to SPSS format, which will be archived for 15 years after completion of the study. The coded study data will be archived separately from the key to the subject code in a secured digital research environment, also for a period of 15 years.

Reporting (severe) adverse events:

The investigator will report the Severe Adverse Events (SAEs) through the web portal ToetsingOnline to the accredited Medical Ethical Committee (METC) that approved the protocol, within 7 days of first knowledge for SAEs that result in death or are life threatening followed by a period of maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported within a period of maximum 15 days after the investigator has first knowledge of the serious adverse events.

Device deficiency:

Inadequacy of an investigational medical device related to its identity, quality, durability, reliability, safety or performance. This may include malfunctions, use error, or inadequacy in the information supplied by the manufacturer. Device deficiency's will be logged together with an assessment by the investigator and reported to the manufacturer where applicable.

Follow-up of adverse events:

All Adverse events (AEs) will be followed until they have abated, or until a stable situation has been reached. Depending on the event, follow up may require additional tests or medical procedures as indicated, and/or referral to the general physician or a medical specialist. SAEs need to be reported until the end of study within the Netherlands, as defined in the protocol.

Monitoring and Quality Assurance:

In accordance with the guidelines of the 'Dutch Federation of university medical centers' (NFU) for monitoring of studies with negligible risk, a qualified monitor of another department of the Radboudumc, who is not part of the research team of this study, will be appointed. 28% of informed consents, 10% of inclusion and exclusion criteria (and three subjects who were enrolled first), 10% source data verification, reported SAEs and 10% of participants with regard to missed SAEs will be monitored.

Statistical analysis:

The main analyses will be the comparison between the test group, in which single-stage surgery is performed and the control group undergoing two-stage surgery.

Concerning the primary outcome, the proportions of implant loss in the test and control group will be compared using an exact binominal test and a one tailed confidence interval of 95%.

Secondary outcome measures will be compared between groups using the unpaired t-test (normally distributed data or Mann-Whitney U tests (not normally distributed data) for continuous variables, Mantel Haenszel chi-square test for ordered categorical variables, Fisher's exact test for dichotomous variables and Chi-square test for non-ordered categorical variables. If significant differences are found for baseline variables between the test group and the control group a complementary analysis between the two groups will be performed with adjustment for these variables.

Handling of missing data for secondary and tertiary endpoints (especially applicable for control group data), depends on the reason why this data is missing and on the amount of missing data. Therefore decisions on handling of missing data will be made after all data is collected.

All tests will be performed using a confidence interval of 95% and a significance level of 0.05.

Eligibility Criteria:
Inclusion Criteria test group

* Age 4-9 years
* Indication for percutaneous bone-anchored hearing implant surgery with a BI300 implant
* Insertion using the linear incision technique

Inclusion criteria Control group:

* Children who underwent implantation of a wide diameter implant using two-stage surgery between 2012 and 2018 at the Radboudumc
* Age 4-9 at the time of surgery
* Linear incision technique was used during surgery

Exclusion Criteria Test group

1. Inability to show up at all follow-up visits
2. Patients undergoing re-implantation
3. Diseases, syndromes or treatments known to compromise the bone quality at the implant site, e.g. radiotherapy, osteoporosis, diabetes mellitus.
4. Insufficient bone thickness ≤1mm, since conversion to two-stage surgery will be advocated

Exclusion Criteria Control group

1. Follow-up duration less than 1 year.
2. Diseases, syndromes or treatments known to compromise the bone quality at the implant site, e.g. radiotherapy, osteoporosis, diabetes mellitus (at moment of implantation)