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BacteremiaPhase 4NCT02150031

Bacteraemia Secondary to Tooth Extraction: Chlorhexidine Prophylaxis Protocols

A Phase 4 study testing 0.2% Chlorhexidine, 1% Chlorhexidine and Blood extraction in people with Bacteremia and Tooth Extraction Status Nos, run by University of Santiago de Compostela at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The first time the American Heart Association (AHA) suggested that disinfection of the gingival sulcus be performed as a complement to antibiotic prophylaxis in patients considered to be at risk of Infective endocarditis (IE) was in their protocol for the prevention of IE published in 1977. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Bacteremia, Tooth Extraction Status Nos
What is being tested?
0.2% Chlorhexidine, 1% Chlorhexidine and Blood extraction
Could I receive a placebo?
No, everyone receives an active treatment
How many people
208 participants
Where
2 sitesin 2 countries
Study dates
Dec 2010to Jun 2012
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • with need for dental extraction

Who cannot join

  • patients under 18 years of age
  • antibiotic treatment in the previous three months
  • routine use of oral antiseptics
  • any type of congenital or acquired immunodeficiency or other disease that could favour the onset of infection or haemorrhagic complications

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Portugal1 site
  • Department of Stomatology and Maxillofacial Surgery of the Santo Antonio General Hospital

    Porto, Porto District, 4099-001 PORTO

Other trials in Portugal

Spain1 site
  • Department of Stomatology University of Santiago de Compostela

    Santiago de Compostela, Galicia/A Coruña, 15782

Other trials in Spain

About this study

Official title: Bacteraemia Secondary to Tooth Extraction: a Randomized Clinical Trial on Efficacy of Three Different Chlorhexidine Prophylaxis Protocols

The first time the American Heart Association (AHA) suggested that disinfection of the gingival sulcus be performed as a complement to antibiotic prophylaxis in patients considered to be at risk of Infective endocarditis (IE) was in their protocol for the prevention of IE published in 1977. This practice was included by the AHA and adopted by other expert committees such as the British Society for Antimicrobial Chemotherapy (BSAC) in subsequent prophylactic regimens. In 1992, the BSAC specified the presentation and concentration of chlorhexidine (CHX) that should be used before starting the dental procedure: 1% gel at the gingival margin or 0.2% mouthwash for five minutes. In 1997, the AHA recognised the need to use antiseptic mouthwashes (CHX or povidone iodine) prior to dental manipulations, although they recommended against the use of gingival irrigators and against the continuous use of antiseptics in order to avoid the selection of resistant micro-organisms In 2006, the BSAC recommended a single mouthwash with 0.2% CHX gluconate (10 ml for 1 minute) before performing dental procedures associated with bacteraemia in patients at risk of IE. In contrast, in 2007, the AHA recommended against the use of any antiseptic prophylaxis protocol.

In 2008, the National Institute for Health and Clinical Excellence of the United Kingdom recently performed a systematic review of the antimicrobial prophylaxis protocols for IE and reported that: "Oral chlorhexidine used as an oral rinse does not significantly reduce the level of bacteraemia following dental procedures". This conclusion was reached after analysis of numerous studies on the efficacy of prophylaxis with CHX for the prevention of post-dental manipulation bacteraemia. However, those studies presented significant methodological differences not only in the dental procedures performed, but also in the concentration of CHX applied and the method of application of the antiseptic solution (mouthwash and/or irrigation), making comparison of the results of the different series difficult.

Read more

There are few studies that have analysed the efficacy of the mouthwash of 0.2% CHX (the concentration recommended by the BSAC) in the prevention of post-extraction bacteraemia. Only one study analysed the combination of local irrigation and mouthwash with chlorhexidine before dental extraction, but with a really lower concentration of CHX, only 0.02%.

The objective of this study is to investigate the prevalence, duration and aetiology of bacteraemia secondary to a single tooth extraction after prophylaxis with different CHX protocols.

Read the detailed description

The study group will be formed of patients undergoing tooth extraction under local anaesthesia in the Department of Stomatology and Maxillofacial Surgery of the Santo Antonio General Hospital (Oporto, Portugal).The following exclusion criteria will be applied: patients under 18 years of age; antibiotic treatment in the previous three months; routine use of oral antiseptics; and any type of congenital or acquired immunodeficiency or other disease that can favour the onset of infection or haemorrhagic complications. Applying these criteria and after a statistic power test, the sample will be 208 patients. The select patients will be attributed randomly a number of participation and they will be distributed into four groups:

  • Control Group: 52 patients who will use no prophylactic chlorhexidine (CHX) regimen.
  • CHX mouthwash group (CHX-MW group): 52 patients who will perform a mouthwash with 0.2% CHX (10 ml for 1 minute, BSAC recommendations) (Oraldine Perio®, Johnson and Johnson, Barcelona, Spain) before the tooth extraction.
  • CHX mouthwash/subgingival irrigation group (CHX-MW/SUB_IR group): 52 patients who will perform a mouthwash with 0.2% CHX (10 ml for 1 minute) (Oraldine Perio®) and who then will undergo subgingival irrigation with 1% CHX on the tooth to be extracted; the irrigation will be done with the Heraeus Citojet Intraligamental Syringe (CIS) (Kulzer Heraeus S.A., Madrid, Spain) at six points on each tooth (3 points on the vestibular surface and 3 on the palatine surface).
  • CHX mouthwash/supragingival irrigation group (CHX-MW/SUPRA_IR group): 52 patients who will perform a mouthwash with 0.2% CHX (10 ml for 1 minute) (Oraldine Perio®) and who then will undergo supragingival irrigation with 1% CHX on the tooth to be extracted; the irrigation will be done continuously around the tooth to be extracted by a conventional syringe.

The mouthwash and subgingival or supragingival irrigation will be performed before injection of the local anaesthetic.

After recording the sex and age of each patient, a single dentist will perform an intraoral examination 2 days before the intervention, collecting the following information: plaque deposits (simplified Greene and Vermillion oral hygiene index) , calculus deposits (Ramfjord calculus index), presence of gingival bleeding (Löe and Silness gingival index), depth of periodontal pockets (Ramfjord index), degree of tooth mobility (Ramfjord tooth mobility index), number of caries (including root remnants), and presence of submucosal abscesses, fistulae and periapical foci detected clinically and/or radiologically. Each patient will be assigned an overall oral health status using a scale designed by the authors and published previously; the scale incorporates dental and periodontal health criteria.

Local anaesthesia will be administered to all patients using conventional techniques (regional block and/or infiltration). The anaesthetic will be lidocaine plus adrenaline (1:100,000) and not more than 2 cartridges in any patient.

The prevalence of baseline bacteraemia will be determined by collection of a peripheral venous blood sample (10 ml) from each patient before performing any manipulation. The prevalence of bacteraemia secondary to a mouthwash and subgingival or supragingival irrigation will be determined by the collection of a peripheral blood sample (10 ml) 30 seconds after each of these actions. Further samples (10 ml) will be drawn 30 seconds and 15 minutes after completion of the tooth extraction in order to determine the prevalence and duration of post-extraction bacteraemia.

Intravenous access will established using an 18-22 gauge "angiocath" catheter (Becton Dickinson, Sparks, MD, USA) inserted in the antecubital fossa or dorsum of the hand after disinfection of the area with alcohol and povidone iodine. The catheter will be flushed with 3 ml of saline after each extraction and the first 2 ml of blood was discarded. Equal volumes of each sample will be inoculated into two bottles containing aerobic and anaerobic culture media (Bactec Plus, Becton Dickinson), and the bottles will be immediately transferred to the laboratory. The whole process of manipulation and transport of the samples will be performed in accordance with the recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology.

The blood culture bottles into which the blood samples will be injected and processed in the Bactec 9240 (Becton Dickinson). Gram stain will be performed on all positive cultures. The positive aerobic blood cultures will be subcultured on blood agar and chocolate agar in an atmosphere with 5%-10% CO2, and on MacConkey agar under aerobic conditions. The same protocol will be used for the positive anaerobic blood cultures but include subculture on Schaedler agar and incubation under anaerobic conditions. The bacteria isolated will be identified using the battery of biochemical tests provided by the Vitek system (bioMérieux Inc., Hazelwood, Missouri, USA) for gram-positive bacteria, Neisseria spp./Haemophilus spp. and obligate anaerobic bacteria. Applying the Ruoff criteria, Streptococcus viridans will be classified into five groups: mutans, salivarius, bovis, anginosus and mitis.

Being tested
0.2% Chlorhexidine, 1% Chlorhexidine, Blood extraction, Lidocaine plus adrenaline, Tooth extraction
Keywords
prevention and control, chlorhexidine, therapeutic irrigation, mouthwashes, culture
Medical subject headings
Bacteremia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 0.2% ChlorhexidineDrug

    Also called OraldinePerio, Chlorhexidine 0.2%

    mouthwash with 10 ml for 1 minute

  • 1% ChlorhexidineDrug

    Also called Normosept 1g/100ml sloution, Chlorhexidine 1%

    subgingival irrigation

  • 1% ChlorhexidineDrug

    Also called Normosept 1g/100ml solution, Chlorhexidine 1%

    supragingival irrigation

  • Blood extractionProcedure or surgery

    Blood extraction using an intravenous access at baseline, 30 seconds after antiseptic aplication, 30 seconds and 15 minutes after tooth extraction.

  • Lidocaine plus adrenalineDrug

    Also called anaesthesia

    local anaesthesia using lidocaine plus adrenaline (1:100,000) no more than 2 cartridges.

  • Tooth extractionProcedure or surgery

    dental extraction

Study groups in NCT02150031
Study groupRoleWhat they receive
ControlOther* Blood extraction using the intravenous access 18-22 gauge "angiocath" catheter (Becton Dickinson, Sparks, MD, USA) (at baseline, 30 seconds and 15 minutes after tooth extraction). * No prophylactic Chlorhexidine regimen. * Local anesthesia with lidocaine plus adrenaline (1:100,000). * Tooth extraction.
Receives: Procedure: Blood extraction; Drug: Lidocaine plus adrenaline; Procedure: Tooth extraction
CHX-MouthwashActive comparator* Blood extraction using the intravenous access 18-22 gauge "angiocath" catheter (Becton Dickinson, Sparks, MD, USA)(at baseline, 30 seconds and 15 minutes after tooth extraction). * Mouthwash with 0.2% Chlorhexidine (10 ml for 1 minute) (Oraldine Perio®, Johnson and Johnson, Barcelona, Spain). * Local anesthesia with lidocaine plus adrenaline (1:100,000). * Tooth extraction.
Receives: Drug: 0.2% Chlorhexidine; Procedure: Blood extraction; Drug: Lidocaine plus adrenaline; Procedure: Tooth extraction
CHX-MW/SUB_IRActive comparator* Blood extraction using the intravenous access 18-22 gauge "angiocath" catheter (Becton Dickinson, Sparks, MD, USA) (at baseline, 30 seconds and 15 minutes after tooth extraction). * Mouthwash with 0.2% Chlorhexidine (10 ml for 1 minute) (Oraldine Perio®) and subgingival irrigation with 1% Chlorhexidine on the tooth to be extracted; the irrigation will be done with the Heraeus Citojet Intraligamental Syringe (Kulzer Heraeus S.A., Madrid, Spain) at six points on each tooth (3 points on the vestibular surface and 3 on the palatine surface). * Local anesthesia with lidocaine plus adrenaline (1:100,000). * Tooth extraction.
Receives: Drug: 0.2% Chlorhexidine; Drug: 1% Chlorhexidine; Procedure: Blood extraction; Drug: Lidocaine plus adrenaline; Procedure: Tooth extraction
CHX-MW/SUPRA_IRActive comparator* Blood extraction using the intravenous access 18-22 gauge "angiocath" catheter (Becton Dickinson, Sparks, MD, USA)(at baseline, 30 seconds and 15 minutes after tooth extraction). * Mouthwash with 0.2% Chlorhexidine (10 ml for 1 minute) (Oraldine Perio®) and then supragingival irrigation with 1% Chlorhexidine on the tooth to be extracted; the irrigation will be done continuously around the tooth to be extracted by a conventional syringe. * Local anesthesia with lidocaine plus adrenaline (1:100,000). * Tooth extraction.
Receives: Drug: 0.2% Chlorhexidine; Drug: 1% Chlorhexidine; Procedure: Blood extraction; Drug: Lidocaine plus adrenaline; Procedure: Tooth extraction

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in the prevalence of bacteraemia

    Presence of bacteria and how long it lasts in the blood stream.

    Measured: before and 30 seconds after the antiseptic aplication and 30 seconds and 15 minutes after dental extraction.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2014 (estimated)
  2. Study startDec 2010
  3. Primary completionMay 2012
  4. Study completionJun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
208 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02150031
Sponsor's protocol ID
2008/202 CHX bacteraemia
Status last verified
May 2014
First submitted
16 May 2014
Last updated
29 May 2014
Results posted
No
Data monitoring committee
No

Publications

  • Tomas I, Alvarez M, Limeres J, Tomas M, Medina J, Otero JL, Diz P. Effect of a chlorhexidine mouthwash on the risk of postextraction bacteremia. Infect Control Hosp Epidemiol. 2007 May;28(5):577-82. doi: 10.1086/516663. Epub 2007 Apr 5.

    PubMed 17464918
  • Tomas I, Alvarez M, Limeres J, Potel C, Medina J, Diz P. Prevalence, duration and aetiology of bacteraemia following dental extractions. Oral Dis. 2007 Jan;13(1):56-62. doi: 10.1111/j.1601-0825.2006.01247.x.

    PubMed 17241431
  • Benitez-Paez A, Alvarez M, Belda-Ferre P, Rubido S, Mira A, Tomas I. Detection of transient bacteraemia following dental extractions by 16S rDNA pyrosequencing: a pilot study. PLoS One. 2013;8(3):e57782. doi: 10.1371/journal.pone.0057782. Epub 2013 Mar 4.

    PubMed 23469240
  • 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.

    PubMed 20701619
  • Barbosa M, Prada-Lopez I, Alvarez M, Amaral B, de los Angeles CD, Tomas I. Post-tooth extraction bacteraemia: a randomized clinical trial on the efficacy of chlorhexidine prophylaxis. PLoS One. 2015 May 8;10(5):e0124249. doi: 10.1371/journal.pone.0124249. eCollection 2015.

    PubMed 25955349

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 0.2% Chlorhexidine, 1% Chlorhexidine and Blood extraction in people with Bacteremia and Tooth Extraction Status Nos, run by University of Santiago de Compostela at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Portugal, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in the prevalence of bacteraemia (time frame: before and 30 seconds after the antiseptic aplication and 30 seconds and 15 minutes after dental extraction.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02150031, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2014.

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