Short-term safety and effectiveness of the mCLIP partial prosthesis

Purpose This multicentric, retrospective study aimed to analyze the short-term safety and effectiveness of the mCLIP Partial Prosthesis. Methods Patients underwent tympanoplasty with implantation of a mCLIP Partial Prosthesis. Follow-up examination included ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA4). The post-operative PTA4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. Thus, the follow-up times of each study center were different, which resulted in different follow-up times for the audiological analysis and for adverse events (AE). Results 72 (66 adults, 6 children) patients were implanted with the mCLIP Partial Prosthesis. 68 (62 adults, 6 children) patients underwent audiological examination; all 72 patients were examined for adverse events. All patients (N = 68): 72.1% of the patients showed a PTA4 ABG of ≤ 20 dB. Individual post-operative bone conduction (BC) PTA4 thresholds were stable in 67 patients. The mean post-operative follow-up time was 78 ± 46 days. Children (N = 6): 5 out of 6 children showed a PTA4 ABG of ≤ 20 dB. None of the children reported a BC PTA4 deterioration of > 10 dB HL after the implantation. The mean post-operative follow-up time was 101 ± 45 days. Adverse events (all patients, N = 72): 15 (14 adults, 1 child) patients had AEs (27 AEs and 2 Follow-Ups). The mean post-operative follow-up time was 375 days. Conclusion Clinical data show satisfactory audiological parameters after implantation of the mCLIP Partial Prosthesis. The prosthesis is safe and effective for implantation in children and adults. Trial registration number NCT05565339, 09 September 2022, retrospectively registered.


Introduction
Passive middle ear implants (PMEIs) are used to reconstruct the ossicular chain to improve hearing in patients.PMEIs are designed to replace the ossicles and restore mechanical sound transmission from the tympanic membrane to the oval window.In addition to alloplastic materials, PMEIs include metals (titanium, platinum, gold), plastics (polyamide, polyethylene), Teflon®, and ceramics (hydroxyapatite, oxide ceramic, carbon, calcium phosphate ceramic, glass ceramic) [1].Titanium is easy to implant, has a low extrusion rate and good tissue compatibility [2], and provides good functional results [3].Titanium PMEIs have been on the market since 1994 [4], and ossicular chain reconstruction is considered the standard surgical method for hearing restoration.
Our study provides results on patients implanted with the new mCLIP Partial Prosthesis (MED-EL, Innsbruck, Austria).The mCLIP Partial Prosthesis is made of titanium and was introduced to the market in August 2020 (Fig. 1).

mCLIP partial prosthesis design
The mCLIP Partial Prosthesis is made of medical titanium, grade 2. The head plate has a diameter of 2.6 mm and a thickness of 0.1 mm.The mCLIP Partial Prosthesis consists of 4 longer coupling structures with a length of 1.6 mm and 4 shorter coupling structures with a length Extended author information available on the last page of the article 1 3 of 1 mm.For the distance between the stapes head and the tympanic membrane, called functional length, is the prosthesis available from 0.75 -3.5 mm and determines the 10 length versions of the prosthesis: 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 3.0, 3.5 mm (Fig. 1).

Study design
This multicenter, retrospective follow-up study included 72 patients (72 ears), in which each patient served as his or her own control.All 72 patients were assessed for adverse events (AE); 4 of the 72 patients were excluded from the audiological analysis because of missing audiological data.For the analysis, patients implanted with the mCLIP Partial Prosthesis (regardless of implanted prosthesis length) until end of December 2022 were included.

Follow-up time
Patients were evaluated pre-and post-operatively (1 preand 1 post-operative audiological measurement).A postoperative minimum and maximum follow-up period was not specified.Therefore, follow-up times varied among study centers, resulting in different follow-up times for audiologic analysis and AE analysis.The mean post-operative followup time of all patients was calculated.Post-operative PTA was calculated as a four-frequency mean of 0.5, 1, 2, and 3 kHz (PTA 4 ).

PTA 4 ABG
Babighian et al. defined a post-operative PTA 4 ABG of ≤ 20 dB as successful rehabilitation [1].The minimum success rates found in the scientific literature for a titanium partial ossicular replacement prosthesis was reported by Quesnel et al. -53.8% of the patients achieved a PTA 4 ABG of ≤ 20 dB post-operatively [2].Based on [1] and [2] a postoperative PTA 4 ABG of ≤ 20 dB by ≥ 53.8% of the patients was considered a successful outcome four our study.

BC PTA 4
The individual differences (Δ) between bone conduction (BC) post-operative and pre-operative PTA 4 were calculated to determine safety of the procedure.

Adverse events (AE)
All surgical-, procedure-and device-related AEs in the operated ear that occurred intra-and post-operatively were collected.

General information
PTA 4 ABG and adverse events were analysed descriptively.BC PTA 4 was calculated inferentially.Graphs were created with GraphPad Prism 7 (GraphPad Software, Inc.).

Children (N = 6):
The 6 children (3 female, 3 male) had a mean age of 12.7 ± 2.4 years (range: 9-16 years) at the time of implantation.4 out of 6 children were implanted in the left ear and 2 in the right ear. 3 children suffered from MHL and 3 from CHL.In 2 cases it was not reported whether a tympanoplasty sizer was used, in further 2 cases no tympanoplasty sizer was used, and in other 2 cases a MED-EL tympanoplasty sizer was used.

Audiometric results:
PTA 4 ABG, all patients (N = 68):  2).The mean post-operative PTA 4 ABG of all 68 patients was 16.3 ± 10.9 dB.The first endpoint, improvement in postoperative PTA 4 ABG of ≤ 20 dB by ≥ 53.8% of the patients was achieved.Figure 2 shows the PTA 4 ABG results for all patients, as well as the pre-and post-operative AC and BC thresholds at the individual frequencies.

All patients (N = 72)
The mean post-operative follow-up time of the 72 patients was 368 ± 177 days (range: 0-666 days; median: 375 days).15 (20.8%) of the 72 patients had AEs (27 AEs and 2 follow-ups).One (1.4%) underage patient showed recurrent cholesteatoma; a revision surgery was performed and the mCLIP Partial Prosthesis was replaced with a total ossicular replacement prosthesis (patient 23).Another patient (1.4%) showed a prosthesis extrusion in combination with hearing reduction (patient 24) and was treated with a hearing aid.One patient (1.4%) suffered from a fungal infection in the mastoid cavity and the headplate of the prosthesis started to migrate (patient 31) (Table 3).Due to the retrospective design of the study, there was no further information available regarding the current status of the adverse events.

Children (N = 6)
The mean post-operative follow-up time of the 6 children was 549 ± 46 days (range: 478-606 days; median: 555 days). 1 (patient 23) out of 6 children had an AE, which is described above.seven clip prosthesis legs encompass the stapes head and come together between the crura; two (shorter) of the legs stabilize the prosthesis from the rear and one (shorter) leg from the front [3].[12].In our study the mean BC PTA 4 threshold was for all patients (N = 68) 21.4 ± 13.8 dB HL pre-operatively and 18.9 ± 13.9 dB HL post-operatively, which is in accordance with the results of Birk et al. [12].Gostian et al. reported for the early-and late follow-up that BC thresholds had no significant differences and that the mean changes in BC PTA 4 thresholds were < 10 dB HL at all frequencies [7].Kahue et al. reported that no patient experienced a BC PTA 4 shift of > 15 dB HL for the shortand long-term follow-up [11].Birk et al. [12], Gostian et al. [7], and Kahue et al. [11] included children, but they did not report separately for children.There is no consensus on comparison of post-operative sensorineural hearing loss (SNHL) [7,11,12].However, when comparing the results of our study to Gostian et

Adverse events
Three of the 72 patients (27 AEs + 2 Follow-Ups) showed 3 adverse events, which should be discussed.One patient (1.4%) showed a recurrent cholesteatoma, which resulted in the replacement of the mCLIP Partial Prosthesis with a total ossicular replacement prosthesis; this revision surgery was not device related (patient 23).One (1.4%) patient had an extrusion in combination with a hearing reduction.A hearing device was recommended or was already used after the recommendation (patient 24).One patient (1.4%) suffered from an infection, and the prosthesis started to migrate (patient 31).
Yu et al. evaluated the effectiveness and the stability of the partial ossicular replacement prosthesis using a metaanalysis.The post-operative follow-up time was < 3 years for short-term and ≥ 3 years for long-term.3.3% of the patients had an extrusion at the short-term follow-up.6.7% of the patients had an extrusion at the long-term follow-up.No information on the revision surgeries was given [13].
Omar et al. reported that 3% of the children had an extrusion of the prosthesis.The mean post-operative follow-up time ranged from 12-72 months [10].
In our mean follow-up period of 368 ± 177 days, it is not significant to draw a valid conclusion about the rates of revision surgeries, extrusions, and migrations.However, if our revision rate (1.4%) and our extrusion rate (1.4%) is compared to the rates of Yue et al. [13] and Omar et al. [10], they are in accordance.The rates of revision surgeries, extrusions, and migrations increase with the length of the post-operative follow-up time, which was demonstrated by the long-term safety of Yu et al. [13].
The type of partial ossicular replacement prosthesis determines the stability of the connection between the tympanic membrane and the stapes.The availability of the malleus handle, the mucosal status of the middle ear and the status of the stapes footplate, all have an important impact on the post-operative hearing results [14].
Further detrimental influences on post-operative hearing include mucosal fibrosis, drainage, revision ear surgeries and the type of surgical technique used [15].An intra-operative and post-operative assessment of the quality of the tympanoplasty surgical technique is limited [16], and surgical interventions cannot solve every problem in the middle ear.In most cases, the mucosal function of the middle ear and the eustachian tube cannot be reconstructed completely, which results in insufficient ventilation and thus insufficient vibration of the restored middle ear [17].In general, ossicular reconstruction depends on several anatomical factors such as aeration of the middle ear, inflammatory status of the middle ear, remnants of the ossicles, condition of the tympanic membrane (e.g., size, defect, thickness of the tympanic membrane graft), status of mucosa, experience of the surgeon and follow-up period [18], that's why surgery results are often difficult to compare.

Conclusion
In this short-term study, 72.1% of patients achieved a postoperative PTA 4 ABG of ≤ 20 dB.Only one patient had a BC PTA 4 decrease of > 10 dB HL (16.3 dB HL).The rates of performed and suggested revision surgeries, the rates of extrusions and migrations was in each case one (1.4%)patient.The follow-up time is too short to draw a final conclusion about these rates.A long-term follow-up study should be performed regarding adverse events.In summary, the mCLIP Partial Prosthesis is safe and effective for all patients (adults and children).

Fig. 1
Fig. 1 mCLIP Partial Prosthesis (left); schematic drawing of the mCLIP Partial Prosthesis (right).The titanium prosthesis consists of a contourable head plate and a standard clip.It is available in 10 different length versions

PTA 4 ABG
Clinical data of our study show satisfactory audiological parameters after the implantation of the mCLIP Partial Prosthesis with a mean PTA 4 ABG of 16.3 ± 10.9 dB (N = 68) and stable BC PTA 4 thresholds in 67 of the 68 patients.During a similar trial, Gostian et al. conducted a retrospective study with 47 patients (47 ears) implanted with the Clip Partial Prosthesis Dresden Type (Heinz Kurz GmbH, Dusslingen, Germany), showing a mean post-operative PTA 4 ABG of 20.9 ± 10.4 dB at the early follow-up at 21.1 days (range: 23.1-25.5 days).The clip design allows for stable placement and removal of the partial prosthesis without necrosis or other damage to the stapes head[7].Our mean PTA 4 ABG results (N = 68, 16.3 ± 10.9 dB) with the mCLIP Partial Prosthesis are comparable to the short-term results of Gostian et al. (20.9 ± 10.4 dB).Zaoui et al. conducted a prospective study with 52 patients implanted with a Dresden type clip partial prosthesis (Kurz, Germany).The patients were followed for 4 weeks.The mean post-operative PTA 4 ABG was 22.4 ± 3.1 dB[8].The mean PTA 4 ABG of our (16.3± 10.9 dB) study was favourable to the results ofZaoui et  al. (22.4 ± 3.1 dB) [8].Neudert et al. reported of 29 patients implanted with a titanium clip prosthesis.The mean post-operative PTA 4 ABG was 18.8 ± 1.6 dB.66% of the patients had a post-operative PTA 4 ABG of ≤ 20 dB [9].Our mean PTA 4 ABG results and the percentage of the mCLIP Partial Prosthesis patients which reached a PTA 4 ABG of ≤ 20 dB is in accordance with results of Neudert

Table 1
Demographics of the patients (N = 72)

Discussion History of the clip mechanism development
[4]sthesis plate and shaft[5].The clip design of the mCLIP Partial Prosthesis is based on that of the titanium angular clip prothesis[4].Hüttenbrink et al. reported that more contact points between the prosthesis and stapes result in a more beneficial anchoring of the prosthesis.Four (longer) of the

Table 3
Adverse events Birk et al. evaluated the CLIP Partial FlexiBAL prosthesis (Heinz Kurz GmbH, Dusslingen, Germany) in 60 patients (62 ears).The first follow-up was in mean 19 days after the surgery.The mean BC PTA 4 threshold was 20.2 dB HL pre-operatively and 18.1 dB HL post-operatively.The postoperative BC was stable in all 62 ears al. (mean changes in BC PTA 4 thresholds were < 10 dB HL at all frequencies), and Kahue et al. (no patient experienced a BC PTA 4 shift of > 15 dB HL), there is only one (1.5%)patient (patient 11, adult) with a BC PTA 4 deterioration of ≥ 10 dB HL (16.3 dB HL).