Evaluation of the effects of azithromycin and platelet-rich fibrin on wound healing after surgical removal of mandibular third molars

ISRCTN	ISRCTN36568405
DOI	https://doi.org/10.1186/ISRCTN36568405
Sponsor	Medical Faculty, University of Niš
Funder	University of Niš

Submission date: 20/05/2026
Registration date: 22/05/2026
Last edited: 21/05/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Oral Health

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Milan Spasić
Principal investigator

Blv. Dr Zorana Đinđića 52
Niš
18000
Serbia

Phone	+381638626663
Email	milan.spasic@medfak.ac.rs

Prof Milica Petrović
Scientific

Blv. Dr Zorana Đinđića 52
Niš
18000
Serbia

Phone	+381642373966
Email	milica.petrovic@medfak.ac.rs

Prof Milan Stojiljković
Scientific

Blv. Dr Zorana Đinđića 52
Niš
18000
Serbia

Phone	+3810184226216
Email	milan.stojiljkovic@medfak.ni.ac.rs

Prof Simona Stojanović
Public

Blv. Dr Zorana Đinđića 52
Niš
18000
Serbia

Phone	+381692245322
Email	simona.stojanovic@medfak.ac.rs

Prof Miloš Kostić
Scientific

Blv. Dr Zorana Đinđića 52
Niš
18000
Serbia

Phone	+3810184226216
Email	milos.kostic@medfak.ni.ac.rs

Prof Nikola Živković
Scientific

Blv. Dr Zorana Đinđića 52
Niš
18000
Serbia

Phone	+3810184226216
Email	nikola.zivkovic@medfak.ni.ac.rs

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Blinded (masking used)
Control	Active
Assignment	Crossover
Purpose	Health services research, Supportive care, Treatment
Scientific title	Cytomorphometric, immunological, and clinical analysis of the effects of azithromycin and platelet-rich fibrin on postoperative wound healing following surgical extraction of impacted mandibular third molars
Study acronym	APRIM Study
Study objectives	This study was conducted to evaluate the influence of azithromycin and platelet-rich fibrin (PRF) on postoperative inflammatory parameters and healing outcomes after extraction of impacted mandibular third molars, relative to routine treatment, by means of cytomorphometric, immunohistochemical, and clinical evaluations.
Ethics approval(s)	1. Approved 20/02/2024, Ethics committe, Medical Faculty, University of Niš (Blv. Dr Zorana Đinđića 81, Niš, 18000, Serbia; +381184226644; info@medfak.ni.ac.rs), ref: 12/1760-1/2-5 2. Approved 19/01/2024, Ethics committee, Clinics Of Dentistry Niš (Blv. Dr Zorana Đinđića 52, Niš, 18000, Serbia; +381184226216; stomatolog_nis@kzsnis.rs), ref: 14/1-2023-3/EO
Health condition(s) or problem(s) studied	Surgical extraction of impacted mandibular third molar
Intervention	Participants were randomly allocated into three study groups using computer-generated randomisation. Group assignments were placed in sequentially numbered, sealed opaque envelopes, which were opened at the time of intervention allocation. Intervention description Control group: Participants received standard postoperative therapy consisting of oral amoxicillin 500 mg every 8 hours for 5 days following surgical extraction of vertically impacted mandibular third molars (standard protocol). PRF group: Following extraction and socket debridement, platelet-rich fibrin (PRF) prepared from autologous venous blood was placed into the extraction socket. Participants additionally received standard postoperative oral amoxicillin therapy (500 mg every 8 hours for 5 days). PRF + azithromycin group: Participants received a single prophylactic oral dose of azithromycin (1 g) one day before surgery. Following extraction and socket debridement, PRF prepared from autologous venous blood was placed into the extraction socket. Standard postoperative oral amoxicillin therapy (500 mg every 8 hours for 5 days) was also administered. PRF preparation protocol: Twenty millilitres of venous blood were collected into sterile tubes without anticoagulant and centrifuged at 1300 rpm (200 × g) for 14 minutes using a fixed-angle rotor centrifuge. The PRF clot was isolated and placed into the extraction socket within 15 minutes after centrifugation.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Cytomorphometric changes (area, IntDen, AR, StdDev, Min, Max, Perim, Circ, FeretX, FeretY, and roundness) measured using exfoliative cytology with Papanicolaou staining and ImageJ morphometric analysis at baseline and postoperative day 7 Immunologic observation in cervical fluid samples measured using an ELISA at preoperative and postoperative Microbiological findings measured using PCR analysis at preoperative and postoperative
Key secondary outcome measure(s)	Postoperative pain measured using a Visual Analogue Scale (VAS) at postoperative days 3 and 7 Postoperative edema, assessed via standardized facial reference point distances (tragus–gonion and tragus–oral commissure) measured using manual linear measurements with a flexible measuring tape at baseline and postoperative day 7 Wound healing measured using the Landry Healing Index at postoperative days 3, 7, and 14
Completion date	03/02/2026

Eligibility

Participant type(s)
Age group	Adult
Lower age limit	18 Years
Upper age limit	50 Years
Sex	All
Target sample size at registration	90
Total final enrolment	124
Key inclusion criteria	Vertically impacted third molars that are radiographically diagnosed according to Winter’s classification
Key exclusion criteria	1. Allergies to penicillin or lidocaine 2. Chronic systemic diseases 3. Cystic lesions 4. Infections around the impacted third molar, odontomas, or syndromes affecting the orofacial region
Date of first enrolment	03/04/2024
Date of final enrolment	29/09/2025

Locations

Countries of recruitment

Serbia

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other files			21/05/2026	No	No
Statistical Analysis Plan			21/05/2026	No	No

Additional files

49568_Informed Consent Form.pdf: Other files
49568_SAP.pdf: Statistical Analysis Plan

Editorial Notes

21/05/2026: Study’s existence confirmed by the Ethics committee, Clinics Of Dentistry Niš, Serbia.