VICAR2: Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women

Sponsor

University of Witwatersrand, South Africa (Other)

Overall Status

Completed

CT.gov ID

NCT01723956

Collaborator

(none)

166

Enrollment

Location

Arms

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and Human Papillomavirus.

Hypothesis: LEEP will be more effective than cryotherapy in removing CIN 2/3 lesions in HIV positive women in South Africa

Condition or Disease	Intervention/Treatment	Phase
Cervical Intraepithelial Neoplasia	Procedure: Cryotherapy Procedure: LEEP	N/A

Detailed Description

Cervical cancer is the most common cancer in HIV positive women. This is due to immunosuppression and lack of organized and effective screening and treatment programs in Africa. Other screening and treatment modalities need to be evaluated in resource limited countries as there is not capacity in most of these countries to implement a cytology/histology based program. The treatment modality of cryotherapy is easy to train and perform and can be done by a nurse. LEEP requires significant training usually doctors and skills in administering local anaesthetic. This study compares the two modalities of cryotherapy vs LEEP in a randomized controlled study in HIV positive women in South Africa.

A. PRIMARY AIMS (S.A.):

To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.
To determine the utility of subsequent HPV DNA testing as a marker of effective treatment following the treatment of CIN 2/3 among HIV-seropositive women.
To compare the safety of cryotherapy versus LLETZ in HIV seropositive women.

SECONDARY AIMS:

To describe HIV disease status (CD4, HIV viral load), demographics, and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.
To determine the cervical disease recurrence rates with cryotherapy and LLETZ.
To evaluate the relationship between HIV status, demographics, HPV, and sexual behavior with the clearance of cervical disease at the ectocervical and endocervical margins in HIV seropositive women.

Study Design

Study Type:

Interventional

Actual Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm B LEEP treatment of CIN 2/3 cervical lesion in HIV positive women (standard of Care)	Procedure: LEEP The cervix is anaesthetized with lidocaine and then a electric loop is applied to the cervical lesion which is cut with one pass. The LEEP machine used is the automatic Finesse Machine. Other Names: Loop Electric Excision Procedure
Experimental: Arm A Cryotherapy treatment of CIN 2/3 cervical lesions	Procedure: Cryotherapy This is involves freezing the lesions with a cryo gun using Nitrous Oxide for 3 minutes-- wait 5 minutes and then refreezing for 3 more minutes. This procedure uses the Wallach cryogun Other Names: This is a study using Freezing with a cryogun

Arm

Intervention/Treatment

Active Comparator: Arm B

LEEP treatment of CIN 2/3 cervical lesion in HIV positive women (standard of Care)

Procedure: LEEP

The cervix is anaesthetized with lidocaine and then a electric loop is applied to the cervical lesion which is cut with one pass. The LEEP machine used is the automatic Finesse Machine.

Other Names:

Loop Electric Excision Procedure

Experimental: Arm A

Cryotherapy treatment of CIN 2/3 cervical lesions

Procedure: Cryotherapy

This is involves freezing the lesions with a cryo gun using Nitrous Oxide for 3 minutes-- wait 5 minutes and then refreezing for 3 more minutes. This procedure uses the Wallach cryogun

Other Names:

This is a study using Freezing with a cryogun

Outcome Measures

Primary Outcome Measures

Compare efficacy of cryotherapy and LEEP [1 year]
To compare the efficacy of cryotherapy and large loop excision of the transformation zone (LLETZ) procedures for the treatment of high-grade cervical intra-epithelial neoplasia (CIN2/3) among HIV-seropositive women by follow-up VIA, cytology and HPV.

Secondary Outcome Measures

The ability to use Human Papillomavirus as the measure of treatment success [1 year]
To determine the utility of subsequent HPV DNA testing as a marker of effective treatment following the treatment of CIN 2/3 among HIV-seropositive women.
To compare the safety of cryotherapy versus LLETZ in HIV seropositive women [1 month, 6 months and 12 months]
To compare the safety of cryotherapy versus LLETZ in HIV seropositive women by evaluating adverse events as measured by the Division of AIDS toxicity table 2004 (revised August 2010)
Describe factors associated with successful treatment of CIN 2/3 [1 year]
To describe HIV disease status (CD4, HIV viral load), demographics, tissue margins and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.
To determine the cervical disease recurrence rates with cryotherapy and LLETZ. [6 months and 12 months]
To determine the cervical disease recurrence rates with cryotherapy and LLETZ at 6 months and 12 months by colposcopy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women 18-65 years of age
Not menstruating (if menstruating, the patient can be screened at another date)
Able to sign consent
Able to follow the study protocol
HIV positive (by two different criteria; either 2 different rapid HPV tests of different manufacturers, a HIV viral load ≥5,000,ELISA, Western blot documented in VICAR 1)
Participant with histology-proven CIN 2 or 3 disease

Exclusion Criteria:

Pregnant
Clinically active sexually transmitted disease determined by clinical history and/or physical exam (may participate after adequate treatment by syndromic treatment management)
Known and previous treatment for high grade squamouse intraepithelial lesion by any method (cryotherapy, LLETZ or cone biopsy)
Previous hysterectomy with removal of the cervix
Significant medical illness/mental illness that the investigator feels would prevent the participant from complying with the protocol or place the participant at medical risk
Cervical dysplastic lesions that are not appropriate for cryotherapy, defined as the following:

Lesion is greater than ≥75% cervix
Lesion entering into the cervical canal and the complete lesion cannot be visualized
Presence of abnormal vasculature
Lesion bigger that the cryotherapy probe