NCT02541032

Brief Summary

The PREMIERS study is a proposal for conducting an adequately powered two center phase III randomized controlled trial to test whether intensive periodontal treatment reduces the risk of recurrent vascular events among ischemic stroke and TIA survivors. The study uses the resources in both states including established dental centers, Joint Commission Certified Stroke Centers, the Schools of Public Health, and the Institute for Partnerships to Eliminate Health Disparities. The proposal addresses specific issues with regards to recruitment of African-American and rural stroke/TIA patients advocating the use of culturally appropriate strategies to educate the study subjects regarding stroke, periodontal disease and the periodontal stroke link. The study proposes to utilize economic evaluation of the periodontal intervention from the budgetary perspective. The focus will be on the financial sustainability of providing aggressive periodontal therapy (with certain, although relatively low expenditures) in exchange for a reduction of uncertain recurrent vascular events that may require high cost emergency department utilization and/or inpatient care. The sustainability of the proposed intervention after the completion of the project is integrally linked to the health economic assessment to show the health care cost savings. By integration with a rural primary care center, with an African American majority and households with average incomes below the state average, the study ensures that the proposed intervention to reduce stroke disparity is applicable to this target population.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
400

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Dec 2015

Typical duration for phase_3

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 6, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 4, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

December 1, 2015

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2020

Completed
Last Updated

April 18, 2019

Status Verified

April 1, 2019

Enrollment Period

3.5 years

First QC Date

July 6, 2015

Last Update Submit

April 16, 2019

Conditions

Outcome Measures

Primary Outcomes (4)

  • Ischemic Stroke

    One year

  • Transient ischemic attack (TIA)

    One Year

  • Myocardial infarction (MI)

    One Year

  • Cardiovascular Death

    One Year

Secondary Outcomes (6)

  • Progression of Atherosclerosis

    One Year

  • Vascular Cognitive Impairment

    One Year

  • Blood Pressure

    One Year

  • hs-CRP

    One Year

  • hemoglobin A1c

    One Year

  • +1 more secondary outcomes

Study Arms (2)

Intensive Dental Treatment

ACTIVE COMPARATOR

Patients will undergo up to five sessions of full-mouth removal of subgingival dental plaque by the use of scaling and root planning under local anesthesia. Any hopeless teeth will be extracted during this treatment period, which will be as short as possible, but will extend to no more than 4 weeks. In addition to standard scaling and root planning, the investigators seek to better suppress the oral biofilm by administering Arestin locally into the periodontal pockets ≥6 mm. All patients will be reexamined at 3, 6 and 9 months for safety checks. Patients will be given instructions in basic oral hygiene and treated for stroke risk factors in accordance to the current guidelines for secondary stroke prevention.

Procedure: Intensive dental treatmentDrug: Arestin

Standard Dental Treatment

ACTIVE COMPARATOR

Patients will undergo supragingival mechanical scaling and polishing. They will be informed of the presence and severity of their periodontal disease and will be advised to be seen by their dentist if their condition requires immediate attention. If they have no dental provider they will be referred for care. All patients will be reexamined at 3, 6 and 9 months for safety checks. Among the group the periodontal condition will be monitored to assure there is no progression of disease. If any site demonstrates an increase in periodontal pockets \>3mm, they will receive site-directed scaling and root planing. Patients will be given instructions in basic oral hygiene and treated for stroke risk factors in accordance to the current guidelines for secondary stroke prevention. At the completion of the study, the control treatment patients will be offered to receive the same dental care as provided to the intensive treatment group as needed.

Procedure: Standard dental treatment

Interventions

Up to five sessions of full-mouth removal of subgingival dental plaque by the use of scaling and root planning under local anesthesia. Any hopeless teeth will be extracted during this treatment period, which will be as short as possible, but will extend to no more than 4 weeks. In addition to standard scaling and root planning, the investigators seek to better suppress the oral biofilm by administering Arestin locally into the periodontal pockets ≥6 mm.

Also known as: Scaling, Planing, Hand Scaler, Ultrasonic Scaler
Intensive Dental Treatment

Supragingival mechanical scaling and polishing.

Also known as: Scaling, Polishing, Hand Scaler
Standard Dental Treatment

To better suppress the oral biofilm by administering Arestin locally into the periodontal pockets ≥6 mm.

Also known as: Minocycline Hydrochloride
Intensive Dental Treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient is at least 18 years of age with no upper age limit
  • Patient is able to consent, follow an outpatient protocol, and is available by telephone
  • Non-severely disabling initial stroke (modified Rankin score ≤ 3) or TIA in the past 90 days
  • Evaluable for periodontal examination and treatment (≥ 5 teeth) and able to sustain a dental examination
  • Contain ≥ 2 interproximal sites with ≥ 4 mm of clinical attachment loss (CAL) (initial periodontitis as defined by the Centers for Disease Control (CDC) Working Group on Surveillance Systems for Periodontal Infections - see below)

You may not qualify if:

  • Stroke due to intracranial hemorrhage, dissection, veno-occlusive disease, drugs, trauma, or vasculitis
  • Previous neurological impairment that would make detection of a subsequent event difficult
  • Co-morbid conditions that may limit survival to less than one year
  • Brain CT or MRI which shows a lesion other than stroke as the cause of the syndrome
  • History of medical conditions requiring antibiotic prophylaxis prior to dental exam (artificial cardiac valves, previous inflammation of the heart or valves, complex heart conditions or other heart malformations since birth, surgically constructed systemic pulmonary shunts, valvular dysfunctions, prolapse, hypertrophic cardiomyopathy, first two years of joint replacement, previous infections from artificial joint, any chronic or radiation-induced condition leading to immunosuppression or hemophilia)
  • Patients on oral anticoagulant therapy with a Prothrombin Time International Normalized Ratio (PT-INR) greater than 3.5 (may be corrected and enrolled).
  • Pregnancy confirmed by urine pregnancy test in women of child-bearing potential (≤ 55 years age)
  • Known allergy or hypersensitivity to local anesthesia or minocycline that cannot be medically managed
  • Participation in another randomized clinical trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

University of South Carolina School of Medicine Department of Neurology

Columbia, South Carolina, 29203, United States

RECRUITING

Related Publications (1)

  • Pikel K, Logue L, Verkuilen H, Wood S, Fritts A, Mintzer J, Bonilha L, Sethi P, Beckwith A, Huang D, Sen S. Determinants of post-stroke cognitive impairment in patients with periodontal disease. J Stroke Cerebrovasc Dis. 2025 Jul;34(7):108327. doi: 10.1016/j.jstrokecerebrovasdis.2025.108327. Epub 2025 Apr 22.

MeSH Terms

Conditions

Periodontal DiseasesStroke

Interventions

Tooth ExfoliationAircraftMinocycline

Condition Hierarchy (Ancestors)

Mouth DiseasesStomatognathic DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dental Physiological PhenomenaDigestive System and Oral Physiological PhenomenaAviationTransportationTechnology, Industry, and AgricultureTetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Souvik Sen, MD

    University of South Carolina

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel L Christmus

CONTACT

Kolby T Redd, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Chair, Department of Neurology

Study Record Dates

First Submitted

July 6, 2015

First Posted

September 4, 2015

Study Start

December 1, 2015

Primary Completion

June 1, 2019

Study Completion

June 1, 2020

Last Updated

April 18, 2019

Record last verified: 2019-04

Locations