A Clinical Trial of Locally Made Titanium Miniplate and Screw in Maxillofacial Fractures Management
Phase: NA
Conditions: Maxillofacial Injuries, Maxillofacial Prosthesis Implantation, Fracture Fixation, Internal
Sponsor: Indonesia University

 
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CLINICAL STUDY PROTOCOL 
 
Study Title 
: A Clinical Trial of Locally-Made Titanium Miniplate and Screw In 
Maxillofacial Fractures Management 
Protocol Date  
: 07th October 2019 
Protocol Version 
: 1 
Ethics Number 
: KET-1085/UN2.F1/ETIK/PPM.00.02/2019 
 
 

 
2
Table of Contents 
INTRODUCTION AND RATIONALE ........................................................................................... 3 
Aim Of The Study ...........................................................................................................................4 
Study Hypothesis ...........................................................................................................................4 
OBJECTIVES AND OUTCOMES ................................................................................................. 5 
Primary Objective ..........................................................................................................................5 
Secondary Objective ......................................................................................................................5 
STUDY DESCRIPTION .............................................................................................................. 5 
Research Design .............................................................................................................................5 
Time And Place ..............................................................................................................................5 
STUDY POPULATION .............................................................................................................. 5 
Inclusion Criteria ............................................................................................................................5 
Exclusion Criteria ...........................................................................................................................5 
Dropout Criteria .............................................................................................................................6 
METHODOLOGY ..................................................................................................................... 6 
Subject Allocation ..........................................................................................................................6 
Intervention...................................................................................................................................6 
Miniplate And Screw Placement .....................................................................................................7 
Assessing Study Results ..................................................................................................................8 
Bone Density ......................................................................................................................................................... 8 
Screw Loosening ................................................................................................................................................... 8 
Tissue reaction ...................................................................................................................................................... 8 
Research Protocol ..........................................................................................................................9 
DATA ANALYSIS AND DATA PRESENTATION ........................................................................... 9 
 
 
 

 
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INTRODUCTION AND RATIONALE 
Maxillofacial trauma is one of the most devastating injuries for all plastic surgeon to face. Many 
problems occurred following this injury, such as loss of facial function, severe morbidity, high 
financial cost or even death.1,2,3 Motor vehicle accidents are the one who responsible for the 
most maxillofacial injuries, besides violence by other people. As many as 50–70% of people who 
survive traffic accidents have facial trauma4 with a peak incidence occurring between ages 20 
and 40 which are productive ages5 
Indonesia as one of the developed country in the world, maxillofacial fractures also caused by 
motor vehicle accidents. Data from several centers in Indonesia show that dr. Soetomo Hospital 
Surabaya taking care of 160 cases of maxillofacial fractures,6 while, Arifin Achmad Hospital 
Pekanbaru treated 413 facial trauma cases during 2010-2013. In Cipto Mangunkusumo Hospital 
Jakarta 494 patients were treated during 2015-2017. 
When there are displaced and unstable fracture segments leading to functional disturbance, for 
example, diplopia and malocclusion, open reduction and internal fixation using miniplate and 
screws are indicated to achieve the goal of maxillofacial fractures management. This internal 
fixator creates stability and allows early rehabilitation of the site of the fractures.7,8,9 
The miniplate and screw system for maxillofacial fractures that are widely used and available at 
Cipto Mangunkusumo Hospital are Biomet® and Osteomed®. Both brands are imported and 
similar in their quality. These brands, however, are very costly due to the importing expenses and 
luxury goods additional tax. Based on government law number 42, 2009, Chapter 5, imported 
medical devices are considered as luxury goods and will be charged with selling tax up to a 
minimum of 10 percent. Moreover, BPJS as national healthcare insurance in Indonesia comes to 
a serious deficit, therefore they demand the hospital to be more careful on patient management. 
In our hospital, through a division of "Kendali Mutu Kendali Biaya" (KMKB), they control the 
application of every medical implant, an expensive drug used and other expensive procedure. 
A locally-made miniplate and screw as internal fixators for maxillofacial fracture have been 
studied before on an animal. Previously conducted animal study the local miniplate and screw 
did not produce any wound complication with respect of infection, seroma, and hematoma 
during observation and the bone is healed according to the timeline.33 Moreover, local miniplate 
and screw fixation allow a not-inferior bone healing compared to import one in terms of bone 
density, muscle density, and peri-implant bone density.34 Furthermore, this locally-made 
miniplate and screw needs to face greater force and more complex system in the human body. 
Therefore, we will use it in patients with maxillofacial fractures, to evaluate the locally-made 
miniplate and screw efficacy while also reducing the cost that has to expend by our national 
health insurance.  
As stated in The Ministry of Health Regulations number 86, 2003 regarding The Road Map 
Development of Medical Equipment Industry, Ministry of Health demands local medical products 
to grow faster. On the contrary, medical devices currently available in Indonesia could not 
provide the demand for medical products. Ninety percent of medical products that are 
distributed in Indonesia are imported. In the globalization era, many products enter Indonesia 
easily, while the supply could not meet the demand, causing the price of these medical products 

 
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increases every year. As a result, the need for healthcare service and medical products supply 
does not meet.10  
Also addressing to the new national healthcare system number 27, 2014 regarding Technical 
Instructions System of Indonesian Case Base Groups, where medical coverage is not based on 
medical expenses but the grouping of diagnoses and treatment based on ICD-9, the high cost of 
medical products often complicate the hospital policy.11 
Therefore, as suggested by the Indonesian Ministry of Health, we are going to use our local plate 
and screw for maxillofacial fractures management to answer the balance of supply and demand 
of local medical products. On the other hand, it could help the government to reduce medical 
expenses. 
 
Aim Of The Study 
The aim of this experiment is to investigate the usage of the locally-made miniplate and 
screw are not inferior compared to the existing benchmark miniplate and screw in terms of 
bone healing, surrounding tissue reactions, and screw loosening. 
 
Study Hypothesis 
The locally-made miniplate and screw are not-inferior compared to the existing benchmark 
miniplate and screw in terms of bone healing, surrounding tissue reactions, and screw 
loosening. 
 
 

 
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OBJECTIVES AND OUTCOMES 
 
Primary Objective 
To evaluate bone density radiologically (in Houndsfield Unit) after plate and screw fixation with 
locally-made compared to existing benchmark miniplate and screw 
 
Secondary Objective 
- 
To evaluate if there is any loosening screw following both locally-made and existing 
benchmark miniplate and screw fixation. 
- 
To evaluate if there is any sign of local tissue reaction following both locally- made and 
existing benchmark miniplate and screw fixation. 
 
STUDY DESCRIPTION 
Research Design 
This study will be performed on patients with maxillofacial fractures. The study is a blind 
randomized clinical study comparing locally-made titanium plate and screws with the existing 
benchmark, BIOMET® miniplate, and screw.  After fixation, bone density, local tissue reactions, 
and screw loosening between these two devices at specific periods will be compared. 
 
Time And Place 
The clinical study will be conducted at Cipto Mangunkusumo Hospital, Jakarta, Indonesia from 
September 2019 – April 2020. Surgery will take place at Cleft Craniofacial Center Operating 
Theatre. It will be conducted by two consultants of craniomaxillofacial surgeons. 
 
STUDY POPULATION 
Inclusion Criteria 
- 
Midface fracture with the indication of surgery 
- 
Midface fracture sustained within 2 weeks  
 
Exclusion Criteria 
- 
Comminuted and defect fracture 
- 
Midface fracture on patients with systemic diseases affecting bone healing. 
- 
Midface fracture in children  
- 
Midface fracture in multiple trauma patients with neurological deterioration 

 
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Dropout Criteria 
- 
Patient who is unable to complete radiological evaluation after surgery due to lost to follow 
up or refuse to continue the evaluation will be replaced by another sample 
- 
Patient with signs of bacterial infection either locally or systemically or implant failure are 
not dropouts, their last data of observation will be included and analyzed (Last-Observation-
Carried-Forward (LOCF) method). 
 
METHODOLOGY 
 
Subject Allocation 
Subject is the fracture line found on the patient. The surgeon is not blinded on which miniplate 
is going to use because the miniplate has different characteristic. 
 
Intervention 
Pre-operatively 
- 
Patients will sign the informed consent sheet and declare that they want to be enrolled as 
subjects and obey all the instructions given postoperatively 
- 
The patients will shower with chlorhexidine 4% 27 soap 1 day before surgery 
- 
An empiric antibiotic will be administered 1 hour preoperatively: intravenous injection of 
Ampicillin Sulbactam 1.5 gr/IV 28 to prevent postoperative infection. 
 
Intra-operatively 
- 
All patients will be treated under general anesthesia. 
- 
After induction of anesthesia, the operating field is disinfected with povidone-iodine 
- 
Draping the patient, exposing only the area of surgery 
- 
Local anesthetic solution with a vasoconstrictor is administered along the incision line area 
for homeostasis 
- 
Maxillary mandibular fixation is performed to maintain the occlusion 
- 
Midface fracture site approach through an intra-oral or extra-oral incision according to the 
accessibility at that time and may differ for every patient 
- 
The fractured segment is reduced into proper position using Carrol-Girrard, hook, elevator or 
Rowe disimpaction forceps. 

 
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- 
The surgeon will received a seal envelope contain an instruction to use locally-made miniplate 
or existing benchmark miniplate and then it will be bend as desired based on the fracture site 
contour 
- 
The surgeon will place the miniplate on the fracture site based on AO/CMF point fixation 
sequence. 
- 
The plate is tapped manually with gentle pressure. The screw is inserted into the hole using 
a screwdriver and held parallel to the long axis of the drill hole. 
- 
The steps of drilling, tapping and screwing all panel holes are repeated for all screw holes 
followed by the closure of the incision with usual manner. 
- 
The maxillary mandibular fixation is removed and the jaw is manipulated to evaluate the 
occlusion and also measure the maximal mouth opening. Forced-duction test is performed 
when there is a placement of the plate on the orbital rim. 
- 
The maxillary mandibular fixation is maintained for approximately 2 weeks and evaluates 
once a week during patient visit to the outpatient clinic 
 
Post-operatively 
- 
Intravenous injection of Ampicillin Sulbactam 1.5 gr every 6 hours is given for 1-2 days, then 
when the patient is discharged it is replaced by Amoxicillin/clavulanic acid 625 mg orally every 
8 hours for another 7 days post-operatively 
- 
Intravenous injection of Paracetamol 1 gr every 8 hours is given for 2 days followed by oral 
tablets 500 mg every 8 hours as needed for another 7 days for pain control 
- 
All patients undergo a non-contrast head CT scan on day one postop as a baseline 
- 
All patients are discharged two days after surgery and instructed to have liquid diet for 2 
weeks post-operatively 
- 
Patients will visit the outpatient clinic once a week for 3 weeks. Sign of bacterial infection or 
local tissue reaction will evaluate by the end of 3rd week 
- 
All patients performed a non-contrast head CT scan at 3 months postoperatively. 
 
Miniplate And Screw Placement 
Once a patient lies down on the operating table under general anesthesia, the surgeon will 
identify the fracture segment. The surgeon will received a seal envelope contain an instruction 
to use locally-made miniplate or existing benchmark miniplate to be placed on the fracture site 
according to a predetermined randomization list. The decision where to place the locally made 
miniplate or existing benchmark miniplate depends on AO/CMF point of fixation sequence. 
 

 
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Assessing Study Results 
After completing the procedure, subjects will undergo non-contrast head CT scan evaluation 
immediately after surgery as a baseline, and by the end of 3rd months post-operation. Afterward, 
a radiologist consultant as a blinded independent evaluator will assess the bone density score in 
each subject. A score sheet will be given to the assessor. Subjects will also be instructed to visit 
the outpatient clinic once a week for 3 weeks post-operatively to evaluate their appearances 
clinically if there is any sign of bacterial infection or local tissue reaction that will be taken care 
of by consultants of craniomaxillofacial surgeons. 
 
Bone Density 
Bone density of each subject will be recorded in Hounsfield Unit (HU). The bone density score of 
each subject will be noted and scores between the two brands will be compared. The scores will 
be evaluated by a radiologist consultant  and act as an independent evaluator after the subject 
has completed all their Head CT evaluation.29, 30 
Screw Loosening 
Screw loosening will be recorded, whether it is present or not. It will be evaluated by a radiologist 
consultant after the subject completed all their Head CT evaluation.  
Tissue reaction 
Local tissue reactions such as edema, bacterial infection, or any other signs of the inflammation 
process, will be recorded by the end of the 3rd week during patient’s visit outpatient clinic.  It will 
be evaluated by consultants of craniomaxillofacial surgeons and. 
 

 
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Research Protocol 
 
 
DATA ANALYSIS AND DATA PRESENTATION 
Data on bone density are quantitative, all scores from points of evaluation group will be collected, 
and scores for the dependent variables between groups will be statistically compared using 
independent t-test or Mann Whitney test depending on the distribution of the data is normal or 
not. Other findings will be presented using descriptive statistics. 
 
Table 2. Dummy table of bone density (HU) in group I (Locally-made miniplate and screw) versus 
group II (existing benchmark miniplate and screw) at different observation periods. 
Time (Postop) 
Group I (Mean 
±SD) 
Group II (Mean 
±SD) 
p-Value* 
Bone Density 
Immediately post op 
 
 
 
Three months post op 
 
 
 
*Statistically significant difference versus baseline reading if p-value ≤ 0.05 HU=Hounsfield unit. 
 

 
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Table 3. Dummy table of local tissue reaction and screw loosening presence in group I (Locally-
made miniplate and screw) versus group II (existing benchmark miniplate and screw) at different 
observation periods. 
Time (Postop) 
Group I 
(n=60) 
Group II 
(n=60) 
Local tissue reaction presence 
3rd week 
 
 
Screw loosening presence 
Immediate post op 
 
 
2 months post op 
 
 
 
 
 

 
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