Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- The number of participants who found the intervention acceptable
研究概览
简要总结
The purpose of this study is to explore whether an anti-cancer medication (5-fluorouracil cream) placed in the vagina after a surgical excision procedure is an acceptable and useful form of treatment for cervical precancer among the woman with HIV infection.
详细描述
There are currently no medical therapies recommended to promote the clearance of human papillomavirus (HPV) infection, regression of cervical dysplasia, or treatment of cervical intraepithelial neoplasia (CIN). Human immunodeficiency virus (HIV)-infected women are at higher risk of HPV infection, with rates as high as 45% - 90%. Despite being preventable, cytologic abnormalities, cervical precancer (high-grade cervical intraepithelial neoplasia [CIN2/3]), and invasive cervical cancer also occur more frequently in HIV infected women.
This study is testing whether topical 5-fluorouracil (5FU) can be used as a patient-controlled adjuvant treatment for cervical precancer (CIN2/3) to be self-administered after surgical excision to reduce the risk of persistent/recurrent CIN2/3 and progression to cervical cancer among HIV-infected women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Confirmed HIV-1 infection
- •On antiretroviral therapy (ART), for at least 90 days prior to enrollment
- •Cervical biopsy demonstrating CIN2/3 within the preceding 120 days.
排除标准
- •pregnancy,
- •breastfeeding,
- •intend to become pregnant within 180 days of enrollment
- •have an active sexually transmitted infection (women may participate once treated)
- •have a surgically absent cervix
- •have a history of anogenital (cervical, vaginal, vulvar, or anal) cancer or a biopsy suspicious for cervical cancer
- •have a medical comorbidity that would interfere with study participation.
研究组 & 干预措施
5 Fluorouracil (5FU) Cream
Participants self-administered 2 grams intravaginal 5FU cream at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).
干预措施: 5 Fluorouracil (5 FU) Cream (Drug)
Placebo Cream
Participants self-administered intravaginal placebo cream (an inert emollient that mimics the 5FU cream) at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).
干预措施: Placebo (Drug)
结局指标
主要结局
The number of participants who found the intervention acceptable
时间窗: week 10 to week 24
The acceptability of the combination of surgical excision followed by adjuvant 5FU for the treatment of CIN2/3 among HIV-infected women will be assessed through a participant questionnaire administered at midline and end of the study.
The number of subjects adhered to and retained in the study
时间窗: Up to 24 weeks
The feasibility of the combination of surgical excision followed by adjuvant 5FU for the treatment of CIN2/3 among HIV-infected women will be evaluated using the number of subjects adhered to and retained in the study.
Number of Participants Retained in the Study Through Week 24
时间窗: Baseline (Week 0) through Week 24
Retention was defined as the number of participants who remained in follow-up and completed the Week 24 study visit. The number and percentage of participants retained at Week 24 were reported for each study arm.
Number of Participants With ≥80% Acceptability Summary Score at Week 10
时间窗: Week 10
Acceptability was defined as a summary score ≥80% on a 7-item questionnaire administered at Week 10. Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28. A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score. The number and percentage of participants meeting this definition were reported for each study arm.
Number of Participants With ≥80% Acceptability Summary Score by Week 24
时间窗: Week 24
Acceptability was defined as a summary score ≥80% on the same 7-item questionnaire administered at Week 24. Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28. A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score. The number and percentage of participants meeting this definition were reported for each study arm.
Number of Participants Experiencing a Treatment-Related Grade ≥2 Adverse Event or Grade 1 Genital Lesion
时间窗: Week 4 (randomization) through Week 24
A safety event was defined as any Grade 2 or higher adverse event (AE), or any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to the study drug. Adverse events were assessed from Week 4 (randomization) through Week 24. The number and percentage of participants experiencing at least one such event were reported for each study arm.
Number of Participants Unable or Unwilling to Apply ≥50% of Study Cream Doses Due to Dose-Limiting Toxicity
时间窗: Week 4 (randomization) through Week 18
A tolerability event was defined as inability or unwillingness to apply ≥4 of 8 planned doses of the study treatment due to a dose-limiting toxicity (DLT). A DLT was defined as (1) any Grade 2 or higher AE, or (2) any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to study drug and resulted in an investigator decision to reduce the number of doses or discontinue study treatment. Tolerability was assessed from randomization through the dosing period (Week 18), with follow-up censored at the last tolerability assessment for participants who exited early without experiencing an event. The number and percentage of participants experiencing a tolerability event were reported for each study arm.
Number of Participants Adherent to ≥75% of Study Cream Doses Based on Ultraviolet Inspection
时间窗: Week 4 (randomization) through Week 24
Adherence was defined as administration of at ≥6 of 8 planned doses of study treatment, as determined by ultraviolet inspection of returned applicators. Applicator collection occurred through Week 24, including for participants who completed dosing earlier, to allow complete ascertainment of dose use. Each applicator was independently assessed by ≥2 reviewers; in cases of disagreement, a third reviewer adjudicated the result. Participants were classified as adherent if ≥6 applicators showed evidence of use. Participants who did not meet this threshold, including those with missing or incomplete applicator data, were classified as non-adherent. The number and percentage of participants meeting this definition were reported for each study arm.
次要结局
- The percentage of participants who demonstrate clearance of high-risk HPV(24 weeks)
- The proportion of participants with CIN2 or CIN 3 that regressed to CIN1(24 weeks)
- Percent of Participants With CIN2/3 at Baseline Who Regressed to CIN1 or Normal Histology at Week 24(Baseline (Week 0) through Week 24)
- Percent of Participants With Baseline High-Risk HPV Who Achieved Genotype-Specific Clearance at Week 24(Baseline (Week 0) through Week 24)