Prospective, Single Center PMCF-study on the Performance and Safety of the CranioFix®2 System Used for the Fixation of Craniotomized Bone Flaps and Fractures to the Neurocranium
Conditions: Skull Fractures
Sponsor: Aesculap AG

CRANFLAP AAG-O-H-2043 
 
CLINICAL INVESTIGATION REPORT 
Study No: AAG-O-H-2043 
 
 
Investigational Medical Device:  
CranioFix®2 system  
Device Class:  
The instruments belong to the medical device 
class I, reusable surgical instruments for 
temporary application (FF103R, FF104R, FF105R) 
as well as non-invasive product (FF494R). The 
implants belong to the product group of 
neurosurgical cranial implants are classified in 
medical device class III as implantable device for 
long-term use in direct contact with the central 
nervous system.  
Sponsor:  
Name, Affiliation & Contact Details:  
Aesculap AG Am Aesculap-Platz 78532 Tuttlingen 
Germany Study Manager: Diana Kupferschmid 
Phone: +49 7461 95-31225 e-mail: 
Diana.Kupferschmid@aesculap.de  
Coordinating Investigator:  
Name & Affiliation:  
Not applicable  
Principal Investigator: Name & Affiliation:  
Minou Nadji-Ohl, Oberärztin Sektionsleitung 
Neuroonkologie und klinische Studien 
Neurochirurgie Katharinenhospital Klinikum der 
Landeshauptstadt Stuttgart gKAöR , 
Kriegsbergstrasse 60, 70174 Stuttgart, Germany 
Telephone: +49 711 278-01  
Author(s) of the report:  
Diana Kupferschmid, Aesculap AG  
Dept.: Medical Scientific Affairs 
Am Aesculap-Platz  
78532 Tuttlingen Germany  
Phone: +49 7461 95-0,   
e-mail: studies@aesculap.de  
Indication Studied:  
Fixation of craniotomized bone flaps and fractures 
to the neurocranium.  
Study Design:  
Prospective, single-arm, single center PMCF-
study  
Development Phase:  
Post-Market.  
After CE-marking.  
Study Initiation Date:  
22.03.2022 (First Patient In, FPI)  
 
 

Date of Early Study Termination:  
Not applicable  
Study Completion Date:  
27.10.2023 (Last Patient Out, LPO)  
Report Issue Date:  
2024-09-24  
 
 
 
Brief Synopsis  
Title of Study:  
Prospective, single center PMCF-study on the 
performance and safety of the CranioFix®2 system 
used for the fixation of craniotomized bone flaps 
and fractures to the neurocranium.  
Investigators:  
Minou Nadji-Ohl  
Study Centre(s):  
Klinikum Stuttgart – Katharinenhospital 
Neurochirurgische Klinik Kriegsbergstraße 60 
70174 Stuttgart Germany  
Publication (reference):  
Not applicable  
Studied period:  
First patient in: 22.03.2022  
Last patient out: 27.10.2023  
Study period approximately 19 months.  
Objectives:  
To evaluate the performance of the CranioFix®2 
system in daily clinical practice when used as 
intended, different safety and efficacy parameters 
were used. Primary endpoint was the 
postoperative stability of the bone flap after 
fixation.  
Methods and study design:  
Prospective, single-arm, single-center post-
market clinical follow-up study under daily clinical 
routine.  
Number of patients (planned and analysed):  
Planned: 25 patients  
Recruited: 25 patients  
Analyzed: 25 patients  
Diagnosis and main criteria for inclusion:  
Inclusion criteria:  
Written informed consent  
Age ≥ 18 years  
Use of CranioFix®2 system according to IfU  
Planned postoperative MRI within clinical routine  
 
 

Exclusion criteria:  
Pregnancy  
Patients with hypersensitivity to metals or 
allergies to the implant materials  
Inflammations in the region of the implant site  
Bone conditions that rule out the application of 
CranioFix®2 titanium clamps  
Use with artificial cranial bone flaps  
Bone tumors in the area supporting the implant  
Degenerative bone diseases  
Missing dura mater  
Application in the facial skull (viscerocranium) 
and in the orbital or skull-base region  
Combination of implant components from 
different manufacturers, i.e. additional use of 
plates and screws on the same bone fragment  
 
  
Test product  
CranioFix®2 titanium clamp system consists of 
sterile CranioFix®2 titanium clamps for single use 
and reusable neurosurgical instruments for the 
application of titanium clamps.  
Implants:  
clamp ∅ 11 mm (FF490T/FF490T-UNI)  
clamp ∅ 16 mm (FF491T/FF491T-UNI)  
clamp ∅ 20 mm (FF492T/FF492T-UNI)  
 
Instruments:  
CranioFix®2 cutting forceps / pin cutter (FF103R)  
CranioFix®2 removal forceps (FF104R)  
CranioFix®2 holding forceps (FF105R)  
CranioFix®2 applicator (FF494R)  
 
Duration of treatment:  
Study duration per patient about 3 months (±2 
months)  
Reference therapy:  
Not applicable  

Criteria for evaluation:  
Clinical Performance / Efficacy:  
Safety:  
Primary endpoint: Stability of the bone flap after 
fixation, postoperative.  
Primary variable: Planarity of the bone flap after 
implantation. Rate of the patients in which a 
dislocation of the bone flap occurs (defined as the 
height of tilting (depression / protrusion) greater 
than the bone width).  
Secondary endpoints: Safety parameters:  
Incidence of adverse events (intra- and 
postoperative, until follow-up) e.g. foreign body 
reactions, infections, injury to the dura, injury to 
the scalp, epiduralhaematoma, wound healing 
disorders. Special focus on (serious) adverse 
events with (possible) relation to the 
investigational product  
 
Performance parameters:  
Handling of CranioFix®2 system (intraoperative) on 
a Likert scale 1 to 5  
Stability of the bone flap after fixation 
(intraoperative- and postoperative) on a Likert 
scale 1 to 5  
Cosmetic outcome (intra- and postoperative) on a 
3 point scale  
 
Statistical Methods:  
All data was analyzed descriptively by means of 
tables, figures, listings and statistical tests if 
appropriate. 95% confidence intervals were 
calculated for primary and secondary endpoint 
rates where appropriate.  
SUMMARY - CONCLUSIONS  
CLINICAL PERFORMANCE / EFFICACY RESULTS:  The aim of this observational study was to collect 
systematically and proactively data regarding the 
performance of the CranioFix®2 system, like 
adverse events (AEs), handling and cosmetic 
outcome, under daily clinical practice when used 
as intended by the manufacturer. The patients 
were followed up for 3±2 months.  
The study included patients undergoing a surgery 
with fixation of craniotomized bone flaps and 
fractures to the neurocranium using the 
CranioFix®2 titanium clamp system.  

In all 25 cases, the indication for the cranial repair 
was a tumor resection.  
The procedures were performed by ten surgeons. 
The discharge and follow-up examinations were 
conducted by the previously defined investigative 
team.  
  
The primary parameter was the postoperative stability of the bone flap after fixation. During all visits 
there were no negative evaluations given regarding the stability of the bone flap. The primary variable 
was the planarity of the bone flap after implantation, evaluated as the rate of the patients in which a 
dislocation of the bone flap occurred – defined as the height of the tilting (depression / protrusion) 
greater than the bone width. In 24 cases, the bone flap was assessed as “in level” either at the follow-up 
visit and/or at the discharge visit. The one patient for whom no assessment was given died after surgery 
before discharge.  
The overall handling of the CranioFix®2 system was rated as “very good” (12 cases), “good” (12 cases) or 
“acceptable” (1 case) by the participating surgeons. In all cases there was no bad evaluation of the 
cosmetic outcome stated – neither by the surgeon nor by the patient.  
SAFETY RESULTS:  
Three AEs were reported, of which two were 
classified as serious adverse event (SAE).  
In none of those cases a possible causal 
relationship to the CranioFix®2 system was 
determined.  
In all three cases a probable causal relationship to 
the surgical procedure was determined.  
CONCLUSION:  
This study demonstrates that the CranioFix®2 
system, used for the fixation of craniotomized 
bone flaps and fractures to the neurocranium, 
provides a safe handling and a firm and stable 
fixation of the bone flap with a good clinical and 
cosmetic outcome  
Date of the report:  
2024-09-24  
 
 
Statistical analysis methods  
All data was analyzed by means of tables, figures, listings and statistical tests if appropriate. The final programming 
was performed after closure of the database by use of the statistical software package SAS Viya software version 
V.04.00 (SAS Institute Inc., Cary, NC, USA).  
All available data was analyzed.  
For summarized results (e.g. mean, standard deviation), the number of used data is mentioned.  
The patient data was identified by the patient ID assigned during data entry, which incorporates the study center ID.  
The statistical analyses were performed according to following principles:  

Variables with metric or ordinal scale were summarized with:  
• 
Number of observations used (N)  
• 
Minimum (Min)  
• 
Maximum (Max) 
• 
Median 
• 
Mean  
• 
Standard deviation (StD) 
• 
(optional) 95% confidence interval of the median 
Categorical variables were summarized with:  
• 
Absolute frequency (n)  
• 
Relative frequency (%)  
• 
(optional) Nmiss  
• 
(optional) 95% confidence interval of the relative frequency  
 
A separate category "N/A" was used for missing values.  
Missing data was analyzed as such and was not replaced by estimates.  
Statistical figures and plots (e.g. box-plot, bar-chart) were presented where appropriate.  
The statistical evaluation of the study data was carried out by the sponsor. A final biometrical report was set up.  
The following tables inclusively descriptive statistics were planned,  
• 
Demographic data  
• 
Results  
• 
AEs listing