Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT01824537 |
| Other study ID # |
CIHR-MOP-125949 |
| Secondary ID |
IIS #38265MOP-12 |
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
September 2013 |
| Est. completion date |
December 2022 |
Study information
| Verified date |
October 2022 |
| Source |
McGill University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Human papillomavirus (HPV) is a member of the Papillomaviridae family of DNA viruses that is
capable of infecting humans. HPV infection can cause cancers of the cervix, vulva, vagina,
and anus in women or cancers of the anus and penis in men. Two prophylactic vaccines have
been proven to be highly effective in preventing the acquisition of HPV infection and the
genital precancerous lesions caused by it. However, we do not know yet if a previously
infected individual, once vaccinated, would be less infective to her or his sexual partner.
We plan to conduct a study, called Transmission Reduction And Prevention with HPV vaccination
(TRAP-HPV) study to answer this question. It will include 500 sexually active couples* (total
of 1000 individuals) in university student health clinics in Montreal (age 18-45 years). It
will be a randomized placebo-controlled, double-blinded intervention trial. Study
participants will be followed up to 12 months. Behavioural and biological data will be
collected at the time of study enrolment, then at months 2, 4, 6, 9 and 12 post-enrolment.
The results of this trial will be invaluable in informing policies regarding vaccination of
women and men.
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)
