Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05431699 |
| Other study ID # |
22-108 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 13, 2023 |
| Est. completion date |
December 2027 |
Study information
| Verified date |
December 2023 |
| Source |
The Cleveland Clinic |
| Contact |
Miriam Cremer, M.D. |
| Phone |
216-312-0618 |
| Email |
cremerm[@]ccf.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to validate a new low-cost, self-collected HPV screening test
(ScreenFire) and compare it to the standard provider collected careHPV, for the detection of
high grade cervical cancer.
Description:
Study Design:
Interventional study
Study Procedures:
Enrollment: Given our previous experience24 it will be feasible to enroll 60 women per week
to comfortably meet our recruitment goal of 12,000 women in 50 months. MOH community health
promoters will provide community outreach and schedule appointments for eligible women.
Eligible women who consent will complete a brief intake questionnaire in a private room and
be instructed on how to properly perform a self-collection of ScreenFire. After
self-collecting the HPV ScreenFire test, women will have a provider-collected careHPV test
during a standard speculum exam. All COVID-19 precautions will be carefully followed. To be
enrolled, all participants will need to complete both HPV screening methods.
Self-collection of ScreenFireHPV: Participants will be invited to complete HPV primary
screening by self-collection on the same day that they attend the clinic. The nurse will
provide illustrated instructions about this process (see Figure 2), answer any questions,
then show the participant to a private room. Self-samples are collected by gently inserting a
sterile dry swab into the vagina until the woman feels resistance, rotating the brush five
full 360° turns, withdrawing the swab, placing it into the tube, breaking off the top portion
of the swab, and closing and returning the tube to the study nurse. Self-collected dry
samples can be stored without preservative at room temperature and are stable for at least 32
weeks.31 Self-collected specimens will be analyzed per manufacturer's instructions with the
ScreenFire platform at a local lab. Each participant's HPV test will be recorded as negative
or positive, and if positive the specific HPV category(ies) will be recorded and uploaded
into the REDCap database. The HPV categories are the following: Group 1 (HPV type 16); Group
2 (HPV types 18 and 45); Group 3 (HPV types 33,31,52,58,35); and Group 4 (HPV types
39,51,59,56,68).
Study Population:
The investigators will enroll 12,000 women from clinics in El Salvador. The ScreenFire PCR
machine has been used in El Salvador for COVID testing, and laboratory personnel are already
trained on how to correctly run the machine.
Key personnel:
At study start-up, Drs. Cremer and Wang will launch the trial in El Salvador in person, if
possible, or virtually if COVID restrictions remain in place. Once the clinical trial begins,
the team will have bi-monthly phone calls to discuss study progress and any potential issues.
Study personnel will visit each of the 152 participating clinics. All interviews, consents,
and exams will be performed by study staff, with administrative assistance from MOH community
health center workers. Samples will be sent to a local laboratory.
Data Collection & Management:
Pathologist readings: Cervical biopsies will be transported study personnel to senior
pathologists in San Salvador.36-38 Local pathology results will be used for referral to
treatment per standard-of-care guidelines.39 Gynecologic pathologists from the United States
will evaluate the slides with CIN2+ diagnoses and a 5% random sample of CIN1/normal pathology
slides on a regular basis to ensure quality and for expert confirmation of study endpoints.
The evaluation may be done in person or remotely using a slide scanner. It is important to
have the pathologists differentiate CIN2 from CIN3 diagnoses, given recent epidemiological
evidence that CIN3 is more likely to progress to invasive cervical cancer (ICC).40-42 For
disagreement in diagnosis, a third expert pathologist will adjudicate the discrepancy.
Pathologists will be blinded to HPV status and to each other's diagnoses.
Analysis Plan:
The primary analysis will evaluate the sensitivity of self-collected ScreenFire versus
standard provider-collected careHPV for the detection of high-grade cervical precancer
(CIN2+) in HPV+ women. Women who are HPV negative are unlikely to have high-risk precancer,
therefore only a subset (5%) of the HPV negative women will be screened with colposcopy and
undergo biopsy.3,43 Histology results from those 5% randomly selected HPV negative
participants who attend colposcopy (N=475) will allow correction for potential verification
bias. Maximum likelihood estimates (MLEs)44 will be used to provide statistically valid
estimates of sensitivity and corresponding 95% confidence intervals (CIs). The secondary
analysis will involve estimation of the specificity, positive predictive value (PPV), and
negative predictive value (NPV) of primary high-risk HPV testing in ScreenFire
self-collection vs. careHPV provider-collection for CIN2+ detection using similar MLE
estimates as described above. For CIN3+ endpoints, the investigators will assess test
performance (sensitivity, specificity, NPV, PPV) for self-collected ScreenFire and
provider-collected careHPV as descriptive analyses.
Non-participation documentation:
Demographic characteristics and reasons for ineligibility and/or declining trial
participation will be recorded for patients who are asked to participate but do not enroll in
the study. Those who decline participation will be invited to fill out the demographic form
so data can be gathered on non-participation. Data will be used to evaluate possible
selection bias to inform interpretation of study findings.
Statistical power and sample size:
Based on screening 12,000 women, and a 12% estimate of HPV positivity to either ScreenFire
HPV in self-collected samples or careHPV in provider-collected samples, the investigators
expect 1,440 HPV+ women. Assuming a 90% retention from HPV screening to colposcopy, 1,296 are
expected to have colposcopy-directed biopsy results. Based on our previous work with HPV+
women in El Salvador,45 the investigators conservatively estimate 10% CIN2+ prevalence among
HPV+ women and 130 CIN2+ cases. There is 80% power to detect a 5% difference in sensitivity
of ScreenFire self-collection for CIN2+ detection versus careHPV provider collection (88% vs
93%) at a significance level 0.05. That is, there will be sufficient power to determine that
the sensitivity of ScreenFire self-collection for CIN2+ is higher than careHPV
provider-collection. There is an 80% power to detect a 4% difference in specificity of
ScreenFire self-collection for CIN2+ detection versus careHPV provider-collection (84% vs
88%) at a significance level of 0.05.
