NCT01315353

Brief Summary

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
467

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2012

Longer than P75 for not_applicable

Geographic Reach
7 countries

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 15, 2011

Completed
1.1 years until next milestone

Study Start

First participant enrolled

April 4, 2012

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 11, 2018

Completed
Last Updated

May 11, 2018

Status Verified

May 1, 2018

Enrollment Period

4.8 years

First QC Date

March 14, 2011

Results QC Date

February 1, 2018

Last Update Submit

May 10, 2018

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

  • Cumulative Rate of Cervical Intraepithelial Neoplasia (CIN2+) (CIN2, CIN3 or Invasive Cancer) by Week 130

    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.

    Weeks 26, 52, 78, 104 and 130 post randomization

Secondary Outcomes (9)

  • 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

  • Cumulative Rate of CIN3+ (CIN3 or Invasive Cancer) by Week 130.

    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 Abnormal Cytology Results at Study Visits.

    Weeks 26, 52, 78, 104 and 130 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

  • +4 more secondary outcomes

Study Arms (3)

Arm A: Immediate cryotherapy (HPV test-and-treat)

EXPERIMENTAL

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.

Procedure: Cervical CryotherapyProcedure: Loop Electrosurgical Excision Procedure (LEEP)

Arm B: cytology-based strategy

EXPERIMENTAL

Participants in Arm B followed a cytology-based management plan involving three steps- cytology, colposcopy with directed biopsies, and LEEP (as needed).

Procedure: Loop Electrosurgical Excision Procedure (LEEP)

Arm C : Ineligible for randomization to Arm A or B

EXPERIMENTAL

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.

Procedure: Loop Electrosurgical Excision Procedure (LEEP)

Interventions

Cervical CryotherapyPROCEDURE

Participants had cervical cryotherapy within 7 days after study entry. The cryotherapy consists of two 3-minute freezes separated by 5 minutes of thawing.

Arm A: Immediate cryotherapy (HPV test-and-treat)
Loop Electrosurgical Excision Procedure (LEEP)PROCEDURE

Loop Electrosurgical Excision Procedure (LEEP): Participants found to have CIN2+ by biopsy had LEEP, an electro-surgical procedure used to treat high-grade cervical dysplasia.

Arm A: Immediate cryotherapy (HPV test-and-treat)Arm B: cytology-based strategyArm C : Ineligible for randomization to Arm A or B

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Gaborone Prevention/Treatment Trials CRS (12701)

Gaborone, Botswana

Location

Molepolole Prevention/Treatment Trials CRS (12702)

Molepolole, Botswana

Location

Les Centres GHESKIO CRS (30022)

Port-au-Prince, HT-6110, Haiti

Location

BJ Medical College CRS (31441)

Pune, Maharashtra, 411001, India

Location

National AIDS Research Institute Pune CRS (11601)

Pune, Maharashtra, 411026, India

Location

College of Med. JHU CRS (30301)

Blantyre, Malawi

Location

University of North Carolina Lilongwe CRS (12001)

Lilongwe, Malawi

Location

Investigaciones Medicas en Salud (INMENSA) (11302)

San Isidro, Lima region, Peru

Location

Asociacion Civil Impacta Salud y Educacion - Miraf CRS (11301)

Lima, 18 PE, Peru

Location

Durban Adult HIV CRS (11201)

Durban, 4013 SF, South Africa

Location

Soweto ACTG CRS (12301)

Johannesburg, South Africa

Location

Univ. of Witwatersrand CRS (11101)

Johannesburg, South Africa

Location

UZ-Parirenyatwa CRS (30313)

Harare, Zimbabwe

Location

Related Links

Results Point of Contact

Title
ACTG Clinicaltrials.gov Coordinator
Organization
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
ACTGCT.Gov@s-3.com
(301) 628-3313

Study Officials

  • Timothy J Wilkin, MD, MPH

    Cornell Clinical Research Site

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2011

First Posted

March 15, 2011

Study Start

April 4, 2012

Primary Completion

February 1, 2017

Study Completion

February 1, 2017

Last Updated

May 11, 2018

Results First Posted

May 11, 2018

Record last verified: 2018-05

Locations

HA(1)IN(2)BO(2)ZI(1)MA(2)PE(2)ZA(3)