Efficacy and Safety of TCA vs. ECA for the Treatment of AIN in HIV-positive Patients (TECAIN)

November 7, 2022 updated by: Stefan Esser M.D., University Hospital, Essen

Efficacy and Safety of Topical Trichloroacetic Acid vs. Electrocautery for the Treatment of Anal Intraepithelial Neoplasia in HIV-positive Patients (TECAIN) - a Randomized Controlled Trial

Comparative evaluation of efficacy and safety of high-resolution anoscopy (HRA)-guided topical treatment (trichloroacetic acid, TCA) vs. surgical treatment (electrocautery, ECA) in HIV-positive patients for human papillomavirus (HPV)- induced AIN, an anal cancer precursor. The primary hypothesis is that cost-saving and simple TCA treatment is non-inferior to the current best option therapy with ECA. TCA treatment would also be possible in the normal setting of a doctor´s office without extensive specialization and without complex technical equipment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Anal human papillomavirus (HPV)-infection and HPV-induced AIN, an anal cancer precursor, are very frequent in HIV-positive patients (HIV+), especially in men who have sex with men (MSM), but also in women. Consequently, HIV+ have a strongly increased risk for anal cancer. Screening for and treatment of AIN are recommended in HIV+, although only two RCT on AIN treatment have been published. We plan a multicenter, unblinded, non-inferiority RCT that evaluates the efficacy and safety of 2 high-resolution anoscopy (HRA)-guided treatment options for AIN: topical application of trichloroacetic acid (TCA) and surgical treatment with electrocautery (ECA).

ECA was the best option for intra-anal AIN in a recent randomized controlled trial (RCT). TCA, an inexpensive and established therapy for genital warts, has been evaluated for AIN only in a retrospective pilot study that showed clearance rates comparable to those found for ECA, with possibly less adverse events (AE). Our primary hypothesis is that cost-saving and simple TCA is non-inferior to ECA. 2800 HIV+ will be screened by HRA in 9 proctological centers and 560 HIV+ with histologically confirmed intra-anal AIN will be randomized (1:1) to receive up to 4 treatments with TCA or ECA within 12 weeks. The primary efficacy endpoint is clinical (HRA) and histological resolution of AIN 4 weeks after the last treatment. Secondary endpoints comprise recurrence of AIN 24 weeks after end of therapy, the number of interventions, AE, and the influence of HPV parameters such as anal HPV-types, viral load and HPV-oncogene-mRNA.

Study Type

Interventional

Enrollment (Actual)

560

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Nordrheinwestfalen
      • Essen, Nordrheinwestfalen, Germany, 45147
        • Universitätsklinikum Essen, Klinik für Dermatologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV positive patients
  • Legally eligible patients and age ≥ 18 years
  • Sufficient knowledge of the German language, spoken and written
  • Patient is willing and able to appear regularly to the treatment- and follow-up appointments
  • Clinically visible AIN-lesion, which was confirmed by histopathology (findings not older than 2 weeks after the date of collection and removal date no longer than 16 weeks prior to baseline)
  • Written informed consent

Exclusion Criteria:

  • Currently diagnosed anal cancer or anal cancer in anamnesis (within the last 5 years)
  • Acute life-threatening disease
  • Participation in a proctologic study within the last 30 days
  • Participation in this study at an earlier date
  • Simultaneous participation in another clinical trial, which excludes the participation in this study
  • Simultaneous topical and systemic treatments wtih medications that affect the study outcome, such as immunomodulatory substances: Interferone, imiquimod or systemic glucocorticosteroids
  • lactation
  • Pregnancy: In patients of childbearing age, a pregnancy has to be ruled out by pregnancy test or other suitable methods.
  • Women of childbearing potential without adequate contraceptive protection.
  • Contraindication for using trichloroacetic acid or electrocautery
  • Patients in whom general anesthesia in the treatment of AIN is necessary already at study start
  • Other serious intra-anal and proctologic disorders, which make additional proctologic or systemic treatments necessary, which influence the study result, such as an active Crohn's disease, which must be treated locally and systemically with immunosuppressives or an active proctitis.
  • Patients who have been vaccinated before baseline against HPV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Topical 85% trichloroacetic acid (TCA)
AIN lesions are treated with trichloric acid
Other: Topical 85% trichloroacetic acid (TCA)
In the experimental intervention arm, all visible lesions are treated with 85% TCA by dipping the wooden stick end of a cotton swab into a cup containing TCA. The stick end is saturated with TCA and is inserted through the anoscope and directed to the lesion under HRA guidance. TCA is applied to the lesion repeatedly until the lesion changes to a dense white colour. Each TCA application session is followed by another appointment four weeks later, where the clinician re-evaluates the lesions of the patient and determines whether a next TCA application is necessary up to a maximum of four times
Other Names:
  • Topical treatment with trichloroacetic acid (TCA)
Active Comparator: Surgical electrocautery (ECA)
AIN lesions are treated with electrocautery
Procedure: Surgical electrocautery (ECA)
In the control arm, HRA-guided ECA, is performed every 4 weeks up to a maximum of four times. All visible lesions are ablated at every visit. Bleeding from small vessels can be stopped by ECA. Patients undergo local anaesthesia if necessary
Other Names:
  • Device: Electrocauter

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapeutic success (success rate) defined as clinically (HRA) and histologically confirmed resolution (normal histology) or regression (from AIN2/3 to AIN1) of AIN
Time Frame: Four weeks after the last treatment within TECAIN
The primary endpoint is therapeutic success (success rate) defined as clinically (HRA) and histologically confirmed resolution (normal histology) or regression (from AIN 2/3 to AIN1) of AIN four weeks after the last treatment within TECAIN. Patients not showing up at this mandatory follow-up appointment will be counted as treatment failure. Histologically confirmed resolution/regression 4 (to 8) weeks after therapy has been the primary endpoint in the two published RCTs and in several pilot studies. Clearance of AIN after treatment is the most relevant endpoint for patients, since AIN can rapidly progress to AC in HIV+ patients.
Four weeks after the last treatment within TECAIN

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence of AIN at the previously treated sites
Time Frame: 24 weeks after the end of TECAIN treatment
24 weeks after the end of TECAIN treatment
Number of interventions needed during the 12 weeks TECAIN treatment period.
Time Frame: 4 weeks after the end of TECAIN treatment
Additional treatments are possible after baseline, but they are not mandatory, if the lesions are cleared. So 4 weeks after each treatment the investigator checks, if the lesions are cleared and decides if he does another treatment or if the patient can progress to the follow up
4 weeks after the end of TECAIN treatment
Pain of the proctologic AIN treatments
Time Frame: Up to 16 weeks after study start
Additional treatments are possible after baseline, but they are not mandatory, if the lesions are cleared. So 4 weeks after each treatment the investigator checks, if the lesions are cleared and decides if he does another treatment or if the patient can progress to the follow up
Up to 16 weeks after study start
Anal HPV types, HPV multiplicity, HPV DNA load and HPV oncogene mRNA
Time Frame: Baseline, 4 and 24 weeks after the end of TECAIN treatment
Baseline, 4 and 24 weeks after the end of TECAIN treatment
Recurrence of AIN or new lesions
Time Frame: 6 months after completion of TECAIN treatment in previously treated areas
6 months after completion of TECAIN treatment in previously treated areas
Duration of treatment phase
Time Frame: 24 weeks after the end of TECAIN treatment
24 weeks after the end of TECAIN treatment
Adverse events
Time Frame: During the whole study up to 36 weeks
During the whole study up to 36 weeks
Treatment costs
Time Frame: 24 weeks after the end of TECAIN treatment
24 weeks after the end of TECAIN treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Essen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2015

Primary Completion (Actual)

March 31, 2020

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

November 19, 2015

First Submitted That Met QC Criteria

November 23, 2015

First Posted (Estimate)

November 26, 2015

Study Record Updates

Last Update Posted (Actual)

November 8, 2022

Last Update Submitted That Met QC Criteria

November 7, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01KG1425

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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