Cervical Precancer, Human Immunodeficiency Virus, Human Papillomavirus
Conditions
Keywords
intravaginal, self-administer, artesunate, intravaginal artesunate, vaginal pessaries
Brief summary
The objective of this randomized, placebo-controlled trial is to evaluate whether intravaginal artesunate pessaries (vaginal inserts) can be used as adjuvant therapy following thermal ablation to improve Human papillomavirus (HPV) treatment outcomes in Women Living with Human Immunodeficiency Virus (WLWH). The study will evaluate whether women who use artesunate will have higher HPV clearance at 6 months, compared to those who used a placebo. The study will also assess the safety, adherence, and acceptability of this treatment. 120 participants will be enrolled in the study. Participants will self-administer the study drug nightly for 5 days, take a week off, and repeat twice (use study drug on weeks 1, 3,5) and will return to the clinic on weeks 2, 4, 6, 12, and week 24 for follow-up.
Detailed description
WLWH face up to six times increased risk of cervical cancer, as a result, cervical cancer is a leading cause of death in this population. Cervical cancer is caused by persistent infection with the human papillomavirus (HPV), resulting in precancerous changes that if not adequately treated, progress to cancer. Thermal ablation is a commonly used treatment for cervical precancer in Kenya and other low- and middle-income countries (LMICs). Current treatments for HPV or cervical precancer, including thermal ablation, are associated with high rates of treatment failure in WLWH. In a recent study from Zambia, only 44% of WLWH had cleared HPV at six months following thermal ablation treatment. Other studies have demonstrated up to 30% recurrence rate of high-grade cervical precancer at 12 to 24 months after treatment. Persistent infection with HPV following precancer treatment is a key risk factor for treatment disease recurrence.
Interventions
Subjects will self-administer 200 mg of Artesunate vaginal insert daily for 5 days, on weeks 1, 3, 5.
DRUGPlacebo vaginal inserts
Subjects will self-administer a placebo vaginal insert daily for 5 days, on weeks 1, 3, 5.
Sponsors
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Kenya Medical Research Institute
Maseno University School of Medicine, Kenya
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 25 years or older * Known HIV seropositive status * On antiretroviral therapy for \> 90 days prior to enrollment * Weight ≥50 Kg at study entry\* * Positive HPV screening test and within 4-8 weeks of thermal ablation * Ability to provide informed consent * Planning to stay within the study locale during the duration of the study (24 weeks) * Agreement to use contraception (barriers or hormonal) if of childbearing age through week 6 of the study
Exclusion criteria
* Current pregnancy or breastfeeding status * Current or past history of invasive cervical cancer * History of total hysterectomy * Currently receiving systemic chemotherapy or radiation therapy for another cancer * Current use of systemic immunosuppressants or steroids (\>10 mg of prednisone or equivalent) * Current use of efavirenz antiretroviral therapy, phenytoin, carbamazepine, and rifampin * Have medical comorbidity that, in the opinion of the investigator, would interfere with study participation * Prior chemotherapy within 30 days prior to day 1 of study treatment * Male at birth
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clearance of type-specific HPV genotype(s) | 24 weeks | The number and proportion of women in each study arm who demonstrate clearance of the specific HPV genotype, or genotypes (if multiple) between baseline and six months will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adherence | Week 6 | Adherence will be evaluated based on the number and proportion of women confirmed self-administration of at least 80% (12 of 15) vaginal inserts. |
| Acceptability measured by acceptability questionnaire | Week 6 | Acceptability will be evaluated based on a close-ended structured acceptability questionnaire. The responses will be on a Likert score, between 1-5, and higher scores represent better accepted. |
Countries
Kenya
Contacts
PRINCIPAL_INVESTIGATORChemtai Mungo, MD, MPH
UNC Lineberger Comprehensive Cancer Center
Outcome results
None listed