Large Loop Excision of the Transformation Zone (LLETZ) With vs Without IntraOperative Application of Lugol's Iodine

NCT05132114 | Completed

• 1 other identifier: LLETZ-IOLI-1
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

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 gynecologist's preventive smear test 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, if necessary, surgically removed. Conization (= surgical removal of a cone of tissue from the cervix) is the method of choice for removing the diseased tissue. LLETZ conization (Large Loop Excision of the Transformation Zone) is the worldwide standard surgical procedure for conization. There is risk of local persistence of the precancerous lesion if the cervical dysplasia is not completely removed. To minimize this, the iodine test can be used. Here, a 5% iodine solution (so-called Lugol's solution) is dabbed onto the cervix uteri, resulting in an intense and characteristic brown staining of the healthy cervical epithelium. Sites without staining are termed iodine negative and may contain dysplastic cells. The strength of iodine testing lies in its high specificity, i.e., the reliable ability to exclude false-positive results. The purpose of intraoperative iodine staining is to select the resection line with a high degree of certainty in healthy (i.e., iodine-positive) tissue in order to reduce the rate of cervical dysplasia that is not completely removed (so-called non-in-sano resection, or R1 resection). Systematic survey data from the dysplasia units certified in Germany on the question of the use of intraoperative iodine testing in Germany are lacking, as is the literature as a whole. For example, the current S3 guideline of the German Society of Gynecology and Obstetrics on the diagnosis and treatment of cervical dysplasia (as of March 2020) names intraoperative iodine testing only as a possible option for performing LLETZ. In this prospective, randomized study, the investigators aim to answer the question whether LLETZ performed with the help of an iodine test with selection of the resection line in the iodine-positive area leads to a lower rate of R1 resections compared to the standard LLETZ without iodine test.

Conditions

Cervical Dysplasia

Keywords

cervical dyslasia; LLETZ; LEEP; Lugol's iodine; conization

Outcome Measures

Primary Outcomes (1)

• Rate of R1 resections

  The primary outcome parameter is the rate of R1 resections, defined as the presence of a CIN I, CIN II, or CIN III at the ectocervical and/or endocervical resection margin, as indicated in the histopathologic report.

  Specimen from surgery (result expected 1-2 days after surgery)

Secondary Outcomes (7)

• Cone mass

  During surgery, immediately after the excision

• Procedure duration

  At surgery

• Rate of complications

  During surgery up to 14 days post surgery

• Surgeon's rating of handling

  Immediately after surgery

• Surgeon's satisfaction

  Immediately after surgery

Study Arms (2)

Control Group

NO INTERVENTION

LLETZ (without intraoperative Lugol's iodine)

Iodine group

EXPERIMENTAL

LLETZ after the intraoperative application of Lugol's iodine

Diagnostic Test: Lugol's iodine test

Interventions

Lugol's iodine test DIAGNOSTIC_TEST

Intraoperative application of Lugol's iodine (i.e. staining of the cervix with Lugol's iodine solution)

Iodine group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written consent
• Colposcopy performed preoperatively
• Histologically (by previously performed colposcopy) confirmed dysplasia (CIN 1, CIN 2 or CIN 3)
• Age \>18 years

You may not qualify if:

• Pregnant patients
• Patients with insufficient knowledge of the German language
• Treatments already performed on the cervix uteri, in particular conization
• Blood coagulation disorders
• Taking blood thinning substances
• Iodine allergy

Sponsors & Collaborators

• Ruhr University of Bochum: lead

Study Sites (1)

Marien Hospital Herne

Herne, North Rhine-Westphalia, 44625, Germany

Location

Related Publications (13)

• Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187. doi: 10.15585/mmwr.rr7004a1.

  PMID: 34292926 BACKGROUND

• Chesson HW, Dunne EF, Hariri S, Markowitz LE. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014 Nov;41(11):660-4. doi: 10.1097/OLQ.0000000000000193.

  PMID: 25299412 BACKGROUND

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Mathevet P, Chemali E, Roy M, Dargent D. Long-term outcome of a randomized study comparing three techniques of conization: cold knife, laser, and LEEP. Eur J Obstet Gynecol Reprod Biol. 2003 Feb 10;106(2):214-8. doi: 10.1016/s0301-2115(02)00245-2.

  PMID: 12551795 BACKGROUND

• Bevis KS, Biggio JR. Cervical conization and the risk of preterm delivery. Am J Obstet Gynecol. 2011 Jul;205(1):19-27. doi: 10.1016/j.ajog.2011.01.003. Epub 2011 Feb 23.

  PMID: 21345402 BACKGROUND

• Jin G, LanLan Z, Li C, Dan Z. Pregnancy outcome following loop electrosurgical excision procedure (LEEP) a systematic review and meta-analysis. Arch Gynecol Obstet. 2014 Jan;289(1):85-99. doi: 10.1007/s00404-013-2955-0. Epub 2013 Jul 11.

  PMID: 23843155 BACKGROUND

• Khalid S, Dimitriou E, Conroy R, Paraskevaidis E, Kyrgiou M, Harrity C, Arbyn M, Prendiville W. The thickness and volume of LLETZ specimens can predict the relative risk of pregnancy-related morbidity. BJOG. 2012 May;119(6):685-91. doi: 10.1111/j.1471-0528.2011.03252.x. Epub 2012 Feb 14.

  PMID: 22329499 BACKGROUND

• Shaco-Levy R, Eger G, Dreiher J, Benharroch D, Meirovitz M. Positive margin status in uterine cervix cone specimens is associated with persistent/recurrent high-grade dysplasia. Int J Gynecol Pathol. 2014 Jan;33(1):83-8. doi: 10.1097/PGP.0b013e3182763158.

  PMID: 24300540 BACKGROUND

• Preaubert L, Gondry J, Mancini J, Chevreau J, Lamblin G, Atallah A, Lavoue V, Caradec C, Baldauf JJ, Bryand A, Henno S, Villeret J, Agostini A, Douvier S, Jarniat A, Riethmuller D, Mendel A, Brun JL, Rakotomahenina H, Carcopino X. Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study. J Low Genit Tract Dis. 2016 Jan;20(1):15-21. doi: 10.1097/LGT.0000000000000156.

  PMID: 26704328 BACKGROUND

• Kuhn W. [Colposcopy in the diagnosis of early cervical cancer]. Pathologe. 2011 Nov;32(6):497-504. doi: 10.1007/s00292-011-1480-9. German.

  PMID: 21984389 BACKGROUND

• Hilal Z, Rezniczek GA, Alici F, Kumpernatz A, Dogan A, Alieva L, Tempfer CB. Loop electrosurgical excision procedure with or without intraoperative colposcopy: a randomized trial. Am J Obstet Gynecol. 2018 Oct;219(4):377.e1-377.e7. doi: 10.1016/j.ajog.2018.07.023. Epub 2018 Jul 29.

  PMID: 30063903 BACKGROUND

• Rezniczek GA, Hecken JM, Rehman S, Dogan A, Tempfer CB, Hilal Z. Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial. Am J Obstet Gynecol. 2020 Dec;223(6):888.e1-888.e9. doi: 10.1016/j.ajog.2020.06.041. Epub 2020 Jul 24.

  PMID: 32585223 BACKGROUND

• Hilal Z, Rezniczek GA, El-Fizazi N, Tempfer CB. Large Loop Excision of the Transformation Zone Versus True Cone Biopsy Electrode Excision: A Randomized Trial. J Low Genit Tract Dis. 2017 Oct;21(4):272-278. doi: 10.1097/LGT.0000000000000329.

  PMID: 28953118 BACKGROUND

Related Links

• German S3 Guidelines

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Clemens B Tempfer, MD, MBA

  Ruhr-Universität Bochum / Marien Hospital Herne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are not aware of their treatment allocation in order not to influence patient reported outcomes
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Obstetrics and Gynecologiy

Model Details: Prospective randomized trial with 2 groups (use vs not use of Lugol's iodine during LLETZ)

Study Record Dates

• First Submitted: November 11, 2021
• First Posted: November 24, 2021
• Study Start: January 17, 2022
• Primary Completion: September 25, 2025
• Study Completion: October 16, 2025
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: After publication of the study results, no time limit.
• Access Criteria: Reasonable request, approval of the intended study by an independent review committee identified for this purpose.

Locations

DE (1)