Clinical trial NCT01723956: Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women
Official title: Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Intraepithelial Neoplasia
Keywords: Cervical Dysplasia
Cin 2
Cin 3
HIV positive women
South Africa
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
First posted: 2012-11-08
Enrollment: 166
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.):

1. 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.
2. 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.
3. To compare the safety of cryotherapy versus LLETZ in HIV seropositive women.

SECONDARY AIMS:

1. To describe HIV disease status (CD4, HIV viral load), demographics, and sexual behavior in each treatment arm (LLETZ and cryotherapy) in HIV seropositive women.

3. To determine the cervical disease recurrence rates with cryotherapy and LLETZ.

4. 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.

Eligibility criteria: 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:

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

Primary outcomes:
measure: Compare efficacy of cryotherapy and LEEP
timeFrame: 1 year
Secondary outcomes:
measure: The ability to use Human Papillomavirus as the measure of treatment success
timeFrame: 1 year
measure: To compare the safety of cryotherapy versus LLETZ in HIV seropositive women
timeFrame: 1 month, 6 months and 12 months
measure: Describe factors associated with successful treatment of CIN 2/3
timeFrame: 1 year
measure: To determine the cervical disease recurrence rates with cryotherapy and LLETZ.
timeFrame: 6 months and 12 months
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Helen Joseph Hospital
state: Gauteng
Study officials:
affiliation: University of Witwatersrand, South Africa
name: Cynthia S Firnhaber, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith JS, Sanusi B, Swarts A, Faesen M, Levin S, Goeieman B, Ramotshela S, Rakhombe N, Williamson AL, Michelow P, Omar T, Hudgens MG, Firnhaber C. A randomized clinical trial comparing cervical dysplasia treatment with cryotherapy vs loop electrosurgical excision procedure in HIV-seropositive women from Johannesburg, South Africa. Am J Obstet Gynecol. 2017 Aug;217(2):183.e1-183.e11. doi: 10.1016/j.ajog.2017.03.022. Epub 2017 Mar 31.