- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01824537
Transmission Reduction and Prevention With HPV Vaccination (TRAP-HPV) Study (TRAP-HPV)
Transmission Reduction and Prevention With HPV Vaccination (TRAP-HPV) Study: A Randomized Controlled Trial of the Efficacy of HPV Vaccination in Preventing Transmission of HPV Infection in Heterosexual Couples
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Two prophylactic vaccines (Gardasil by Merck, and Cervarix by GlaxoSmithKline) have been proven in randomized controlled trials (RCT) to be highly effective in preventing infection against the target HPV types (HPV-6, 11, 16 and 18, for Gardasil, and HPV-16/18, for Cervarix) and the cervical precancerous lesions caused by them. These vaccines have shifted the paradigm of prevention and are expected to have a major impact in reducing the burden of cervical cancer and of other HPV-associated malignancies, such as vulvar, vaginal, penile, anal, and oropharyngeal cancers, as well as benign HPV-associated conditions (in the case of Gardasil), such as anogenital warts and respiratory papillomatosis. However, little is known about the extent with which vaccination may reduce transmission between sexual partners; i.e. much remains to be understood on the effects of HPV vaccine in preventing transmission of target HPV types to sexual partners of vaccinated individuals and its impact on herd immunity.
The investigators propose to conduct a placebo-controlled, double-blinded RCT to measure the impact of vaccination in preventing HPV transmission within young (age 18-45) heterosexual couples at McGill and Concordia Universities in Montreal, Canada. Individual partners in 500 couples* will be randomized to a treatment (Gardasil 9) or a control vaccine (Avaxim, a hepatitis A vaccine). This control vaccine provides a similar health benefit incentive as HPV vaccination while preserving the scientific cogency of a "placebo" comparator. Risk factor data will be collected via computerized questionnaires at enrolment (time 0), 2, 4, 6, 9 and 12 months. At all time points, the investigators will measure HPV DNA infection status by PCR in both partners in exfoliated penile, and oral samples from men and vaginal, oral samples from women. Assessing pre-enrolment humoral immune response to HPV infection with a competitive Luminex immunoassay (CLIA) will be done in an enrolment blood sample from all study participants.
The primary outcome will be the reduction of HPV DNA positivity for the target HPV vaccine types (types 6, 11, 16 and 18) in multiple anatomic sites in Avaxim-treated sexual partners of participants who received Gardasil 9. The investigators hypothesize that HPV vaccination is effective in reducing the risk of HPV transmission to their sexual partners. They will use the Kaplan-Meier technique and logrank tests to compare the cumulative probability of HPV infection in sexual partners of vaccinated versus unvaccinated individuals against follow-up time, and Cox proportional hazards regression to estimate the effect of vaccination and other covariates on transmission of HPV to sexual partners. Statistical analyses will follow an intention-to-treat approach but additional regression models will examine the role of several candidate determinants in mediating transmission and the protective effects. Mixed-effects models will also be used to take advantage of the repeated measurements across visits, HPV types, and anatomical sites for the same subject.
In addition to the findings on protection to unvaccinated partners, it is expected that this study will provide valuable insights as to whether protection may exist for a vaccine recipient in preventing infection in an anatomical site in which a target type has not yet established infection. These findings will generate key parameter data to inform the extent of herd immunity in cost-effectiveness models of HPV vaccination. Such models are essential to arrive at rational science-driven policies of HPV vaccination in girls and boys in Canada.
As of March 13, 2020, study visits were temporarily suspended due to the COVID-19 pandemic. With university approval, study visits were resumed as of May 26, 2020. This interruption in study visits lead to slight alterations in the timing of vaccinations, which will be adjusted for in the final analyses as required.
*Due to challenges with participant recruitment, we will complete the study with 500 participants (250 couples), as opposed to the original target of 1000 participants (500 couples). This sample size is achievable based on current recruitment rates and will maintain enough statistical precision for the 2x2 factorial design of the study.
(full protocol available upon request)
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Quebec
-
Montreal, Quebec, Canada, H4A 3T2
- McGill University - Division of Cancer Epidemiology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Couple must have been in a new relationship that started no more than six months prior to study entry
- Both partners plan on remaining in Montreal for at least 1 year
- Plan on having continued sexual contact with partner
- Be willing to comply with study procedures
Exclusion Criteria:
- Volunteers must not have been vaccinated against HPV-Gardasil-9 (both partners)
- Any history of cervical, penile, oral or anal cancers
- Being pregnant or plan on immediately becoming pregnant
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: HPV vaccine, Gardasil 9
HPV vaccine intervention: The intervention vaccine will be Gardasil 9, a 9-valent vaccine by Merck.
This vaccine was chosen because it allows for the observation of 9 HPV outcomes (HPV 6, 11, 16 and 18) (the other available vaccine, Cervarix, protects against HPVs 16 and 18, only).
|
Once recruited, both individuals in a couple will be randomized independently to Gardasil 9 or placebo (Avaxim).
|
Placebo Comparator: Hepatitis A vaccine
The placebo comparator will be Avaxim, by Sanofi Pasteur.
This control vaccine was chosen because hepatitis A immunization provides a similar health prevention incentive as HPV vaccination to study participants while preserving the scientific cogency of a "placebo" comparator.
Gardasil 9 requires administration of 3 doses, while Avaxim only requires 2 doses.
For this reason, a placebo injection (saline solution) will be added in between the Avaxim vaccination regimen.
Consequently, both treatment and control vaccines will have similar regimens, i.e., study entry, 2 months, and 6 months.
|
Provided by Sanofi Pasteur.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The primary outcome will be the reduction of HPV DNA positivity for the target HPV vaccine types (i.e., HPVs 6, 11, 16, and 18) in multiple anatomic sites in the placebo-treated sexual partners of persons who received Gardasil.
Time Frame: At months 2, 4, 6, 9 and 12.
|
Reduction in HPV type concordance (for the four target types) will be the main outcome evaluable as per the above group contrasts.
These comparisons will be done with due attention to the enrolment virological status of the individuals.
For instance, it is expected that a Avaxim-treated woman who is positive for HPV 6 in the oral specimen but negative for this type in the vaginal specimen may derive benefit if her partner receives Gardasil, even if he is HPV-6 positive in the penile sample.
The assumption is that protection via vaccination is pan-mucosal, via transudation of neutralizing antibodies; this protection may mediate transmission.
|
At months 2, 4, 6, 9 and 12.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Mariam El-Zein, PhD, McGill University
Publications and helpful links
General Publications
- MacCosham A, El-Zein M, Burchell AN, Tellier PP, Coutlee F, Franco EL; TRAP-HPV study group. Protection to Self and to One's Sexual Partner After Human Papillomavirus Vaccination: Preliminary Analysis From the Transmission Reduction And Prevention with HPV Vaccination Study. Sex Transm Dis. 2022 Jun 1;49(6):414-422. doi: 10.1097/OLQ.0000000000001620. Epub 2022 Mar 2.
- MacCosham A, El-Zein M, Burchell AN, Tellier PP, Coutlee F, Franco EL. Transmission reduction and prevention with HPV vaccination (TRAP-HPV) study protocol: a randomised controlled trial of the efficacy of HPV vaccination in preventing transmission of HPV infection in heterosexual couples. BMJ Open. 2020 Aug 11;10(8):e039383. doi: 10.1136/bmjopen-2020-039383. Erratum In: BMJ Open. 2020 Aug 24;10(8):e039383corr1.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CIHR-MOP-125949
- IIS #38265 (Other Grant/Funding Number: Merck)
- MOP-125949 (Other Grant/Funding Number: Canadian Institutes of Health Research)
- FDN-143347 (Other Grant/Funding Number: Canadian Institutes of Health Research)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Human Papillomavirus Infection
-
The AlfredMerck Sharp & Dohme LLCCompletedHuman Papillomavirus Infection | Human PapillomavirusAustralia
-
Centre Hospitalier Universitaire de BesanconCompletedHuman Papillomavirus InfectionFrance
-
University Hospital, GenevaCompletedHuman Papillomavirus InfectionSwitzerland
-
University of ConnecticutCompletedHuman Papillomavirus Infection
-
Indiana UniversityMerck Sharp & Dohme LLCUnknownHuman Papillomavirus InfectionUnited States
-
Gen-Probe, IncorporatedCompletedHuman Papillomavirus InfectionUnited States
-
GlaxoSmithKlineCompletedHuman Papillomavirus Infection
-
GlaxoSmithKlineCompletedHuman Papillomavirus InfectionEgypt
-
University Hospital, GenevaUnknown
-
Gen-Probe, IncorporatedCompletedHuman Papillomavirus InfectionUnited States
Clinical Trials on HPV vaccine, Gardasil 9
-
Miquel Angel Pavon RibasCatalan Institute of Health; Hospital del MarRecruitingCervical Intraepithelial Neoplasia Grade I/ II/ III (CIN I/II/III) | Human Papillomavirus (HPV) Infections | High-risk HPV | HPV-16/ 18Spain
-
Shanghai Zerun Biotechnology Co.,LtdWalvax Biotechnology Co., Ltd.Active, not recruitingCervical Cancer | Papillomavirus Infections | CIN | Genital Wart | VINChina
-
Shanghai Bovax Biotechnology Co., Ltd.Chongqing Bovax Biopharmaceutical Co., Ltd.CompletedCervical Cancer | Vulvar Cancer | Vaginal Cancer | CIN1 | CIN2 | CIN3 | VaIN1 | VaIN2 | VaIN3 | Genital Wart | VIN 1 | VIN 2 | VIN 3 | AISChina
-
University Health Network, TorontoMerck Sharp & Dohme LLCNot yet recruitingAnal Cancer | Human Papilloma Virus | Anal Intraepithelial NeoplasiaCanada
-
Laval UniversityCompleted
-
AIDS Malignancy ConsortiumNational Cancer Institute (NCI); University of California, Los Angeles; Merck... and other collaboratorsActive, not recruitingHIV Infection | AIDS-Related Human Papillomavirus Infection | High Grade Cervical Squamous Intraepithelial NeoplasiaUganda, Kenya, Zimbabwe, South Africa, Malawi
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Evandro Chagas National Institute of Infectious... and other collaboratorsActive, not recruitingHIV InfectionPeru, Brazil, Haiti
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Allogeneic Hematopoietic Stem Cell Transplant RecipientUnited States
-
University of Alabama at BirminghamMerck Investigator Studies ProgramNot yet recruiting