Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03533231 |
| Other study ID # |
FDASU-RECID011508 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 16, 2015 |
| Est. completion date |
January 1, 2018 |
Study information
| Verified date |
May 2018 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This Study Was Made to Evaluate the Antibacterial Effect of Different Antibacterial
Combinations on Revascularization Process in Permanent Anterior Immature Teeth. Immature
Necrotic Permanent Maxillary Incisors (n = 40) of Patients 8-18 Years Old Were Divided Into 4
Equal Groups (Each n = 10) According to the Intracanal Medicament: Group 1 Was Treated With
Triple Antibiotic Paste (TAP), Group 2 Was Treated With Ciprofloxacin + Propolis Paste (CP),
Group 3 Was Treated With Ciprofloxacin + Metronidazole Paste (CM), Group 4 Was Treated With
Propolis + Metronidazole Paste (PM). Cases Were Followed at Regular Intervals up to 18 Months
Clinically and Radiographically.
Description:
Introduction In the last 10 years, numerous published cases and case series described the
revascularization or regenerative endodontics. Revascularization is a conservative method for
inducing maturogenesis in necrotic immature teeth. The favorable outcomes of regenerative
endodontics are largely dependent on the adequate disinfection of the root canal. These
canals with compromised fragile underdeveloped dentinal walls represent a contraindication
for mechanical instrumentation; thus, chemical debridement remains the main form of
disinfection. A mixture of ciprofloxacin, metronidazole, and minocycline, known as the triple
antibiotic paste (TAP), has been shown to be very effective in eliminating endodontic
pathogens in vitro and in situ. However, TAP has an adverse effect on stem cell survival.
Discoloration of the tooth is a problem mostly related to the use of minocycline in TAP.
Moreover, TAP can demineralize dentin resulting in reduced microhardness and fracture
resistance. Propolis, a flavonoid-rich resinous product of honeybees, is ten times less
cytotoxic than calcium hydroxide and has a well-known antibacterial effect. Therefore,
creating alternatives to the TAP for disinfecting the root canal of necrotic teeth during the
process of pulp revascularization is thought to be of value.
Materials and methods Forty patients with immature, nonvital maxillary incisors were included
in this study from the outpatient clinic of the Faculty of Dentistry, Ain Shams University,
Cairo, Egypt. A detailed medical and dental history was obtained from each patient's parents
or guardians. Only medically free patients were included in this research. The clinical and
radiographic exclusion criteria were teeth with vertical fractures, periodontally involved
teeth, and nonrestorable teeth. All procedures were performed after obtaining proper
institutional review board approval based on the regulations of the Ethical Committee of the
Faculty of Dentistry, Ain Shams University. Intraoral periapical radiographs revealed
immature apices. The age of the patients ranged between 8 and 18 years. Informed consent was
signed for each case by the patient's parents or guardians including the proposed treatment
and possible outcomes or complications.
Cases were divided randomly and equally into 4 groups according to the intracanal medicament
(10 patients for each group):
TAP group: was treated with Triple Antibiotic Paste CP group: was treated with Ciprofloxacin
+ Propolis paste CM group: was treated with Ciprofloxacin + Metronidazole paste PM group: was
treated with Propolis + Metronidazole paste
1. Triple Antibiotic Paste (TAP):
It consisted of Ciprofloxacin (Ciprocin 250 mg tablets; EPICO, Cairo, Egypt),
Metronidazole (Flagyl 500 mg tablets; Sanofi Aventis Pharma, Cairo, Egypt), Doxycycline
(Vibramycin 100 mg capsules; Pfizer, Cairo, Egypt). One Doxycycline capsule content was
evacuated in a sterile mortar, one tablet of metronidazole and one tablet of
ciprofloxacin were crushed and ground in the same mortar using a pestle into homogenous
powder. Saline drops (Otrivin baby saline; Novartis, Cairo, Egypt) were added and mixed
using the pestle until a creamy paste was achieved.
2. Ciprofloxacin + Propolis Paste:
Ethanol extract of raw propolis (EEP; ElEzaby Co. Labs, Cairo, Egypt.) was prepared by
adding 10 gm of propolis (Imtinan, Cairo, Egypt) to 40 gm of 70% ethanol (ElGomhorya
Co., Cairo, Egypt) (for 20% tincture) in a dark container to prevent reduction of
propolis. The container was sealed and placed at room temperature for a period of three
weeks. The sealed container was manually shaken every 2 days to ensure proper mixing.
After 3 weeks, the container was opened and ethanol extract of propolis was obtained.
Ethanol-free EEP was made by evaporating the ethanol in a water bath. EEP was then mixed
with Ciprofloxacin powder in the ratio 1:1. Saline drops were added and mixed using the
pestle until a creamy paste was achieved.
3. Ciprofloxacin + Metronidazole Paste:
Ciprofloxacin powder was mixed with Metronidazole powder in the ratio 1:1. Saline drops were
added and mixed using the pestle until a creamy paste was achieved.
4) Propolis + Metronidazole paste: EEP was mixed with Metronidazole powder in the ratio 1:1.
Saline drops were added and mixed using the pestle until a creamy paste was achieved.
A preoperative radiograph was taken using the standardized paralleling technique by the Rinn
XCP (Rinn Corporation Elgin, Illinois, USA) alignment system and Fona ScaNeo intra-oral
digital imaging system (FONA Dental, Bratislava, Slovak Republic). Patients were treated as
follows: Caries was excavated; access cavity was prepared. The rubber dam was then applied
and working length was determined with a periapical radiograph taken with a file inserted
into the canal. Canal space was debrided using K file size #80. Canal space was irrigated
using 40 cc of NaOCl 2.6% solution and final flush of saline. Canal space was dried using
paper points. The antibiotic paste was prepared as previously described. One cc of the
prepared paste was injected into the canals using a sterile plastic syringe with 20" gauge
needle. Care was taken to avoid apical extrusion and to minimize placement in the coronal
portion of the tooth. The access cavity was then sealed using temporary restoration (Coltosol
F; Coltene Whaledent, Altstatten, Switzerland) over plain cotton. After the 3 weeks, under
the same aseptic conditions, anesthesia without vasoconstrictor (Mepecaine, Alexandria Co.,
Alexandria, Egypt) was administrated. The tooth was re-entered, the antibiotic paste was
removed and the canal was irrigated using a sterile saline and dried using paper points.
Sterile hand file size #25 was introduced into the root canal and placed at 2 mm beyond the
working length to induce bleeding into the canal. The bleeding was allowed to reach a 3-mm
level below the cemento-enamel junction, and teeth were left at rest for 5 minutes so that a
blood clot could be formed. Next, a 3-mm plug of MTA (Angelus; Londrina, Brazil) was inserted
into the canals using a suitable-sized amalgam carrier to seal the root canal at the cervical
level. The MTA plug was verified radiographically. The MTA plug was then covered by moist
cotton and temporary filling. After one week, MTA setting was confirmed clinically, adhesive
composite resin (Z250 Restorative; 3M ESPE, St Paul, Minnesota, USA) was used to seal the
access cavity.
Evaluation:
Patients were recalled for follow up at 3, 6, 9, 12, and 18 months. Follow-up included the
clinical assessment of pain and/or swelling and standardized radiographic assessment, which
included the following:
1. An increase in root length
2. An increase in root thickness
3. A decrease in apical diameter
4. A change in periapical bone density All radiographic measures were collected by the same
investigator. All radiographic measurements were repeated after 1 week, and the mean of
the 2 sets was considered as the final value.
Increase in root length: A measuring scale was set in the Image-J software (Image-J v1.44, US
National Institutes of Health, Bethesda, MD) by measuring a known clinical dimension to its
radiographic dimension. The scale was calculated as number of measured pixels per mm length.
Root length was measured as a straight line from the cemento- enamel junction to the
radiographic apex of the tooth in millimeters. Pre and follow-up root lengths were measured
using Image-J analysis software. Difference in length was calculated. Percentage of increase
in length was calculated as follows: percentage of increase in length = [(postoperative
length - preoperative length) / preoperative length] X 100.
Increase in root thickness: Using the preset measurement scale, the level of the apical third
was determined and fixed from the cemento-enamel junction. The root thickness and the pulp
width were measured mesiodistally at this level in millimeters. Mesiodistal dentin thickness
was measured by subtraction of the pulp space from the whole root thickness. Pre and
follow-up root thicknesses were measured. Measurements were done pre and post operatively at
the same fixed level. Difference in dentin thickness was calculated. Percentage of increase
in dentin thickness was calculated as follows: percentage of increase in dentin thickness =
[(postoperative thickness - preoperative thickness) / preoperative thickness] X 100.
Decrease in apical diameter: Using the preset measurement scale, the mesiodistal diameter of
the apical foramen was measured in millimeters. Measurements were done pre and
postoperatively. Percentage of apical closure was calculated as follows: percentage of apical
closure = [(preoperative apical diameter - postoperative apical diameter) / preoperative
apical diameter] X 100.
Periapical bone density:
Periapical bone density was estimated using Image-J software as follows: periapical area was
located and analyzed for bone density. Average area density was measured in scale from 0
(black) to 255 (white) and recorded for each radiograph. The same area was then measured in
subsequent radiographs and average densities were recorded for the follow up radiographs. The
difference between densities was calculated between subsequent radiographs. Percentage of
change in density was calculated from the original pre-operative radiograph density as
follows: percentage of change in density = [(postoperative bone density - preoperative bone
density)/preoperative bone density] X 100.
Data were collected, tabulated and statistically analyzed using statistical analysis software
SPSS (Statistical Packages for the Social Sciences 19.0, IBM, Armonk, NY). Two-way analysis
of variance was performed. The Tukey post hoc test was used in case of significance.
