Regeneration of Pulp-Dentin Development in Teeth With Necrotic Pulps and Immature Roots

This is a multi-center randomized clinical trial designed to test whether a regenerative
endodontic procedure using tissue engineering principles (REGENDO), or a revascularization
(REVASC) endodontic procedure, when compared to the standard apexification treatment using
mineral trioxide aggregate barrier-MTA apexification (APEX), produces a significantly better
composite clinical outcome for the treatment of immature permanent teeth with pulpal
necrosis. This study will use an antibiotic mixture called Triple Antibiotic Paste (TAP),
consisting of ciprofloxacin, metronidazole and minocycline, in the tooth for disinfection of
the root canal in study arms REGENDO and REVASC. The FDA has issued an Investigational New
Drug (IND) number allowing use of the triple antibiotic mixture in this trial. Other dental
materials used in this study have already been FDA approved for use in humans to provide a
matrix for the promotion of tissue growth in the root canal space. The study will also
attempt to identify the type of bacteria within the root canal space and surrounding tissues
by analyzing a small sample collected on a cotton-tip applicator. This clinical trial hopes
to determine which of the three treatment methods helps the tooth to grow stronger and
survive for at least two years after treatment.

Inclusion Criteria:

- Age 6-20

- Participant has a permanent tooth with a necrotic pulp (as defined by lack of
responsiveness to both electrical pulp tests and cold [EndoIce] tests). If the tooth
was traumatized, then pulpal necrosis is defined as either: 1) no response to both
electrical pulp test and cold [EndoIce] test by three months after trauma, or 2)
presence of a periapical lesion, or 3) radiographic evidence of root resorption, or 4)
discoloration of the crown.

- Tooth in question is restorable (as defined by Class A or Class B using Samet and
Jotkowitz classification) without the need of a stainless steel crown.

- Incomplete (i.e., immature) root development defined by apical foramen ≥1.0mm (each
foramina >1.0mm for multi-rooted teeth).

- At least 5 mm of root development (CEJ to radiographic apex).

- Willing and able to provide informed assent/consent.

- Legal guardian willing and able to provide informed consent.

Exclusion Criteria:

- No access to telephone for study contacts.

- Unable to comprehend study materials in English or Spanish.

- Subject not available for follow up at 12 or 24 months.

- Previous allergic response to ciprofloxacin, metronidazole or minocycline or any
materials used in the study.

- History of systemic diseases with altered immune function including diabetes,
immunodeficiency, leukemia, Addison's or Cushing's disease.

- History of taking immunosuppressants or chemotherapeutic agents including
glucocorticoids in the past 3 months.

- Clinical or radiographic evidence of root fracture or alveolar fracture.

- Tooth in question received prior endodontic obturation.

- Tooth in question has class III mobility or dens invaginatus.

- Tooth in question has a history of avulsion with extra-oral dry time longer than 1
hour.

- Clinical judgement (with documentation of the reason)

- Radiographic or clinical identification of ankylosis (replacement resorption) or
inflammatory (infection-related) root resorption.