Efficacy of Topical 85% TCA in the Treatment of LSIL After Low-grade Abnormality of Screening Test: a Randomized Controlled Trial

NCT ID: NCT06525870

Last Updated: 2024-11-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2025-09-30

Brief Summary

To determine the efficacy and HPV clearance of an application of 85% TCA compared to placebo in the treatment of LSIL. This is a randomized, single-blind, placebo-controlled study in 44 women aged 18-65 years with histologic-proved HPV/CIN1. The study will test whether 85% TCA application will be effective treatment in LSIL. The clinical study hypothesis is that TCA application at cervical lesion and transformation zone will achieve histologic complete remission of LSIL in significantly more patients than placebo therapy. Patients will be randomized to placebo (3% acetic acid) or 85%TCA topical application at cervical lesion and transformation zone. After 3 months, cytology, colposcopy, histology, and HPV testing will be performed. The primary endpoint is treatment efficacy defined as complete histologic remission at 3 months after treatment. The secondary endpoint is HPV clearance 3 months after treatment. The protocol for the project is approved by an Institutional Review Board (IRB). Project is totally supported by a grant from Rajavithi Hospital. There is no external funding.

Detailed Description

The study aims to determine the efficacy and HPV clearance of an application of 85% TCA compared to placebo in the treatment of LSIL. This study will be conducted in women aged 18-65 years with colposcopic-biopsy proved HPV or CIN1, have low grade abnormalities of precolposcopy cervical screening. Low grade abnormalities include ASC-US+HPV positive, LSIL, HPV 16/18, persistent high-risk HPV infection. In patients referred to the colposcopy clinic with ASC-US without HPV testing, they will be eligible if the HPV testing later performed is positive for high risk type. The study will test whether 85% TCA application will be effective treatment in LSIL. The clinical study hypothesis is that TCA application at cervical lesion and transformation zone will achieve histologic complete remission of LSIL in significantly more patients than placebo therapy. A study population is a group of patients who come to gynecology clinic after the histological diagnosis of HPV/CIN I is established. After eligibility is confirmed and demographic data is collected, patients will sign informed consent, a questionnaire will be answered by them and then all patients will have evaluation at pre-intervention check which comprised cytologic test, a type-specific HPV test (if not done previously), a colposcopy colposcopic examination with 3% acetic acid. Detail of colposcopic findings will be recorded. Patients then will be randomized between the two study groups. Group 1 will be intervention arm and receive 85%TCA topical application at cervical lesion and transformation zone. Application of TCA will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators. A thin film of TCA will be applied to cover the lesion and transformation zone. Applying the adjacent endocervial canal and lower part of transformation zone will be cautiously managed by using the wooden stick end of the cotton-tipped applicators soaked with TCA. Protein denaturation and precipitation were confirmed by colposcopic observation of the color change to white. Group 2 will be control arm and receive topical application of 3% acetic acid at cervical lesion and transformation zone in the same manner. At the completion of the treatment, there will be 22 patients in each group. Treatment solutions will be prepared by pharmacy. The treatment is unknown to the patient but the physicians will know because the different degree of cervical tissue whitening. After interventions, the patients will be observed for 5 minutes and will be questioned regarding uncomfortable sensations using a visual analog scale from 0 to 10 (the value 0 is defined as no symptom and 10 worst symptom). Uncomfortable sensations i.e. burning or soreness will be recorded. Patients will be advised to refrain from sexual intercourse, to use sanitary pads rather than tampons, and to shower rather than to take baths for 2 weeks. The patients will be reexamined after 2 weeks following the initial visit. They will be queried about adverse events, since the last visit. Then the patients will be examined by a bivalve vaginal speculum for any evidence of incomplete healing, ulcer and infection. They will be scheduled for second follow-up visit at 3 months after the intervention. A cytologic test, a type-specific HPV test, a colposcopy including multiple guided biopsies will be performed. For the cases with no lesion upon colposcopy, four-quadrant biopsies will be performed from each quadrant of the transformation zone. Assessment of the pathological diagnosis will be done as blindness by pathologists at 3 months after the intervention. The primary endpoint is treatment efficacy defined as complete histologic remission at 3 months after treatment. The secondary endpoint is type-specific HPV clearance at 3 months after treatment. A histologic complete remission (histologic cure) is defined as biopsy-proved normal histology at the time of final colposcopy examination at 3-month follow-up. Because all of patients in this study have low-grade histology, a histologic regression will be defined as biopsy-proved normal histology at the time of final colposcopy examination as well. A histologic progression is defined as CIN2 or worse lesions that are demonstrated on biopsy and histologic persistence is defined as HPV/CIN 1 lesions that are again demonstrated on biopsy at the final colposcopy examination. To determine the sample size, a randomized clinical trial sample size formula where type one (α) error was considered as 5% and the study power as 80% is used. Based on previous studies and considering 46.6% as the difference in complete remission between the two groups. A sample size of 17 patients in each group is needed (α=0.05, power=0.8). Allowing for a dropout rate of 20%, the final sample size is determined to be 22 subjects per group. The total sample size is 44. The analyses will be conducted in all randomized subjects according to the intention-to-treat (ITT) principle. Patients with missing data on remission or regression of LSIL and HPV clearance resulting from refusal to continue participation, and those who failed to appear at scheduled follow-up visits, is regarded as nonresponders. Continuous variables will be summarized by descriptive statistics, including number, mean, median, standard deviation, minimum, and maximum. Categorical variables will be summarized by number and percentage. Independent samples Student's t test to detect mean differences in baseline measures as well as interventions between the two groups. In addition, paired samples t-test is used to detect within-group differences. Pearson Chi-square test is used for comparison of categorical variables. The protocol for the project receives ethics approval from the Institutional Review Board and it is supported by a grant from Rajavithi Hospital. There is no external funding.

Conditions

Cervical Intraepithelial Neoplasia; Trichloroacetic Acid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group 1

Participants will receive 85%TCA topical application at cervical lesion and transformation zone. Application of TCA will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators.

Group Type: EXPERIMENTAL

85%TCA topical application

Intervention Type: DRUG

85%TCA topical application is done at cervical lesion and transformation zone. Application of TCA will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators. A thin film of TCA will be applied to cover the lesion and transformation zone.

Group 2

Participants will receive 3% acetic acid topical application at cervical lesion and transformation zone. Application of 3% acetic acid will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators.

Group Type: PLACEBO_COMPARATOR

3% acetic acid

Intervention Type: DRUG

3% acetic acid topical application is done at cervical lesion and transformation zone. Application will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators. A thin film of acetic acid will be applied to cover the lesion and transformation zone.

Interventions

85%TCA topical application

85%TCA topical application is done at cervical lesion and transformation zone. Application of TCA will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators. A thin film of TCA will be applied to cover the lesion and transformation zone.

Intervention Type: DRUG

3% acetic acid

3% acetic acid topical application is done at cervical lesion and transformation zone. Application will be guided by colposcopy using a small cotton-tipped applicators and wooden end of the applicators. A thin film of acetic acid will be applied to cover the lesion and transformation zone.

Intervention Type: DRUG

Other Intervention Names

Group 1; Group 2

Eligibility Criteria

Inclusion Criteria

• Women, 18-65 years of age, colposcopic biopsy confirmed CIN1 or HPV (LSIL) preceded by low-grade cervical screening test, i.e. ASCUS HPV positive, LSIL, HPV 16/18 positive, persistent high-risk HPV infection.
• Willing to participate in this trial

Exclusion Criteria

• Women diagnosed with previous or concurrent invasive carcinoma of the cervix
• Women with history of pelvic radiotherapy
• Pregnant women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Department of Medical Services Ministry of Public Health of Thailand

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Rajavithi Hospital

Thailand, Bangkok, Thailand

Countries

Thailand

Other Identifiers

136/2567

Identifier Type: -

Identifier Source: org_study_id