PertussisVPESNCT00469274
Vanderbilt Pertussis Exposure Study: PEP in Vaccinated Healthcare Workers Following Pertussis Exposure
A study testing Antibiotic PEP in people with Pertussis, run by Vanderbilt University at 1 site in United States.
Trial summary
The purpose of this study is to compare the effectiveness of two strategies of post-exposure prophylaxis (PEP) in healthcare workers (HCWs) who have been vaccinated with acellular pertussis vaccine and have been exposed to pertussis Secondary Objectives include a comparison of the costs of each PEP strategy and an… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Pertussis
- What is being tested?
- Antibiotic PEP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,102 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Dec 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults age 18 - 64 years
- HCW (defined as any healthcare provider with direct patient care duties) who works at VCH (may be primary or secondary place of employment)
- Willing to sign informed consent and authorization for release of information to the Occupational Health Clinic (OHC) at Vanderbilt University
- Planning to work at VCH for at least one year after enrollment or until anticipated study termination, whichever comes first
- Willing to cooperate with disease and microbiologic surveillance
Who cannot join
- Prior receipt of an acellular pertussis vaccine within 5 years prior to enrollment, unless received since Tdap licensure on June 13, 2005
- History of tetanus booster in the 2 years prior to enrollment (excluding Tdap)
- History of allergic or adverse reaction to diphtheria, tetanus, or pertussis vaccines
- Current pregnancy or attempting to become pregnant in the month after enrollment
- Any contraindication to receipt of pertussis vaccine as listed in the ADACEL package insert
- Febrile illness with temperature greater than 38 degrees C in the previous 72 hours (defer enrollment)
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- Persons receiving erythromycin, azithromycin, or related antibiotic for prolonged use
- Persons allergic to both macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin) and sulfa antibiotics
- Any condition which, in the opinion of the investigators, may interfere with the evaluation of the study objectives
Trial locations and contacts
1 site in 1 country.
United States1 site
Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center,
Nashville, Tennessee, 37232
About this study
Official title: A Randomized Open-Label Non-Inferiority Study to Examine the Impact of Pertussis Vaccination of Healthcare Workers on Post-exposure Prophylaxis
The purpose of this study is to compare the effectiveness of two strategies of post-exposure prophylaxis (PEP) in healthcare workers (HCWs) who have been vaccinated with acellular pertussis vaccine and have been exposed to pertussis Secondary Objectives include a comparison of the costs of each PEP strategy and an assessment for risk factors associated with healthcare-associated acquisition of pertussis.
Read the detailed description
Pertussis, caused by the bacterium Bordetella pertussis, is an acute respiratory tract infection transmitted to susceptible persons through aerosolized respiratory droplets and direct contact with respiratory secretions. Classic pertussis disease is characterized by three phases of illness: the catarrhal phase where persons note cough and coryza; the paroxysmal phase where persons develop a spasmodic cough with post-tussive vomiting and an inspiratory whoop; and the convalescent phase, during which symptoms slowly resolve. The risk of transmission of the organism is compounded by the nondescript nature of symptoms early in the course of illness, particularly in adults. Classically recognized as a disease of infants and children ("whooping cough"), the incidence of pertussis infection in adolescents and adults has increased in recent years. Persons >15 years of age now make up more than twenty percent of reported cases. This increase is likely due to several factors, including waning protection from childhood vaccination and natural infection, an increased appreciation for disease in adolescents and adults, and the improved ability of clinicians to diagnose pertussis recognition through the use of serologic methods.
Healthcare workers (HCWs) are at increased risk for acquiring pertussis infection due to regular contact with infected patients and waning protection from childhood vaccination or from natural pertussis infection. Healthcare-associated outbreaks of pertussis have also been increasingly recognized and have been reported from a diverse range of healthcare facilities. Such outbreaks are often due to under-recognition of pertussis with subsequent failure to isolate suspected cases, waning immunity from childhood vaccination or disease, and the increasing incidence of pertussis infection in adults and adolescents. Infected HCWs can then serve as vectors of infection to other susceptible contacts including patients, other employees, and even their own children.
Vaccination is an effective tool for the prevention of pertussis. In 2005, two tetanus toxoid, reduced diphtheria toxoid, and reduced antigen quantity acellular pertussis vaccines (Tdap) were licensed for use in adolescents and adults. In view of the increasingly recognized problem of healthcare-associated and transmitted pertussis infection, the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) targeted HCWs as a priority group for pertussis vaccination in 2006, primarily to reduce the risk of spread of pertussis within health care institutions.
Until the licensure of Tdap, the only method to reduce transmission of pertussis after healthcare-associated exposure to persons with pertussis was post-exposure prophylaxis (PEP) with antibiotics and employee furlough. Close contacts exposed to a pertussis-infected patient or staff member are routinely treated with macrolide therapy (erythromycin or azithromycin), and exposed HCWs who develop a cough-illness are restricted from work for 5 days while on antibiotic therapy. PEP is believed to prevent symptomatic infection in the exposed person if administered within 21 days of cough onset. Traditionally, decisions regarding PEP for exposed HCWs involve detailed assessments of the degree of patient contact, the risk for development of severe or complicated pertussis, and regular evaluation and follow-up for the occurrence of symptoms. These are often time-consuming efforts that are usually the responsibility of infection control or occupational health personnel. With the licensure of Tdap and with the recommended vaccination of HCWs, it is now hoped that vaccination will eliminate the need to provide antibiotic PEP, particularly in recently-vaccinated HCWs. However, this has not been confirmed with a randomized clinical trial, and, therefore, no definitive formal recommendation can be made regarding modifications of PEP in vaccinated HCWs. Two potential strategies exist for the management of vaccinated HCWs following an exposure to a person with pertussis: a) provision of universal antibiotic therapy or b) careful daily observation of vaccinated HCWs for the development of symptoms without antibiotic prescription. A comparison of these two strategies will be the focus of this study.
- Conditions
- Pertussis
- Being tested
- Antibiotic PEP
- Keywords
- Pertussis, Healthcare worker, Post-exposure prophylaxis, Vaccination, Pertussis in healthcare workers following occupational, exposure to pertussis
- Medical subject headings
- Whooping Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antibiotic PEPDrug
Azithromycin 1000mg po x 1, then 500mg po Q day for 4 days; TMP-SMX DS one BID for 14 days
Antibiotic PEPDrug
TMP-SMX DS po BID for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Antibiotic PEP | Active comparator | Subjects who did receive PEP following pertussis exposure Receives: Drug: Antibiotic PEP |
| No PEP | No intervention | Subjects who did not receive PEP following pertussis exposure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of Pertussis Infection in Each PEP Arm, Defined Using Clinical, Microbiologic, or Serologic Criteria.
Defined as a positive nasopharyngeal culture or PCR for B. pertussis at any time point, a two-fold rise in the anti-PT IgG titer between acute and convalescent sera, or a single acute or convalescent anti-PT IgG titer of ≥94 EU. Post hoc, a modified definition was devised because of concern that the serologic criteria used in the primary definition might actually represent acquisition of pertussis infection prior to the intervention. The modified definition of pertussis excluded an acute anti-PT IgG titer of ≥94 EU and an acute nasopharyngeal swab that was positive for B. pertussis by PCR.
Measured: In the 21 days following exposure identification
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2007 (estimated)
- Study startMay 2007
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PertussisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Tom Talbot, Vanderbilt University
- Investigators
- Thomas R. Talbot, MD MPH, Principal investigator, Vanderbilt University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00469274
- Sponsor's protocol ID
- VPES
- Acronym
- VPES
- Status last verified
- Dec 2012
- First submitted
- 3 May 2007
- Last updated
- 29 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Goins WP, Edwards KM, Vnencak-Jones CL, Rock MT, Swift M, Thayer V, Schaffner W, Talbot TR. A comparison of 2 strategies to prevent infection following pertussis exposure in vaccinated healthcare personnel. Clin Infect Dis. 2012 Apr;54(7):938-45. doi: 10.1093/cid/cir973. Epub 2012 Jan 11.
PubMed 22238169
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Open-Label Non-Inferiority Study to Examine the Impact of Pertussis Vaccination of Healthcare Workers on Post-exposure Prophylaxis
- ClinicalTrials.gov ID
- NCT00469274
- Acronym / sponsor ID
- VPES / VPES
- Conditions
- Pertussis
- Keywords
- Pertussis, Healthcare worker, Post-exposure prophylaxis, Vaccination, Pertussis in healthcare workers following occupational, exposure to pertussis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,102 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- May 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 4 May 2007 (estimated)
- Results
- Posted 29 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the effectiveness of two strategies of post-exposure prophylaxis (PEP) in healthcare workers (HCWs) who have been vaccinated with acellular pertussis vaccine and have been exposed to pertussis Secondary Objectives include a comparison of the costs of each PEP strategy and an assessment for risk factors associated with healthcare-associated acquisition of pertussis.
Detailed description
Pertussis, caused by the bacterium Bordetella pertussis, is an acute respiratory tract infection transmitted to susceptible persons through aerosolized respiratory droplets and direct contact with respiratory secretions. Classic pertussis disease is characterized by three phases of illness: the catarrhal phase where persons note cough and coryza; the paroxysmal phase where persons develop a spasmodic cough with post-tussive vomiting and an inspiratory whoop; and the convalescent phase, during which symptoms slowly resolve. The risk of transmission of the organism is compounded by the nondescript nature of symptoms early in the course of illness, particularly in adults. Classically recognized as a disease of infants and children ("whooping cough"), the incidence of pertussis infection in adolescents and adults has increased in recent years. Persons >15 years of age now make up more than twenty percent of reported cases. This increase is likely due to several factors, including waning protection from childhood vaccination and natural infection, an increased appreciation for disease in adolescents and adults, and the improved ability of clinicians to diagnose pertussis recognition through the use of serologic methods.
Healthcare workers (HCWs) are at increased risk for acquiring pertussis infection due to regular contact with infected patients and waning protection from childhood vaccination or from natural pertussis infection. Healthcare-associated outbreaks of pertussis have also been increasingly recognized and have been reported from a diverse range of healthcare facilities. Such outbreaks are often due to under-recognition of pertussis with subsequent failure to isolate suspected cases, waning immunity from childhood vaccination or disease, and the increasing incidence of pertussis infection in adults and adolescents. Infected HCWs can then serve as vectors of infection to other susceptible contacts including patients, other employees, and even their own children.
Vaccination is an effective tool for the prevention of pertussis. In 2005, two tetanus toxoid, reduced diphtheria toxoid, and reduced antigen quantity acellular pertussis vaccines (Tdap) were licensed for use in adolescents and adults. In view of the increasingly recognized problem of healthcare-associated and transmitted pertussis infection, the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) targeted HCWs as a priority group for pertussis vaccination in 2006, primarily to reduce the risk of spread of pertussis within health care institutions.
Until the licensure of Tdap, the only method to reduce transmission of pertussis after healthcare-associated exposure to persons with pertussis was post-exposure prophylaxis (PEP) with antibiotics and employee furlough. Close contacts exposed to a pertussis-infected patient or staff member are routinely treated with macrolide therapy (erythromycin or azithromycin), and exposed HCWs who develop a cough-illness are restricted from work for 5 days while on antibiotic therapy. PEP is believed to prevent symptomatic infection in the exposed person if administered within 21 days of cough onset. Traditionally, decisions regarding PEP for exposed HCWs involve detailed assessments of the degree of patient contact, the risk for development of severe or complicated pertussis, and regular evaluation and follow-up for the occurrence of symptoms. These are often time-consuming efforts that are usually the responsibility of infection control or occupational health personnel. With the licensure of Tdap and with the recommended vaccination of HCWs, it is now hoped that vaccination will eliminate the need to provide antibiotic PEP, particularly in recently-vaccinated HCWs. However, this has not been confirmed with a randomized clinical trial, and, therefore, no definitive formal recommendation can be made regarding modifications of PEP in vaccinated HCWs. Two potential strategies exist for the management of vaccinated HCWs following an exposure to a person with pertussis: a) provision of universal antibiotic therapy or b) careful daily observation of vaccinated HCWs for the development of symptoms without antibiotic prescription. A comparison of these two strategies will be the focus of this study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Antibiotic PEP | Active comparator | Drug: Antibiotic PEPSubjects who did receive PEP following pertussis exposure |
| No PEP | No intervention | –Subjects who did not receive PEP following pertussis exposure |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Adults age 18 - 64 years
- HCW (defined as any healthcare provider with direct patient care duties) who works at VCH (may be primary or secondary place of employment)
- Willing to sign informed consent and authorization for release of information to the Occupational Health Clinic (OHC) at Vanderbilt University
- Planning to work at VCH for at least one year after enrollment or until anticipated study termination, whichever comes first
- Willing to cooperate with disease and microbiologic surveillance
Key exclusion criteria (9 listed)
- Prior receipt of an acellular pertussis vaccine within 5 years prior to enrollment, unless received since Tdap licensure on June 13, 2005
- History of tetanus booster in the 2 years prior to enrollment (excluding Tdap)
- History of allergic or adverse reaction to diphtheria, tetanus, or pertussis vaccines
- Current pregnancy or attempting to become pregnant in the month after enrollment
- Any contraindication to receipt of pertussis vaccine as listed in the ADACEL package insert
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Antibiotic PEPAzithromycin 1000mg po x 1, then 500mg po Q day for 4 days; TMP-SMX DS one BID for 14 days | Drug | Antibiotic PEP |
| Antibiotic PEPTMP-SMX DS po BID for 14 days | Drug | Antibiotic PEP |
Primary outcome
Evidence of Pertussis Infection in Each PEP Arm, Defined Using Clinical, Microbiologic, or Serologic Criteria.
Time frame: In the 21 days following exposure identification
Defined as a positive nasopharyngeal culture or PCR for B. pertussis at any time point, a two-fold rise in the anti-PT IgG titer between acute and convalescent sera, or a single acute or convalescent anti-PT IgG titer of ≥94 EU. Post hoc, a modified definition was devised because of concern that the serologic criteria used in the primary definition might actually represent acquisition of pertussis infection prior to the intervention. The modified definition of pertussis excluded an acute anti-PT IgG titer of ≥94 EU and an acute nasopharyngeal swab that was positive for B. pertussis by PCR.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22238169Goins WP, Edwards KM, Vnencak-Jones CL, Rock MT, Swift M, Thayer V, Schaffner W, Talbot TR. A comparison of 2 strategies to prevent infection following pertussis exposure in vaccinated healthcare personnel. Clin Infect Dis. 2012 Apr;54(7):938-45. doi: 10.1093/cid/cir973. Epub 2012 Jan 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas R. Talbot, MD MPH principal investigator
Vanderbilt University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Antibiotic PEP in people with Pertussis, run by Vanderbilt University at 1 site in United States.
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 5 inclusion and 9 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 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Evidence of Pertussis Infection in Each PEP Arm, Defined Using Clinical, Microbiologic, or Serologic Criteria. (time frame: In the 21 days following exposure identification). 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 NCT00469274, which also lists 1 linked publication.
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 Jan 2013.