Trial Title:
DEFLAGYN® Vaginal Gel and Spontaneous Remission and Regression of Unclear Cervical Smears and HPV High-risk Infections
NCT ID:
NCT05509413
Condition:
Cervix Dysplasia
HPV Infection
Conditions: Official terms:
Infections
Communicable Diseases
Papillomavirus Infections
Uterine Cervical Dysplasia
Remission, Spontaneous
Conditions: Keywords:
cervical dysplasia
unclear cytology
HPV infection
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
1:1 randomization into a control arm (wait-and-see) and a treatment arm (vaginal gel)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
DEFLAGYN vaginal gel
Description:
DEFLAGYN is a vaginal gel, classified as a medical device, containing silica and citric
acid, which binds pathogens, inhibits their spread and exerts an antioxidant effect. It
is applied intravaginally (through an applicator) and used for 3 months.
Arm group label:
DEFLAGYN Arm
Summary:
Human papillomaviruses (HPV) are the most common sexually transmitted pathogens worldwide
and in most cases are causally associated with the development of cervical cancer, one of
the most common cancers in women and one of the leading causes of death in women
worldwide. Precancerous lesions (dysplasias) or the presence of a high-risk HPV subtype
are detected by a screening smear test performed by a gynecologist. If precancerous
lesions are detected, conization (= surgical removal of a cone of tissue from the cervix)
is the method of choice for removing the diseased tissue. However, if the degree of
dysplasia is correspondingly low or the smear is unclear, then the guideline-compliant
non-surgical treatment provides for a wait-and-see approach with PAP and HPV smear
control after 6-8 months.
This "wait-and-see" approach can be complemented by local therapy with an
immunostimulant. For this purpose, DEFLAGYN® (a vaginal gel containing silica and citric
acid) and Aldara® (imiquimod, a Toll-Like Re-ceptor 7 antagonist) are available. However,
while the latter is not approved for the treatment of cervical dysplasia or HPV
infection, DEFLAGYN® has CE marking and approval as a medical device for treatment in a
number of indications, such as unclear cervical smears, HPV-induced cervical lesions,
p16/Ki-67-positive cervical lesions or cervical erosions.
However, available studies on the efficacy of DEFLAGYN are limited. For example, there is
only one prospective randomized trial (Major et al, 2021, Arch. Gynecol. Obstet.
303:501-511), which included 216 women with histologically confirmed CIN 1/2. A 3-month
intravaginal application of DEFLAGYN® resulted in regression of CIN 1/2 in 72% versus 25%
in the control arm (no intervention). Side effects of therapy with DEFLAGYN® were not
observed in this study.
Due to the frequency of CIN and HPV infections in the female population and due to the
high medical relevance of a conservative method of treating this disease, further
methodologically high-quality studies on the efficacy of DEFLAGYN® should be performed.
Detailed description:
1. HPV and dysplasia of the cervix uteri Human papillomaviruses (HPV) are the most
common sexually transmitted pathogens worldwide. The prevalence in both male and
female populations is high. Epidemiological estimates suggest that 85-91% of
sexually active adults acquire at least one genital HPV infection by age 50, with
approximately 95% of HPV infections being spontaneously eliminated within 2 years in
terms of HPV immunologic clearance. HPV preferentially infects the epithelial cells
of the anogenital area and, through incorporation of HPV DNA into the host genome of
the basal cells of the squamous epithelium of the cervix and subsequent expression
of viral components, causes dysplastic changes in the cervical epithelium that, if
left untreated, can develop into invasive carcinoma of the cervix (cervical
carcinoma).
Cervical carcinoma is the fourth most common cancer as well as the fourth leading
cause of cancer-related death in women worldwide, responsible for 6.6% (570,000) of
all new cancer cases and 7.5% (311,000) of cancer-related deaths in women in 2018.
The precursor of squamous cell carcinoma of the uterine cervix (approximately 80% of
all cervical cancers) is cervical intraepithelial neoplasia (CIN), which has three
grades of expression (CIN1, CIN 2, and CIN 3). Compared with invasive cervical
carcinoma, the incidence and prevalence of precancerous lesions of the cervix uteri
are much higher. It is estimated that approximately 100,00 w0omen in Germany develop
high-grade dysplasia (CIN2/CIN3) each year.
2. Therapy Dysplasia of the cervix typically becomes conspicuous during gynecological
screening examinations. Here, smears are taken from the ectocervix and endocervix
and assessed cytologically for dysplastic cells and the quality of the smear after
Papanicolaou staining. HPV infection diagnostics are also performed as part of the
statutory cervical carcinoma screening (annually or every 3 years) in order to
detect the presence of HPV high risk infections.
In case of abnormalities in the cervical smear and/or HPV high risk infection with
suspicion of cervical dysplasia, presentation to a specialized dysplasia
consultation is recommended for further clarification of dysplastic changes. During
the subsequent colposcopic examination, a histological tissue sample ('cervical
biopsy') of conspicuous areas is taken. The histopathological processing of the
tissue samples and the colposcopic image of the spread of the changes in the cervix
then allow individualized therapy planning.
3. Conization as the standard of surgical treatment If precancerous lesions with the
potential to develop into an invasive cervical tumor are detected, conization (=
surgical removal of a cone of tissue from the cervix) is the method of choice for
removing the diseased tissue. The worldwide standard surgical procedure for
conization is LLETZ conization (="Large Loop Excision of the Transformation Zone").
In addition to the risk of local persistence of precancerous lesions if cervical
dysplasia is incompletely removed, LLETZ also increases the risk of preterm delivery
in subsequent pregnancy. This risk increases with increasing volume of removed
tissue. To reduce or avoid the aforementioned complications, conization should be
performed under colposcopic vision and as little healthy cervical tissue as possible
should be removed.
4. Non-surgical treatment options Non-surgical methods for the treatment of CIN and/or
HPV high risk infections are limited. According to the current S3 guideline, in case
of CIN 1 and/or HPV high risk infection, a wait-and-see approach with PAP and HPV
smear control in 6-8 months is possible. Alternatively, local therapy with an
immunostimulant may be used. DEFLAGYN® and Aldara® are available for this purpose.
Aldara® is imiquimod, a Toll-Like Receptor 7 (TLR 7) antagonist, which leads to a
local immune response. However, Aldara® is not approved for the treatment of CIN or
HPV infections. DEFLAGYN®, on the other hand, has a CE mark and medical device
approval for the treatment of unclear cervical smears (ASC-US, ASC-H, LSIL, HSIL or
PAP II-p, PAP III-p, PAP IIID1, PAP IIID2 or PAP III, PAP IIID) or HPV-induced
cervical lesions or p16/Ki-67-positive cervical lesions or cervical erosions.
5. DEFLAGYN® - Mode of action and approval status DEFLAGYN® is a vaginal gel containing
silica and citric acid, which binds pathogens, inhibits their spread and exerts an
antioxidant effect. It is applied intravaginally and used for 3 months. In a
prospective randomized study of 216 women with histologically confirmed CIN 1/2, 3
months of intravaginal application of DEFLAGYN® resulted in regression of CIN 1/2 in
72% versus 25% in the control arm (no intervention). The rate of HPV high risk
infections decreased from 87% to 44% in the intervention arm. No other intervention
studies on the efficacy of DEFLAGYN® can be found in the literature (PubMed search
on 08/14/2022; search terms: dysplasia, deflagyn, HPV, silicon dioxide gel,
randomized). Side effects of therapy with DEFLAGYN® were not observed in the study.
Due to the frequency of CIN and HPV infections in the female population and due to
the high medical relevance of a conservative method of this disease, further
methodologically high-quality studies on the efficacy of DEFLAGYN® are useful.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written consent
- Unclear cervical smear (ASC-US, ASC-H, LSIL, HSIL or PAP II-p, PAP III-p, PAP IIID1,
PAP IIID2 (Munich III) or PAP III, PAP IIID, PAP I + HPV high-risk infection)
Exclusion Criteria:
- Pregnancy
- Known hypersensitivity to any of the ingredients of the vaginal gel
- Insufficient knowledge of the German language
- Pre-existing oncological diseases
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Marien Hospital Herne
Address:
City:
Herne
Zip:
44625
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Clemens B Tempfer, MD, MBA
Phone:
+49 2323 499
Phone ext:
1801
Email:
clemens.tempfer@rub.de
Contact backup:
Last name:
Günther A Rezniczek, PhD
Phone:
+49 2323 499
Phone ext:
1058
Email:
guenther.rezniczek@rub.de
Start date:
November 8, 2022
Completion date:
February 2025
Lead sponsor:
Agency:
Ruhr University of Bochum
Agency class:
Other
Source:
Ruhr University of Bochum
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05509413
https://www.leitlinienprogramm-onkologie.de/leitlinien/zervixkarzinom-praevention/
