Application of Advanced Platelet-Rich Fibrin Plus (A-PRF+) in Revascularisation of Necrotic Immature Permanent Teeth

Not Applicable

Completed

• Conditions: Root Maturation; Necrotic Immature Permanent Teeth; Regenerative Endodontic Treatment; Pulp Regeneration; Periapical Lesions

• Registration Number: NCT07092488
• Lead Sponsor: University of Zagreb

Brief Summary

The goal of this clinical trial is to evaluate the effectiveness of an advanced platelet-rich fibrin plus (A-PRF+) revascularization procedure to promote healing and root development in necrotic immature permanent single-rooted teeth in children and adolescents aged 8 to 18 years.

The main questions it aims to answer are:

* Does the A-PRF+ protocol improve root length, dentinal wall thickness, and apical closure compared to traditional calcium hydroxide apexification treatment?

* Does A-PRF+ promote restoration of pulp vitality and reduce clinical symptoms such as pain, inflammation, or tooth discoloration? Results from the A-PRF+ treatment group will be compared with those from a historical control group receiving traditional calcium hydroxide apexification to evaluate relative effectiveness.

Participants will:

* Receive treatment following the A-PRF+ protocol, which includes disinfecting the tooth canal, applying an autologous platelet-rich fibrin scaffold, and sealing with glass ionomer cement;

* Undergo clinical and radiographic follow-up visits at 1, 3, 6, 9, and 12 months;

* Have pulp vitality tested with cold, electric, and laser Doppler flowmetry methods;

* Be monitored for clinical symptoms, healing progress, and restoration performance.

This study will help determine whether A-PRF+ is a safe and effective alternative to conventional apexification for regenerating necrotic immature teeth in young patients.

Detailed Description

This study is a prospective interventional clinical trial evaluating an advanced platelet-rich fibrin plus (A-PRF+) revascularization protocol compared to a historical control group treated with traditional calcium hydroxide apexification for necrotic immature permanent single-rooted teeth in children and adolescents aged 8 to 18 years.

The main goal is to assess the regenerative effectiveness of the A-PRF+ protocol in promoting root development, including root lengthening, dentinal wall thickening, and apical closure, compared to conventional apexification. Secondary objectives include evaluating pulp vitality restoration and monitoring clinical outcomes such as symptom resolution, tooth survival, and adverse effects like tooth discoloration.

Participants in the experimental group were prospectively enrolled and received treatment involving minimal mechanical instrumentation, canal disinfection with sodium hypochlorite, intracanal calcium hydroxide medicament, followed by triple antibiotic paste. At the final appointment, autologous A-PRF+ was prepared from peripheral blood and applied as an intracanal scaffold extending into the coronal cavity, sealed permanently with glass ionomer cement.

The control group consists of patients previously treated at the same institution with calcium hydroxide apexification. Their clinical and radiographic records were retrospectively reviewed for comparison. Apexification was not performed as part of this study.

Clinical and radiographic follow-ups were conducted at 1, 3, 6, 9, and 12 months, including pulp vitality testing with cold, electric, and laser Doppler flowmetry methods, along with standardized periapical radiographs to measure root length, dentinal wall thickness, and apical diameter. Restoration quality was assessed using modified USPHS criteria.

This study aims to determine if the A-PRF+ protocol provides a safe and effective regenerative alternative to traditional apexification for treating necrotic immature teeth, potentially enhancing long-term tooth preservation in pediatric patients.

Study Timeline

• Study Start: 2018-03-19
• Primary Completion: 2021-04-14
• Study Completion: 2021-06-18
• Status Verified: 2025-07
• Study First Submitted: 2025-07-21
• Study First Submitted QC: 2025-07-21
• Last Update Submitted: 2025-07-21
• Study First Posted: 2025-07-30
• Last Update Posted: 2025-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Patients aged 8 to 18 years presenting with immature permanent single-rooted teeth with necrotic pulp caused by caries or dental trauma
• Preserved tooth crown
• Negative response to cold and electric pulp tests
• Radiographic evidence of incomplete root development (Cvek stages I-IV)
• Apical diameter greater than 0.5 mm

Exclusion Criteria

• Presence of systemic illness or allergies to treatment components
• Complicated crown or root fractures
• Evidence of ankylosis or root resorption
• Ongoing orthodontic treatment
• Inability to comply with follow-up appointments (e.g., needle phobia or poor cooperation)
• Subsequent trauma to the treated tooth during the study period
• Missed recall appointments

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Apical Closure	From enrollment through 12 months post-treatment	Apical closure was assessed by measuring the reduction in apical diameter on standardized periapical radiographs. Radiographs were consistently acquired using a film holder to minimize angulation differences and distortion. Two independent blinded examiners used diagnostic software with 0.1 mm precision to measure the distance across the apical foramen. Changes from baseline to follow-up at 12 months were used to quantify apical closure.
Root Lengthening	From enrollment through 12 months post-treatment	Root lengthening was assessed by measuring the linear distance from the cementoenamel junction (CEJ) to the radiographic apex on standardized periapical radiographs. Radiographs were obtained using a film holder to ensure consistent angulation and minimize distortion. Measurements were performed using diagnostic software with a precision of 0.1 mm by two independent blinded examiners. The change from baseline to follow-up measurements over the 12-month period was calculated to quantify root lengthening.
Dentinal Wall Thickening	From enrollment through 12 months post-treatment	Dentinal wall thickening was evaluated by measuring the increase in dentinal wall width at the coronal two-thirds of the root on standardized periapical radiographs. Radiographs were obtained using a film holder to ensure reproducible angulation and reduce distortion. Two blinded examiners independently performed measurements using diagnostic software with an accuracy of 0.1 mm. The difference between baseline and follow-up measurements over 12 months quantified dentinal wall thickening.

Secondary Outcome Measures

Name	Time	Method
Pulp Vitality Responses	From enrollment through 12 months post-treatment	Pulp vitality was assessed at each follow-up visit using cold testing and electric pulp testing on the treated tooth and contralateral control tooth. Laser Doppler flowmetry was performed once per patient at either the 9- or 12-month recall to quantitatively measure pulpal blood flow, indicating revascularization. All tests were performed by clinicians blinded to treatment allocation, with responses recorded as positive or negative.
Presence of Periapical Pathology	From enrollment through 12 months post-treatment	Presence or absence of periapical lesions was evaluated on standardized periapical radiographs at baseline and follow-up visits. Two blinded examiners independently assessed images for periapical pathology. Changes in lesion presence were recorded throughout the 12-month follow-up.
Clinical Evaluation of Restorations Using Modified USPHS Criteria	From enrollment through 12 months post-treatment	Clinical performance of glass ionomer cement restorations was assessed at each recall visit using Modified United States Public Health Service (USPHS) criteria. Parameters evaluated included retention, marginal discoloration, anatomic form, marginal adaptation, secondary caries, and surface texture. Each parameter was scored as Alpha (clinically excellent), Bravo (clinically acceptable), or Charlie (clinically unacceptable/failure).
Tooth Survival	From enrollment through 12 months post-treatment	Tooth survival was defined as retention of the treated tooth throughout the 12-month follow-up period. Any tooth loss or extraction was recorded as an event. Survival status was assessed during clinical recall visits.

Trial Locations

Locations (1)

Department of Pediatric and Preventive Dentistry, University Hospital Centre Zagreb; 🇭🇷 Zagreb, Croatia