Trial Title:
Pipelle® Under Ultrasound Guidance (PUG) to Investigate Post-menopausal Bleeding.
NCT ID:
NCT06501846
Condition:
Endometrial Cancer
Post-Menopausal Bleeding
Endometrial Hyperplasia
Conditions: Official terms:
Endometrial Neoplasms
Endometrial Hyperplasia
Uterine Hemorrhage
Hemorrhage
Hyperplasia
Conditions: Keywords:
Pipelle Endometrial Biopsy
Ultrasound Guidance
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomised Controlled Trial
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Pipelle® endometrial biopsy performed under transabdominal ultrasound guidance
Description:
The placement of an ultrasound probe on the lower abdomen while a Pipelle® endometrial
biopsy is obtained.
Arm group label:
Ultrasound Guided Endometrial Biopsy
Intervention type:
Procedure
Intervention name:
Pipelle® endometrial biopsy performed without ultrasound guidance
Description:
A Pipelle® endometrial biopsy is performed by using touch alone.
Arm group label:
Blind Endometrial Biopsy
Summary:
TITLE Pipelle® under Ultrasound Guidance (PUG) to investigate post-menopausal bleeding:
Randomised Controlled Trial
BACKGROUND Women who are suspected of having endometrial cancer (cancer of the inner
lining of the womb) due to vaginal bleeding after the menopause must have a tissue sample
taken from this area to determine whether there is an abnormality.
One method of doing this is by using a small biopsy device (such as a Pipelle®) in the
outpatient setting. This is referred to as an outpatient endometrial biopsy. However, a
significant number of attempted endometrial biopsies are unsuccessful in obtaining a
sample that is adequate for laboratory (histopathological) assessment. When an adequate
sample is not obtained patients must then undergo more invasive testing.
AIM This trial will use an ultrasound probe placed on the lower stomach (transabdominal
ultrasound) to try and guide the doctor performing the endometrial biopsy with the aim of
increasing the number of adequate samples that are obtained.
The trial will also investigate if this technique is less painful and more acceptable to
patients, and if the time taken for patients to receive definitive treatment after their
biopsy is reduced.
ELIGIBILITY All patients presenting with post-menopausal bleeding who have an endometrial
thickness of 5mm or above without a contraindication to an outpatient endometrial biopsy.
DESIGN Prospective randomised controlled trial enrolling 92 patients. When patients are
entered into the study they will randomly assigned to one of two groups. One group will
have their biopsy performed under transabdominal ultrasound guidance and the other will
have the biopsy performed using the traditional 'blind' approach without ultrasound
guidance. There will be 46 patients in each group.
DURATION The trial will run for three years. The trial will be performed in the
outpatient gynaecological oncology department at Queen Charlotte's and Chelsea Hospital,
part of Imperial College Healthcare NHS Trust.
Detailed description:
BACKGROUND Uterine cancer is the most common gynaecological cancer in the United Kingdom
with approximately 9,400 new cases diagnosed each year, over 95% arising from the
endometrium. Almost all endometrial cancers are diagnosed after the menopause, with most
being detected after a woman presents with bleeding. Any woman presenting to her general
practitioner or accident and emergency department with post-menopausal bleeding in the
United Kingdom should receive an urgent two week wait referral to rapid access
gynaecology services. At this appointment women will typically undergo a transvaginal
ultrasound scan to assess the gynaecological anatomy, in particular the endometrium. If
the endometrium is deemed to be thickened, at more than 4 or 5mm depending on local
guidance, sampling is required to rule out endometrial cancer or its precursor,
endometrial hyperplasia.
There are two well established routes for obtaining an endometrial biopsy. These are
'blind' office endometrial sampling and hysteroscopy. If ultrasound has shown any focal
pathology such as an endometrial polyp or a submucosal fibroid, then the patient must
undergo hysteroscopy so this can be directly visualised and confidently removed. Whilst a
highly effective procedure, its primary drawbacks are higher costs, a larger side-effect
profile and potentially greater pain than the alternative, blind office endometrial
sampling.
If a patient has a uniformly thickened endometrium without any suspicion of focal
endometrial pathology they can undergo blind office sampling of the endometrium. This is
performed with a variety of thin, specially designed plastic biopsy devices that obtain
the sample via localised trauma and vacuum suction. This procedure is less invasive,
quicker and simpler to perform than a hysteroscopy, however it has a higher failure rate
with roughly 4 in 10 patient not having an adequate sample obtained. This is due to
either the endometrial sampler not being successfully introduced into the endometrial
cavity, or when successfully introduced, the sample obtained being inadequate for
histopathological assessment. These patients are then committed to a hysteroscopy so
their endometrium can be safely assessed.
PROPOSED STUDY It is theorised that by using ultrasound guidance, the failure rate of
office endometrial biopsies could be reduced. We propose to test in an adequately sized
randomised controlled trial, the hypothesis that Pipelle® (Pipelle de Cornier)
endometrial biopsies, performed under transabdominal ultrasound guidance, will have a
higher success rate than blind biopsies. Potential benefits to patients of positive
findings in this study include a reduced number of investigations, reductions in pain and
increases in patient satisfaction, and a reduction in time from presentation to
definitive treatment.
STUDY DESIGN This will be a single centre, prospective, non-blinded randomised controlled
trial carried out in the outpatient gynaecological oncology department at Queen
Charlotte's and Chelsea Hospital, part of Imperial College Healthcare NHS Trust. The
trial will be carried out by gynaecology doctors of registrar and consultant grade who
are deemed competent in gynaecological ultrasound and endometrial sampling. Both the
doctor and patient will be aware of the study arm allocated. The trial will aim to have
the same number of participants in each arm. The study arms are: (i) Blind Endometrial
Biopsy and (ii) Ultrasound Guided Endometrial Biopsy. 92 patients will be enrolled, with
46 in each arm.
Once randomised and ready for an endometrial biopsy to be performed, those allocated to
the intervention arm will have a transabdominal ultrasound performed by another
gynaecologist in the research team while the Pipelle® biopsy is performed. During the
procedure, the research doctor will, to the best of their ability, ensure the Pipelle® is
introduced to the level of the fundus and that a sample representative of the endometrium
is obtained.
As the patient leaves the clinic room, they will be asked to completed a printed Visual
Analogue Scale questionnaire to assess anxiety, pain during and after the procedure, and
overall patient satisfaction.
The study endpoint will be whichever is the later of: (i) the histopathology for the
final participant being reported with an appropriate management plan made, or (ii) when
the final patient has an attempted Pipelle® endometrial biopsy if this was a failed
attempt.
DATA COLLECTION Demographic patient data collected will include age, BMI, years
post-menopause and parity. Pre-procedural data will record history of gynaecological
surgery including minor procedures, risk factors for endometrial cancer, medical history,
and transvaginal ultrasound scan findings. Intra-procedural data collected for both
groups will record whether access to the endometrial cavity was obtained and if not,
whether this was due to cervical stenosis or other factors. The contents of the Pipelle®
aspiration obtained will be visually assessed by the doctor and if deemed to be an
adequate sample this will be sent on for histopathological assessment. In addition, the
intervention arm will have intra-procedural data collected to assess whether the Pipelle®
was clearly visualised on transabdominal ultrasound and seen at the fundus.
Post-procedural data for both groups will record the number of samples deemed adequate
for assessment by the histopathology department and for those not deemed adequate, the
specified reason. The histology results will be recorded and the proportion of patients
with benign pathology, endometrial hyperplasia (with and without atypia) and endometrial
cancer recorded. Any complications occurring during or post procedure will be recorded.
Patients will be monitored for repeat attendances during the study, to ensure that any
patient later diagnosed with higher order pathology has this recorded.
WITHDRAWAL CRITERIA Patients enrolled in the trial will be free to withdraw consent at
any point without giving reason for doing so. If this occurs their care will be returned
to standard practice. If the doctor performing the procedure feels at any point it is not
safe to proceed, or it is no longer in the patient's best interests, then the procedure
will be abandoned and a discussion had as to how best investigate or treat their
post-menopausal bleeding. Any decision and reason to withdraw from the study will be
recorded.
ASSESSMENT AND FOLLOW-UP Follow up for all trial participants will be the same as for
patients undergoing standard assessment of post-menopausal bleeding. Histopathology
results will be reviewed within two weeks of the sample being taken and if benign the
patient will be discharged from the clinic. Their GP will receive a letter stating that
their investigations are normal and their involvement in the trial has come to an end. If
they have further episodes of post-menopausal bleeding their GP will be asked to refer
them back to the rapid access clinic on a suspected cancer pathway. If non-benign
pathology is found, then the patient will be invited for a further appointment and follow
up will be determined as per the relevant protocol. If the laboratory reports that the
sample taken is not adequate for histopathological analysis the patient will be contacted
and recommended to undergo a hysteroscopy for further assessment.
ETHICS APPROVAL The Study Coordination Centre has obtained approval from the
London-London Bridge Research Ethics Committee (REC) and Health Research Authority (HRA).
The study will be conducted in accordance with the recommendations for physicians
involved in research on human subjects adopted by the 18th World Medical Assembly,
Helsinki 1964 and later revisions.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- All patients with post-menopausal bleeding who require an endometrial biopsy.
Further details:
- Post-menopausal bleeding is defined as bleeding one year after a woman's last
menstrual period or bleeding six months after starting continuous combined hormone
replacement therapy.
- There is no upper age limit, however all patients must be 18 or above.
Strict ultrasound criteria will be followed:
- Endometrium ≥5mm: this is the current cut off used by Imperial College Healthcare
NHS Trust for a biopsy to be indicated in the context of post-menopausal bleeding.
- Smooth, homogenous endometrium with a clearly defined border.
Exclusion Criteria:
- Focal endometrial pathology (including but not limited to endometrial polyps, type
0-2 fibroids, uterine septa and other uterine structural abnormalities).
- Suspicion of non-benign myometrial pathology.
- History of endometrial cancer or endometrial hyperplasia.
- History of cervical cancer.
- Virgo intacta.
- Inability to tolerate vaginal examination.
- Inability to consent.
- The denial or withdrawal of informed written consent.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare Trust
Address:
City:
London
Zip:
W12 0HS
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Joseph Yazbek, MD
Phone:
02033133570
Email:
joseph.yazbek@nhs.net
Contact backup:
Last name:
Nicholas Anson, MBBS
Email:
nicholas.anson@nhs.net
Start date:
July 23, 2024
Completion date:
July 23, 2027
Lead sponsor:
Agency:
Imperial College Healthcare NHS Trust
Agency class:
Other
Source:
Imperial College Healthcare NHS Trust
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06501846
