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Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia

Primary Purpose

Cervical Dysplasia

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
LLETZ
LEEP
Sponsored by
Ruhr University of Bochum
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Dysplasia focused on measuring cervical dysplasia, conization, surgery, cervical cancer, LLETZ, LEEP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed High Grade Squamous Intraepithelial Lesion (HSIL)
  • Colposcopically visible lesion
  • No therapy of the disease so far

Exclusion Criteria:

  • Pregnancy of the patient at/after inclusion in the study; pregnancy after conization and before the control after 6 months is possible and does not lead to exclusion from the study.
  • Taking immunosuppressive drugs (incl. glucocorticoids)
  • Known HIV positivity
  • Malignant disease requiring treatment
  • Unsatisfactory colposcopy

Sites / Locations

  • Dept. OBGYN Ruhr University BochumRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

LLETZ group

LEEP group

Arm Description

LLETZ (large loop excision of the transformation zone) is one of several possible surgical interventions for treating cervical dysplasia.

LEEP (loop electrosurgical excision procedure) is one of several possible surgical interventions for treating cervical dysplasia.

Outcomes

Primary Outcome Measures

Surgical specimen margin status
Oncological safety as defined by the rate of specimens with involved margins, i.e. cervical dysplasia present at the edge of the surgical specimen.

Secondary Outcome Measures

Intraoperative and postoperative complication rate
Rate of complications such as excessive bleeding, re-operation, unplanned readmission, infection
Cone size
Size of the resected tissue
Patient's pain
Pain experienced by the patients (11-item Visual Analogue Scale); minimum 0 (no pain), maximum 10 (unbearable pain)
HPV clearance
HPV high-risk positivity by PCR
Cone volume
Volume of the resected tissue

Full Information

First Posted
February 22, 2021
Last Updated
March 28, 2023
Sponsor
Ruhr University of Bochum
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1. Study Identification

Unique Protocol Identification Number
NCT04772937
Brief Title
Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia
Official Title
Comparison of Two Surgical Approaches in the Treatment of Cervical Dysplasia: Complete Removal of the Transformation Zone (LLETZ) Versus Isolated Resection of the Colposcopically Visible Lesion (LEEP)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 7, 2021 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruhr University of Bochum

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Cervical dysplasia is the precursor of cervical cancer. LEEP and LLETZ are standard surgical procedures to treat cervical dysplasia. There is no direct head-to-head comparison between LEEP and LLETZ in the literature regarding oncologic safety, for which complete resection of the dysplastic lesion (so-called 'in-sano resection') is the most appropriate postoperative surrogate parameter. Further clinical studies are therefore useful to optimize surgical therapy for cervical dysplasia. The primary objective of the present study is to compare LLETZ (resection of the dysplastic lesion including the transformation zone) with targeted resection of the colposcopically conspicuous lesion only (LEEP) and to compare it with regard to oncological safety (defined as non-in-sano rate).
Detailed Description
Cervical cancer is one of the most common cancers in women and one of the leading causes of death in women worldwide. Pre-cancerous lesions (dysplasias) are detected by the preventive smear test at the gynecologist and can thus contribute to a 100% chance of cure if they are clarified by a colposcopic examination as part of the dysplasia consultation and dysplastic lesions are then surgically removed if necessary (conization). In practice, there are four different methods by which conization can be performed: Knife Conization, Laser Conization, Large Loop Excision of the Transformation Zone (LLETZ) and Loop Electrical Excision Procedure (LEEP). The first three methods have in common that they aim to remove the entire transformation zone. The rationale for this is that both the precancerous lesions and the cervical carcinoma itself originate in the transformation zone of the cervix. This thesis would support the idea of resecting the lesion while taking the remaining healthy transformation zone along as a precaution. However, it is clear that with the removal of the entire transformation zone, healthy tissue is removed in addition to the lesion itself. Any increase in radicality may increase the complication rate of the procedure, especially with regard to the most feared long-term complication of preterm birth, because the more cervical tissue is removed, the higher the risk of subsequent preterm birth. This connection speaks in favor of the use of LEEP, in which only the visible dysplastic tissue in healthy tissue is removed in the sense of a radical resection, without at the same time also removing the entire transformation zone, especially in women who still wish to have children. In summary, the aim of conization is on the one hand to achieve a high level of oncological safety (low recurrence rate, high R0 resection rate) by resecting sufficient dysplastic tissue, and on the other hand to avoid excessive tissue resection, because this would increase the risk of premature birth in a subsequent pregnancy. There is no direct head-to-head comparison between LEEP and LLETZ in the literature regarding oncologic safety, for which complete resection of the dysplastic lesion (so-called 'in-sano resection') is the most appropriate postoperative surrogate parameter. In a Pubmed literature search (search date: February 10, 2021, search terms: conization, LEEP, LLETZ, resection margin, randomized), no prospective randomized study on this topic was found. Further clinical studies are therefore useful to optimize surgical therapy for cervical dysplasia The primary objective of the present study is to compare LLETZ (resection of the dysplastic lesion including the transformation zone) with targeted resection of the colposcopically conspicuous lesion only (LEEP) and to compare it with regard to oncological safety (defined as non-in-sano rate). For this purpose, patients with histologically confirmed CIN II/III will be randomly assigned to one of the two surgical methods. In order to exclude an unwanted influence by unconsciously different behavior of the patients, the patient will only learn about the surgical method performed on her after the control examination 6 months postoperatively (unilateral blinding). The surgeon is not blinded for obvious technical reasons. However, in case of complications, access to the surgical report and the chosen method is possible at any time. Immediately postoperatively, the specimen is examined histologically and evaluated with regard to the depth of the conus and the degree of dysplasia as well as the resection margins (R0= free resection margin; R1= dysplasia extends to the resection margin) by a pathology specialist. After an interval of 6-8 months, the first follow-up examination (the so-called "test of cure") with PAP smear and HPV test is performed in accordance with the guidelines. The two groups are compared with regard to normalization of the Pap smear, HPV status and colposcopic findings (including histology in the case of colposcopic abnormalities). For patients with negative HPV test, unremarkable cytology, histology and colposcopy, the study is terminated. These patients are considered cured and discharged to regular screening with their established gynecologist. In case of abnormalities, the further procedure is determined according to the usual clinical criteria in conformity with the guidelines: clinical control after 3 and/or 6 months or re-conization. Secondary target criteria of the study are, in addition to the intra- and postoperative complication rate, the pain perception of the patients and the intraoperative blood loss, also the rate of negative high risk HPV tests after 6-8 months, since a negative HPV test is generally regarded as evidence of successful treatment. Thus, the negative predictive value for a negative HPV test after conization ranges from 92% to 100%. Successful therapy usually results in elimination of the HP virus. Accordingly, a negative HPV test excludes CIN persistence or recurrence with a high probability. In contrast, a persistently positive HPV test may be taken as an indication of persistence of dysplasia or as an indicator of recurrent dysplasia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Dysplasia
Keywords
cervical dysplasia, conization, surgery, cervical cancer, LLETZ, LEEP

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomization, 1:1 allocation, group 1: LLETZ, group 2: LEEP
Masking
Participant
Masking Description
Patient is anesthetized during surgery and will not recognize type of surgery.
Allocation
Randomized
Enrollment
206 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LLETZ group
Arm Type
Other
Arm Description
LLETZ (large loop excision of the transformation zone) is one of several possible surgical interventions for treating cervical dysplasia.
Arm Title
LEEP group
Arm Type
Other
Arm Description
LEEP (loop electrosurgical excision procedure) is one of several possible surgical interventions for treating cervical dysplasia.
Intervention Type
Procedure
Intervention Name(s)
LLETZ
Other Intervention Name(s)
Large Loop Excision of the Transformation Zone
Intervention Description
LLETZ is one of several possible surgical interventions for treating cervical dysplasia. The transformation zone of the cervix is completely removed
Intervention Type
Procedure
Intervention Name(s)
LEEP
Other Intervention Name(s)
Loop Electrosurgical Excision Procedure
Intervention Description
LEEP is one of several possible surgical interventions for treating cervical dysplasia. Only the dysplastic lesion is removed without removing the whole transformation zone.
Primary Outcome Measure Information:
Title
Surgical specimen margin status
Description
Oncological safety as defined by the rate of specimens with involved margins, i.e. cervical dysplasia present at the edge of the surgical specimen.
Time Frame
Pathology assessment of the cone specimen (within 2-4 days after surgery)
Secondary Outcome Measure Information:
Title
Intraoperative and postoperative complication rate
Description
Rate of complications such as excessive bleeding, re-operation, unplanned readmission, infection
Time Frame
During and within 3 weeks after the procedure
Title
Cone size
Description
Size of the resected tissue
Time Frame
During surgery
Title
Patient's pain
Description
Pain experienced by the patients (11-item Visual Analogue Scale); minimum 0 (no pain), maximum 10 (unbearable pain)
Time Frame
Immediately after the surgery
Title
HPV clearance
Description
HPV high-risk positivity by PCR
Time Frame
6 months post surgery
Title
Cone volume
Description
Volume of the resected tissue
Time Frame
During surgery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed High Grade Squamous Intraepithelial Lesion (HSIL) Colposcopically visible lesion No therapy of the disease so far Exclusion Criteria: Pregnancy of the patient at/after inclusion in the study; pregnancy after conization and before the control after 6 months is possible and does not lead to exclusion from the study. Taking immunosuppressive drugs (incl. glucocorticoids) Known HIV positivity Malignant disease requiring treatment Unsatisfactory colposcopy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clemens B Temfper, MD, MBA
Phone
+492323499
Ext
1801
Email
clemens.tempfer@rub.de
First Name & Middle Initial & Last Name or Official Title & Degree
Günther A Rezniczek, PhD
Phone
+492323499
Ext
1058
Email
guenther.rezniczek@rub.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clemens B Tempfer, MD, MBA
Organizational Affiliation
Ruhr-Universität Bochum / Marien Hospital Herne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept. OBGYN Ruhr University Bochum
City
Herne
ZIP/Postal Code
44625
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clemens Tempfer, MD
Phone
+49 2323 499
Ext
1801
Email
clemens.tempfer@marienhospital-herne.de
First Name & Middle Initial & Last Name & Degree
Clemens Tempfer, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24302546
Citation
Martin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2013 Dec 4;2013(12):CD001318. doi: 10.1002/14651858.CD001318.pub3.
Results Reference
background
PubMed Identifier
9234930
Citation
Chua KL, Hjerpe A. Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri. Gynecol Oncol. 1997 Jul;66(1):108-13. doi: 10.1006/gyno.1997.4753.
Results Reference
background

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Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia

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