Antibiotic Prophylaxis After Simple Tooth Extraction in Immunosuppressed Patients With Autoimmune Rheumatic Diseases (PRO-EXOD)

Effectiveness of Short-Course Antibiotic Prophylaxis After Simple Tooth Extraction in Immunosuppressed Patients With Autoimmune Rheumatic Diseases

This randomized, double-blind, placebo-controlled clinical trial aims to evaluate whether single-dose amoxicillin prophylaxis administered prior to simple tooth extraction reduces postoperative infection rates in immunosuppressed patients with autoimmune rheumatic diseases (ARDs).

Although antibiotic prophylaxis is not recommended for healthy individuals undergoing simple extractions, immunosuppressed ARD patients frequently receive antibiotics despite limited evidence supporting this practice.

Secondary objectives include assessing infection severity, postoperative complications, and the impact of ARD diagnosis and immunosuppressive treatment on infection risk.

Study Overview

• Status: Not yet recruiting
• Conditions: Tooth Extraction; Antibiotic Prophylaxis; Infection Prevention; Autoimmune Rheumatic Diseases
• Intervention / Treatment: Drug: Amoxicillin; Other: Placebo

Detailed Description

Simple tooth extractions are common procedures, and postoperative infection rates are low in the general population. Current guidelines discourage prophylactic antibiotic use to reduce microbial resistance, adverse reactions, and microbiome disruption.

However, immunosuppressed patients with ARDs often receive prophylaxis due to theoretical risks of delayed healing and increased susceptibility to infection. Evidence in other immuno-compromised populations suggests that simple extractions may be safe without antibiotics, but no prospective trials have evaluated this issue specifically in ARD patients.

This study is the first prospective, randomized, double-blind, placebo-controlled trial designed to determine whether antibiotic prophylaxis is necessary in this population.

• Study Type: Interventional
• Enrollment (Estimated): 352
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eloisa Bonfá, Full Professor; Phone Number: +55 11 30617492; Email: eloisa.bonfa@hc.fm.usp.br
• Study Contact Backup: Name: Luciana PC Seguro, PhD; Phone Number: +55 11 999916381; Email: luciana.seguro@hc.fm.usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Confirmed diagnosis of an ARD: SLE, RA, JIA, AS, PsA, IIM, systemic vasculitis, primary Sjögren's syndrome, or SSc
• Under immunosuppressive or biologic therapy ≥3 months
• Indication for simple extraction of tooth with chronic odontogenic focus
• Provided informed consent

Exclusion Criteria:

• Individuals who do not agree to participate in the study will be excluded.
• Patients who require more technically complex extractions, such as impacted or impacted third molars.
• Patients with local and systemic changes that require more extensive antibiotic coverage, such as cases with clinical signs of acute infections, anticoagulated patients, heart patients, patients who have undergone radiotherapy or are undergoing treatment for neoplasms.
• Patients allergic to amoxicillin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1 - Antibiotic Prophylaxis; Single 2 g oral dose administered 30-60 minutes before tooth extraction	Drug: Amoxicillin; Amoxicillin 2 g a single prophylactic dose prior to simple extraction.
Placebo Comparator: Arm 2 - No Antibiotic Prophylaxis; Four matching placebo tablets administered 30-60 minutes before extraction	Other: Placebo; Matching placebo tablets administered as a single dose prior to extraction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of postoperative infections	Proportion of participants developing postoperative infection, defined as purulent/serous exudate, fever (>37.8°C), or clinical signs of local infection.	7 days post-extraction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity and Duration of Infection	Presence and duration of purulent/serous exudate, fever (>37.8°C), or clinical signs of local infection and systemic symptoms	7 days
Incidence of Postoperative Complications	Presence of alveolitis, fever, edema, erythema, trismus, exudate, and pain	7 days
Influence of ARD Diagnosis and Immunosuppressive Regimen	Infection rate and severity related to ARD Diagnosis and Immunosuppressive Regimen	7 days
Disease Activity Flares	Disease Activity Flares according to specific ARD definitions of exacerbation, as follows: Systemic Lupus Erythematosus(SLE): Increase >3 points in SLE Disease Activity Index 2000(SLEDAI-2K) Rheumatoid Arthritis(RA): Increase in Disease Activity Score-C-reactive protein(DAS28-CRP)>1.2, or >0.6 if baseline DAS28-CRP>3.2 Juvenile Idiopathic Arthritis(JIA): Increase in JIA Disease Activity Score(JADAS-27) >5 points, or worsening ≥2 active joints Ankylosing Spondylitis(AS): Increase in AS Disease Activity Score(ASDAS) >0.9. Psoriatic Arthritis(PsA): Worsening in Disease Activity Index for PsA(DAPSA) Systemic Vasculitis: Increase in Birmingham Vasculitis Activity Score(BVAS). Primary Sjögren's Syndrome: EULAR Sjögren's Syndrome Disease Activity Index(ESSDAI) Systemic Sclerosis (SSc): Increase in modified Rodnan skin score, new digital ulcers, worsening dyspnea, or increase in EULAR Systemic Sclerosis Impact of Disease Index (ScleroID) Inflammatory Myopathies (IIM): muscle weakness, CK	Day 1 through Day 30

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Eloisa Bonfá, Full Professor, Hospital das Clínicas da Faculdade de Medicina da USP - HCFMUSP

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Amoxicillin; Antibiotic Stewardship; Tooth Extraction; Infection Prevention; Autoimmune Rheumatic Diseases
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Penicillin G; beta-Lactams; Lactams; Ampicillin; Penicillins; Amoxicillin
• Other Study ID Numbers: 69108723.1.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No