VPES: Vanderbilt Pertussis Exposure Study: PEP in Vaccinated Healthcare Workers Following Pertussis Exposure

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00469274
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 1,102
• Location: 1
• Arms: 2
• Duration (Months): 31
• Patients Per Site Per Month: 35.5

Study Details

Study Description

Brief 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 assessment for risk factors associated with healthcare-associated acquisition of pertussis.

Condition or Disease	Intervention/Treatment	Phase
Pertussis	Drug: Antibiotic PEP; Drug: Antibiotic PEP	N/A

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

• Study Type: Interventional
• Actual Enrollment: 1102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomized Open-Label Non-Inferiority Study to Examine the Impact of Pertussis Vaccination of Healthcare Workers on Post-exposure Prophylaxis
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Antibiotic PEP Subjects who did receive PEP following pertussis exposure	Drug: Antibiotic PEP; Azithromycin 1000mg po x 1, then 500mg po Q day for 4 days; TMP-SMX DS one BID for 14 days; Drug: Antibiotic PEP; TMP-SMX DS po BID for 14 days
No Intervention: No PEP Subjects who did not receive PEP following pertussis exposure

Outcome Measures

Primary Outcome Measures

1. Evidence of Pertussis Infection in Each PEP Arm, Defined Using Clinical, Microbiologic, or Serologic Criteria. [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center,	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University
• Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Thomas R. Talbot, MD MPH, Vanderbilt University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tom Talbot, Associate Professor of Medicine, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00469274
• Other Study ID Numbers: VPES
• First Posted: May 4, 2007
• Last Update Posted: Jan 29, 2013
• Last Verified: Dec 1, 2012

• Keywords provided by Tom Talbot, Associate Professor of Medicine, Vanderbilt University: Pertussis; Healthcare worker; Post-exposure prophylaxis; Vaccination; Pertussis in healthcare workers following occupational; exposure to pertussis
• Additional relevant MeSH terms: Whooping Cough; Anti-Bacterial Agents; Antibiotics, Antitubercular

Study Results

Participant Flow

Recruitment Details	Between May 2007 and October 2009, all HCWs working at a 206-bed, tertiary care pediatric acute care hospital were recruited for enrollment. Inclusion criteria were age 18 - 64 years; self-report of direct patient contact; planning to work at least one year from enrollment; and willing to cooperate with surveillance.
Pre-assignment Detail	Subjects were excluded from randomization if they had a previous pertussis exposure within the past 4 weeks; fever, cough, sore throat, or rhinorrhea; received PEP outside of the study; had been vaccinated with Tdap <7 days prior to the exposure; or were recognized as exposed ≥5 days after identification of the infected patient.

Arm/Group Title	No PEP	Antibiotic PEP
Arm/Group Description	Enrolled subjects involved in a pertussis exposure who received no antibiotic post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)	Enrolled subjects involved in a pertussis exposure who received post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)
Period Title: Overall Study
STARTED	44	42
COMPLETED	44	42
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	No PEP	Antibiotic PEP	Total
Arm/Group Description	Enrolled subjects involved in a pertussis exposure who received no antibiotic post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)	Enrolled subjects involved in a pertussis exposure who received post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)	Total of all reporting groups
Overall Participants	44	42	86
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	44 100%	42 100%	86 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (2)	27 (2)	29 (2)
Sex: Female, Male (Count of Participants)
Female	26 59.1%	29 69%	55 64%
Male	18 40.9%	13 31%	31 36%
Region of Enrollment (participants) [Number]
United States	44 100%	42 100%	86 100%

Outcome Measures

1. Primary Outcome

Title	Evidence of Pertussis Infection in Each PEP Arm, Defined Using Clinical, Microbiologic, or Serologic Criteria.
Description	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.
Time Frame	In the 21 days following exposure identification

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	No PEP	Antibiotic PEP
Arm/Group Description	Enrolled subjects involved in a pertussis exposure who received no antibiotic post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)	Enrolled subjects involved in a pertussis exposure who received post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)
Measure Participants	44	42
Number [participants]	6 13.6%	1 2.4%

Adverse Events

Arm/Group Title	No PEP		Antibiotic PEP
Arm/Group Description	Enrolled subjects involved in a pertussis exposure who received no antibiotic post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)		Enrolled subjects involved in a pertussis exposure who received post-exposure prophylaxis as per standard recommendations (i.e. azithromycin 500mg x 1 day followed by 250mg Q day for on days 2-5 or trimethoprm sulfamethoxasole DS BID for 14 days)
All Cause Mortality
	No PEP		Antibiotic PEP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	No PEP		Antibiotic PEP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	No PEP		Antibiotic PEP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/42 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.