A Randomized Trial To Compare An HPV Test-And-Treat Strategy To A Cytology-Based Strategy For Prevention Of CIN 2+ In HIV-Infected Women
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 467
- 试验地点
- 13
- 主要终点
- Cumulative Rate of Cervical Intraepithelial Neoplasia (CIN2+) (CIN2, CIN3 or Invasive Cancer) by Week 130
研究概览
简要总结
Women sometimes develop cancer in an area called the cervix, which is the opening to the uterus, or womb. Women who have HIV are more likely to get this kind of cancer than women who do not have HIV. Nearly all of these cancers are caused by another virus, called human papilloma virus (or HPV). Other times, the cause of this cancer is not known.
The investigators are looking for a better way to prevent cervical cancer. This study is comparing two different methods to prevent cancer of the cervix in women who have HIV. This study will also see if these methods are safe and tolerable in women who have HIV.
详细描述
The study had two components:
- a randomized open-label comparison between immediate cryotherapy (test-and-treat strategy; Arm A) and cytology-based strategy (Arm B) in participants detected with high-risk HPV (hr-HPV), and
- a brief cohort follow-up for participants for whom cryotherapy was inappropriate (Arm C).
The study's primary objective was to evaluate the effectiveness of immediate cryotherapy (Arm A) compared to the cytology-based strategy (Arm B).
The total target sample size was up to 450 (280 for Arms A and B, approximately 170 for Arm C). Randomization to Arms A and B was stratified by use of antiretroviral therapy (ART) at screening (taking any ART or not taking any ART) with institutional balancing.
All study participants were screened with the Abbott RealTime hr-HPV test (aHPV) to detect hr-HPV infection.
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
- None
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
- •HIV-1 infection.
- •Certain laboratory values obtained within 45 days prior to study entry (more information can be found in the protocol).
- •For candidates suitable for cervical cryotherapy, hr-HPV detected by aHPV within 45 days prior to study entry.
- •For women without hr-HPV detected by the aHPV assay, presence of lesions on visual inspection or HSIL cervical cytology. These participants are not eligible for randomization to Arms A or B and were followed in Arm C.
- •Suitable candidate for cervical cryotherapy (as defined in the protocol): No visible cervical lesions, OR (a) any visible lesions were located entirely on the ectocervix and were no more than 2 to 3 mm. into the endocervical canal, AND (b) visible lesions covered less than 75% of the cervix, AND (c) all visible lesions were deemed appropriate for cryotherapy by the treating local health care provider.
- •NOTE: Participants with cervical lesions inappropriate for cryotherapy are not eligible for randomization to Arms A or B and were followed in Arm C.
- •For participants of reproductive potential, negative pregnancy test within 48 hours prior to study entry.
- •Must agree not to participate in a conception process (e.g. active attempt to get pregnant or in vitro fertilization), or use at least one reliable contraceptive if participating in sexual activity, from time of study entry until 12 weeks after study entry.
- •If recently gave birth, must be at least 12 weeks postpartum.
- •Ability and willingness of participant or legal guardian/representative to provide written informed consent.
排除标准
- •Current or prior history of cervical, vaginal, or vulvar cancer.
- •Prior cervical cryotherapy, LEEP, cervical conization, or total or partial hysterectomy.
- •Cervical, vaginal, or vulvar lesions that are suspicious on clinical exam for cancer.
- •Visual evidence of bacterial STIs (sexually transmitted infections) or suspicion of pelvic inflammatory disease.
- •Prior vaccination with an HPV vaccine.
- •Hemophilia.
- •Currently on anticoagulation therapy other than acetylsalicylic acid.
- •Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to study entry.
- •Active drug or alcohol use or dependence or any other condition that, in the opinion of the site investigator, would interfere with the participant's ability to adhere to study requirements.
研究组 & 干预措施
Arm A: Immediate cryotherapy (HPV test-and-treat)
Participants in Arm A (HPV test-and-treat) had cervical cryotherapy at entry. Post entry, participants in Arm A were seen at regular intervals for the collection of cervical specimens, cytology, and as needed, cervical colposcopy, directed biopsies, and LEEP.
干预措施: Cervical Cryotherapy (Procedure)
Arm A: Immediate cryotherapy (HPV test-and-treat)
Participants in Arm A (HPV test-and-treat) had cervical cryotherapy at entry. Post entry, participants in Arm A were seen at regular intervals for the collection of cervical specimens, cytology, and as needed, cervical colposcopy, directed biopsies, and LEEP.
干预措施: Loop Electrosurgical Excision Procedure (LEEP) (Procedure)
Arm B: cytology-based strategy
Participants in Arm B followed a cytology-based management plan involving three steps- cytology, colposcopy with directed biopsies, and LEEP (as needed).
干预措施: Loop Electrosurgical Excision Procedure (LEEP) (Procedure)
Arm C : Ineligible for randomization to Arm A or B
Participants were eligible for Arm C under the conditions noted in the inclusion criteria. Participants in Arm C had colposcopy and directed biopsies at entry. If CIN2+ was found by biopsy, then LEEP was performed and a follow-up visit 26 weeks after these procedures was scheduled for the collection of cervical specimens, cytology, and as needed, cervical colposcopy, directed biopsies, and LEEP. After the week 26 visit, Arm C participants went off study.
干预措施: Loop Electrosurgical Excision Procedure (LEEP) (Procedure)
结局指标
主要结局
Cumulative Rate of Cervical Intraepithelial Neoplasia (CIN2+) (CIN2, CIN3 or Invasive Cancer) by Week 130
时间窗: Weeks 26, 52, 78, 104 and 130 post randomization
The Kaplan-Meier estimate of the cumulative rate of CIN2+ (CIN2, CIN3 or invasive cancer) by week 130. Time to CIN2+ was computed as the number of weeks between randomization and the week 26 to week 130 biopsy week when CIN2+ was first detected. For those who did not develop CIN2+, event time was censored at the latest among the following: time of last biopsy or last colposcopy or last pap smear. CIN2+ diagnosis by biopsy was determined by local review at a DAIDS-assessed laboratory.
次要结局
- Cumulative Rate of CIN3+ (CIN3 or Invasive Cancer) by Week 130.(Weeks 26, 52, 78, 104 and 130 post randomization)
- Number of Participants With Abnormal Cytology Results at Study Visits.(Weeks 26, 52, 78, 104 and 130 post randomization)
- Time to CIN2+ Diagnosis by Biopsy, as Determined by Local Review at a DAIDS-assessed Laboratory.(Weeks 26, 52, 78, 104 and 130 post randomization)
- Number of Participants Who Discontinued Study Early.(0 to 130 weeks post randomization)
- Number of Participants With High Risk (hr)-HPV by the Abbott Real Time High-risk HPV Assay (aHPV) at Study Visits.(Weeks 26, 52, 78, 104 and 130 post randomization)
- Number of Participants With High Risk (hr)-HPV by the Xpert HPV Assay at Study Visits.(Weeks 26, 52, 78, 104 and 130 post randomization)
- Number of Participants With High Risk (hr)-HPV by the Roche Linear Array HPV Genotyping Test at Study Visits.(Weeks 26, 52, 78, 104 and 130 post randomization)
- Percentage of Participants With Targeted Adverse Events (AEs) Reported Post Cryotherapy in Arm A.(4 weeks post cryotherapy)
- Percentage of Participants With Targeted AEs Reported Post LEEP.(4 weeks post LEEP)