## Protocol Section
### Identification Module
**NCT ID:** NCT06422221

**Brief Title:** An Oral Doxycycline Regimen to Prevent Bacteremia Following Dental Procedures

**Official Title:** An Oral Doxycycline Regimen to Prevent Bacteremia Following Dental Procedures

#### Organization Study ID Info
**ID:** Doxycycline Regimen
#### Organization
**Class:** OTHER
**Full Name:** University of Santiago de Compostela
### Status Module
#### Completion Date
**Date:** 2025-06-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-18

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-01-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-14

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-18
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Hospital Clinico Universitario de Santiago

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Santiago de Compostela

#### Responsible Party

**Investigator Affiliation:** University of Santiago de Compostela

**Investigator Full Name:** Pedro DIz DIos

**Investigator Title:** Full Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Although controversy exists regarding the efficacy of antibiotic prophylaxis for patients at risk of infective endocarditis, expert committees continue to publish recommendations for antibiotic prophylactic regimens. The last American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines include several important changes, highlighting that clindamycin (CLI) is no longer recommended as an alternative to amoxicillin in those allergic to penicillin. This new project aims to evaluate the effectiveness of oral doxycycline in preventing post-dental extraction bloodstream infection.

**Detailed Description:** PURPOSE: Despite the controversy about the risk of developing bacterial endocarditis of oral origin, numerous Expert Committees in different countries continue to publish prophylactic regimens. To date, the literature is unclear about the role of antimicrobial prophylaxis in the prevention of bacteremia following dental procedures. The aim of this study is to evaluate the efficacy of prophylactic dosage with oral doxycycline (DXC) in the prevention of bacteremia following dental extractions.

SELECTION OF THE STUDY GROUP AND STUDY DESIGN: The study group will comprise patients who, for behavioral reasons (autism, learning disabilities, phobias, etc.), will undergo dental extractions under general anesthesia in the Santiago de Compostela University Hospital (Santiago de Compostela, Spain). 150 patients will be selected and will be randomly distributed into 3 study groups: control group (receiving no prophylaxis), CLI group (receiving 600 mg oral CLI) and DXC group (receiving 100 mg oral DXC).

COLLECTION OF SAMPLES FOR BLOOD CULTURE: To determine the prevalence of bacteremia, a peripheral venous blood sample (10 ml) will be drawn from each patient. Samples will be inoculated in BACTEC plus (Becton Dickinson and Company, Sparks, MD) aerobic and anaerobic blood culture bottles, and will be processed in the Bactec 9240 (Becton Dickinson).

MICROBIOLOGICAL ANALYSIS OF BLOOD CULTURES: A Gram stain will be performed on each positive blood culture. The positive blood cultures in the aerobic media will be subcultured on blood agar and chocolate agar in an atmosphere of 5 to 10% carbon monoxide and on MacConkey agar under aerobic conditions. The same protocol will be used for the positive blood cultures in the anaerobic media, with subculture on Schaedler agar and incubation in an anaerobic atmosphere. The bacteria isolated will be identified by using the battery of biochemical tests provided with the Vitek system for Gram-positive bacteria, Neisseria spp., Haemophilus spp., and obligate anaerobic bacteria. The viridans group streptococci will be classified into five groups, the Streptococcus mitis, S. anginosus, S. salivarius, S. mutans, and S. bovis groups, by applying the Ruoff criteria. Facklam's criteria will be used to identify unusual Streptococcus spp. and other Gram-positive cocci in chains.

The subculture and further identification of the isolated bacteria will be performed by conventional microbiological techniques. The collection, handling, and transport of the blood samples for blood culture will be performed according to the recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology.

### Conditions Module

**Conditions:**

- Bacteremia

- Endocarditis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Masking Description:** Single

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 150

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Receiving no prophylaxis

**Label:** No Intervention

**Type:** NO_INTERVENTION

#### Arm Group 2

**Description:** Receiving 600 mg oral Clindamycin 1 hour before general anesthesia and before any dental manipulation

**Intervention Names:**

- Drug: Clindamycin

**Label:** Clindamycin

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** Receiving 100 mg oral Doxycycline 1 hour before general anesthesia and before any dental manipulation

**Intervention Names:**

- Drug: Doxycycline

**Label:** Doxycycline

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Clindamycin

**Description:** Receiving 600 mg oral Clindamycin 1 hour before general anesthesia and before any dental manipulation

**Name:** Clindamycin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Doxycycline

**Description:** Receiving 100 mg oral Doxycycline 1 hour before general anesthesia and before any dental manipulation

**Name:** Doxycycline

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Positive cultures

**Measure:** Bacteremia in participants receiving a prophylactic dosage with oral doxycyclin

**Time Frame:** Changes from baseline in prevalence of bacteremia at 30 seconds and 15 minutes after the final dental extraction

#### Secondary Outcomes

**Description:** Positive cultures

**Measure:** Bacteremia in participants receiving a prophylactic dosage with oral clindamycin

**Time Frame:** Changes from baseline in prevalence of bacteremia at 30 seconds and 15 minutes after the final dental extraction

**Description:** Positive cultures

**Measure:** Bacteremia in participants receiving no prophylaxis

**Time Frame:** Changes from baseline in prevalence of bacteremia at 30 seconds and 15 minutes after the final dental extraction

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subjects must have at least 10 teeth.
* Subjects must have the need for a dental extraction under general anesthesia (for behavioral reasons).
* Subjects will be recruited regardless of the extent and severity of their dental and/or periodontal disease.

Exclusion Criteria:

* Age under 18 years
* Body weight under 40 kg
* Receipt of antibiotics in the previous 3 months
* Routine use of oral antiseptics
* A history of allergy or intolerance to doxycycline
* A history of allergy or intolerance to cindamycin
* Any type of congenital or acquired immunodeficiency
* Any known risk factor for bacterial endocarditis
* Any known risk factor for prolonged bleeding

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** javier.fernandez@usc.es

**Name:** JAVIER Feijoo

**Phone:** +34636962202

**Role:** CONTACT

**Contact 2:**

**Email:** pedro.diz@usc.es

**Name:** Pedro Diz Dios

**Phone:** +34617864293

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Santiago De Compostela

**Contacts:**

***Contact 1:***

- **Email:** javier.fernandez@usc.es

- **Name:** Javier Fernandez Feijoo

- **Role:** CONTACT

***Contact 2:***

- **Email:** pedro.diz@usc.es

- **Name:** Pedro Diz Dios

- **Role:** CONTACT

**Country:** Spain

**Facility:** Santiago de Compostela University Hospital

**State:** A Coruña

**Zip:** 15782

#### Overall Officials

**Official 1:**

**Affiliation:** Santiago de Compostela University

**Name:** Pedro Diz Dios

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** On request

**Description:** IPD will be available on request

**Info Types:**

- CSR

**IPD Sharing:** YES

**Time Frame:** By the end of the study (for 1 year)

### References Module

#### References

**Citation:** Diz Dios P. Infective endocarditis prophylaxis. Oral Dis. 2014 May;20(4):325-8. doi: 10.1111/odi.12221. Epub 2014 Jan 13.

**PMID:** 24373017

**Citation:** Valdes C, Tomas I, Alvarez M, Limeres J, Medina J, Diz P. The incidence of bacteraemia associated with tracheal intubation. Anaesthesia. 2008 Jun;63(6):588-92. doi: 10.1111/j.1365-2044.2008.05449.x.

**PMID:** 18477269

**Citation:** Pineiro A, Tomas I, Blanco J, Alvarez M, Seoane J, Diz P. Bacteraemia following dental implants' placement. Clin Oral Implants Res. 2010 Sep;21(9):913-8. doi: 10.1111/j.1600-0501.2010.01928.x.

**PMID:** 20701619

**Citation:** Diz Dios P, Tomas Carmona I, Limeres Posse J, Medina Henriquez J, Fernandez Feijoo J, Alvarez Fernandez M. Comparative efficacies of amoxicillin, clindamycin, and moxifloxacin in prevention of bacteremia following dental extractions. Antimicrob Agents Chemother. 2006 Sep;50(9):2996-3002. doi: 10.1128/AAC.01550-05.

**PMID:** 16940094

**Citation:** Limeres Posse J, Alvarez Fernandez M, Fernandez Feijoo J, Medina Henriquez J, Lockhart PB, Chu VH, Diz Dios P. Intravenous amoxicillin/clavulanate for the prevention of bacteraemia following dental procedures: a randomized clinical trial. J Antimicrob Chemother. 2016 Jul;71(7):2022-30. doi: 10.1093/jac/dkw081. Epub 2016 Mar 29.

**PMID:** 27029851

**Citation:** Relvas M, Diz P, Seoane J, Tomas I. Oral Health Scales: design of an oral health scale of infectious potential. Med Oral Patol Oral Cir Bucal. 2013 Jul 1;18(4):e664-70. doi: 10.4317/medoral.18427.

**PMID:** 23524418

**Citation:** Martins CC, Lockhart PB, Firmino RT, Kilmartin C, Cahill TJ, Dayer M, Occhi-Alexandre IGP, Lai H, Ge L, Thornhill MH. Bacteremia following different oral procedures: Systematic review and meta-analysis. Oral Dis. 2024 Apr;30(3):846-854. doi: 10.1111/odi.14531. Epub 2023 Mar 29.

**PMID:** 36750413

**Citation:** Thornhill MH, Gibson TB, Yoon F, Dayer MJ, Prendergast BD, Lockhart PB, O'Gara PT, Baddour LM. Endocarditis, invasive dental procedures, and antibiotic prophylaxis efficacy in US Medicaid patients. Oral Dis. 2024 Apr;30(3):1591-1605. doi: 10.1111/odi.14585. Epub 2023 Apr 27.

**PMID:** 37103475

**Citation:** Diniz Freitas M, Alvarez Fernandez M, Vasallo Vidal FJ, Limeres Posse J, Diz Dios P, Fernandez Feijoo J. Oral amoxicillin/clavulanate for the prevention of bacteremia following dental extractions. Oral Dis. 2023 Jul;29(5):2272-2276. doi: 10.1111/odi.14221. Epub 2022 May 13.

**PMID:** 35467064

**Citation:** Dayer MJ, Jones S, Prendergast B, Baddour LM, Lockhart PB, Thornhill MH. Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis. Lancet. 2015 Mar 28;385(9974):1219-28. doi: 10.1016/S0140-6736(14)62007-9. Epub 2014 Nov 18.

**PMID:** 25467569

**Citation:** Lean SSH, Jou E, Ho JSY, Jou EGL. Prophylactic antibiotic use for infective endocarditis: a systematic review and meta-analysis. BMJ Open. 2023 Aug 22;13(8):e077026. doi: 10.1136/bmjopen-2023-077026.

**PMID:** 37607797

**Citation:** Dayer MJ, Thornhill M, Baddour LM. Antibiotic prophylaxis for patients at risk of infective endocarditis: an increasing evidence base? Br J Cardiol. 2023 Feb 21;30(1):6. doi: 10.5837/bjc.2023.006. eCollection 2023.

**PMID:** 37705833

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

- ID: D000007239

- Term: Infections

- ID: D000018805

- Term: Sepsis

- ID: D000018746

- Term: Systemic Inflammatory Response Syndrome

- ID: D000007249

- Term: Inflammation

- ID: D000010335

- Term: Pathologic Processes

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC01

- Name: Infections

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M7858

- Name: Endocarditis

- Relevance: HIGH

- As Found: Endocarditis

- ID: M18877

- Name: Bacteremia

- Relevance: HIGH

- As Found: Bacteremia

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M20864

- Name: Sepsis

- Relevance: LOW

- As Found: Unknown

- ID: M16869

- Name: Toxemia

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M20818

- Name: Systemic Inflammatory Response Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M10293

- Name: Inflammation

- Relevance: LOW

- As Found: Unknown

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000016470

- Term: Bacteremia

- ID: D000004696

- Term: Endocarditis

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000000962

- Term: Antimalarials

- ID: D000000981

- Term: Antiprotozoal Agents

- ID: D000000977

- Term: Antiparasitic Agents

- ID: D000011500

- Term: Protein Synthesis Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

- ID: M7493

- Name: Doxycycline

- Relevance: HIGH

- As Found: Open-Label Study

- ID: M6214

- Name: Clindamycin

- Relevance: HIGH

- As Found: Currently

- ID: M220697

- Name: Clindamycin palmitate

- Relevance: HIGH

- As Found: Currently

- ID: M231711

- Name: Clindamycin phosphate

- Relevance: HIGH

- As Found: Currently

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4280

- Name: Antimalarials

- Relevance: LOW

- As Found: Unknown

- ID: M4298

- Name: Antiprotozoal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4294

- Name: Antiparasitic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000004318

- Term: Doxycycline

- ID: D000002981

- Term: Clindamycin

- ID: C000000489

- Term: Clindamycin palmitate

- ID: C000007084

- Term: Clindamycin phosphate

### Misc Info Module

- Version Holder: 2024-05-31
