Adjuvant 5-Fluorouracil Following Thermal Ablation to Improve HPV Treatment Outcomes in Women With HIV in Kenya : The ASCEND Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- High-risk human papillomavirus (hrHPV) Clearance among WWH randomized to adjuvant self-administered 5FU cream versus placebo cream following Thermal ablation (TA)
研究概览
简要总结
This randomized, placebo-controlled trial will evaluate self-administered 5-fluorouracil (5FU) to improve human papillomavirus (HPV) clearance after thermal ablation (TA) in Women With Human Immunodeficiency Virus (HIV) (WWH) in Kenya. The trial will also assess the safety, adherence, and acceptability of 5FU. Starting four weeks after TA, participants will self-administer 5FU cream or matched placebo intravaginally once every other week for 12 applications, with clinic visits at weeks 2, 8, 16, 24, and 48 for evaluation. All participants will be followed up to 48 weeks.
It is hypothesized that, compared to placebo, 5FU will increase HPV clearance at 24 weeks and that the proposed dosing schedule will be safe, well-tolerated, and acceptable in this population. Together with data from other studies, this trial will provide evidence on the use of self-administered intravaginal 5FU to improve HPV treatment outcomes in WWH in low- and middle-income countries, where the burden of cervical cancer is highest.
详细描述
WWH face up to six times higher risk of cervical cancer, a leading cause of death in this population. Cervical cancer is caused by persistent HPV infection, which can lead to cervical intraepithelial neoplasia grade 2/3 (CIN2/3), also called cervical precancer. If untreated, CIN2/3 can progress to cervical cancer. Thermal ablation (TA) is the most commonly used treatment for HPV/precancer in low- and middle-income countries, including Kenya. However, among WWH, TA has suboptimal efficacy, with only 44-66% clearing HPV or CIN2/3 at 6-12 months, compared to 83-95% in women without HIV. This highlights the need for adjuvant therapies to improve outcomes.
Studies in high-income countries suggest that off-label, self-administered intravaginal 5FU cream can improve HPV and CIN2/3 treatment outcomes in both HIV-negative and HIV-positive women. This trial will evaluate its potential as an adjuvant therapy following TA in WWH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 25 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 25 years or older
- •Known HIV-positive status
- •On antiretroviral therapy (ART) for at least 60 days prior to enrollment
- •Positive HPV screening test screening result
- •Able to provide informed consent in English, Swahili, or Dholuo
- •Agree to use dual contraception during dosing phase if of childbearing potential
- •Planning to remain in study locale for duration of study (48 weeks)
排除标准
- •Current pregnancy or breastfeeding
- •History of anogenital cancer (cervical, vulvar, or anal)
- •Current use of immunosuppressive medications
- •History of total hysterectomy
- •Known allergy to 5FU
- •Medical comorbidity that would interfere with study participation
- •Unwilling or unable to use contraception during study participation
研究组 & 干预措施
5% 5-fluorouracil
Participants will receive 12 doses of intravaginal 5FU cream.
干预措施: 5% 5-fluorouracil Topical Cream (Drug)
Placebo cream
Participants will receive 12 doses of intravaginal placebo cream.
干预措施: Placebo Cream (Drug)
结局指标
主要结局
High-risk human papillomavirus (hrHPV) Clearance among WWH randomized to adjuvant self-administered 5FU cream versus placebo cream following Thermal ablation (TA)
时间窗: Up to 24 weeks
Vaginal samples will be collected at baseline and approximately every four weeks. Clearance of hrHPV genotypes will be assessed using Polymerase Chain Reaction (PCR)-based human papillomavirus (HPV) Deoxyribonucleic Acid (DNA) testing on these follow-up samples.
次要结局
- Adverse Event per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0(24 weeks)
- Adverse Event per National Institute of Health (NIH) Division of Acquired Immunodeficiency Syndrome (AIDS) Adverse Event Grading Criteria (DAIDS)(Up to 24 weeks)
- Number of successful self-administration of the intravaginal cream by participants(Up to 24 weeks)