Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03402282 |
| Other study ID # |
72364117.0.1001.0071 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 6, 2018 |
| Est. completion date |
October 1, 2021 |
Study information
| Verified date |
August 2021 |
| Source |
Hospital Israelita Albert Einstein |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hemorrhoidal disease diagnosis is based on medical history combined with physical exam and
complementary exam. Physical exam should include inspection at exertion, digital rectal exam
,and anoscopy.
The treatment indicated in patients with hemorrhoidal disease varies according to the disease
grade, and it may be clinical or surgical. The classic surgical approach is an open surgical
correction , a technique that has high success rates and low recurrence rates; however, it is
accompanied by intense pain.
Based on the concept that hemorrhoids are formed by pathological changes in submucosal pads
vascularization in anal channel transition zone, selective embolization of upper rectal
artery branches were performed in 14 patients with long-term severe rectal bleeding secondary
to hemorrhoidal disease by Vidal et al. with no pain or ischemic symptoms being seen.
- Main Objective To determine the feasibility of implementing upper rectal artery
embolization in the treatment of patients with grade 2 (protrude beyond the anal verge
with straining or defecating but reduce spontaneously) and 3 hemorrhoids (protrude
spontaneously or with straining and require manual reduction), relating its short- and
long-term outcomes with patients undergoing surgical repair through the classic
technique
- Hypothesis The expectation is that, with upper rectal artery embolization, patients
experience a decrease or remission of symptoms, such as bleeding, pain and symptoms
related to hemorrhoidal pads edema. Another expectation is that the decrease in the
number of days to return to daily activities
Description:
Proposal description 1.1. Hemorrhoids: Epidemiology, Clinical Presentation and Diagnostic
Assessment: In the normal anal channel, there are three highly-vascularized areas (pads),
forming slight masses in the submucosa made of blood vessels, smooth muscle and elastic and
connective tissue, and are located at the left lateral, right anterior and right posterior
quadrants, and contribute in anal continence . The term hemorrhoids refers to clinical
situations where these hypervascularized pads are abnormal and cause clinical symptoms.
The exact disease prevalence of symptomatic hemorrhoidal disease is difficult to establish,
since many symptomatic patients do not seek an assessment, while others assign varied
anorectal symptoms as being resulting from hemorrhoids. Some series estimate prevalence
between 4 and 40 %. Although many patients will exhibit symptomatic hemorrhoids along life,
the peak incidence occurs between 45 and 65 years old and its development prior to 20 years
old is rarely frequent . Among the factors related to a higher risk of developing the disease
are: pregnancy, white race, females.
Hemorrhoids may be divided as external and internal. External hemorrhoids are covered by
anoderm (richly enervated layer), are located distally to the dentate line and their main
symptoms are edema, causing discomfort and difficult local hygiene, which may also exhibit an
intense pain when thrombosed. Internal hemorrhoids are located proximally to the dentate line
and are lined with poorly enervated anorectal mucosa, and rarely cause pain, except when
thrombosed and combined with prolapse and necrosis; often their symptoms are prolapse and
bleeding.
Internal hemorrhoids may be subdivided into 4 grades: grade 1 are defined by a protuberance
in anal channel and may show prolapse beyond the dentate line at great exertion; grade 2 are
hemorrhoids prolapsing beyond the dentate line at exertion, but reduced spontaneously; grade
3 are hemorrhoids prolapsing beyond the dentate line, requiring manual reduction; and grade 4
are defined by non-reducing prolapsed hemorrhoids, being at risk of strangulation.
Hemorrhoidal disease diagnosis is based on medical history combined with physical exam and
complementary exam. Physical exam should include inspection at exertion, digital rectal exam
(which allows an assessment of internal and external hemorrhoids, anal channel tonus
assessment, in addition to excluding other diseases, such as neoplasm and sphincter spasm)
and anoscopy. Among complementary tests, flexible rectal sigmoidoscopy, colonoscopy, barium
enema may be requested at complementary diagnosis, mainly to rule out other diseases.
1.2. Hemorrhoids: conventional treatment: non-surgical and surgical
The treatment indicated in patients with hemorrhoidal disease varies according to the disease
grade, and it may be clinical or surgical. Non-surgical management is indicated for patients
with internal and external hemorrhoids (grade 1 to 4) and consists in better local hygiene,
avoiding excessive exertion and improving food habits (including more fibers in the diet),
combined or not with laxative drugs. Patients with prolapsed external or internal hemorrhoids
may further benefit from the combination of clinical measures and more invasive measures such
as rubber band ligation, sclerotherapy and electrocoagulation.
Surgical management is best indicated in patients failing clinical measures and patients with
grade 3 and 4 hemorrhoids, and is indicated in about 10% of cases . The classic surgical
approach is an open surgical correction through Milligan and Morgan technique, which
comprised resection and ligation as high as possible of the three arterial pedicles feeding
the hemorrhoids, a technique that has high success rates and low recurrence rates; however,
it is accompanied by intense pain ( with pain scale in the first 24 hours of approximately
6.1 ± 1.5; in the first evacuation 4.5 ± 1.5) and a prolonged recovery period to return to
normal activities (6.95 ± 3.6 days). Currently, two less invasive new techniques with less
intense post-operative pain were proposed: anopexy with circular stapler (Longo's technique-
which consists of interrupting the superior rectal branches and resecting the rectal mucosal
ring, it is less invasive, but not free from complications which may range from urinary
retention (1.9 to 5%) rectal-vaginal fistulae, bleedings requiring blood transfusion (1.5 a
9%), external hemorrhoidal thrombosis (1.2 a 4.7%) and perforations) and Doppler-guided
elective ligation of hemorrhoidal artery through endoanal access ; however, these have a
recurrence higher than 10% and complications from 6 to 22% of cases such as: bleeding,
urinary retention, hematoma in the submucosa, fissure, abscess. Both techniques are
associated with reduction of arterial flow with subsequent reduction of hemorrhoids .
1.3. Hemorrhoids: Hemorrhoidal Artery Embolization
Based on the concept that hemorrhoids are formed by pathological changes in submucosal pads
vascularization in anal channel transition zone, Galkin in 1994 reported the first cases of
treating hemorrhoidal disease through embolization of upper hemorrhoidal branches in 34
patients, without recurrence after 24 months of follow-up.
Recently, Vidal et al 2014 describe the "emborrhoid" technique, consisting in super selective
embolization of upper rectal artery branches. "Emborrhoid" technique was performed through
right common femoral artery puncture (inserting a 5Fr introducer) and catheterization of
lower mesenteric artery with a Simmons catheter, followed by a super selective
catheterization of lower rectal arteries with a microcatheter and embolization with Nester
0.018 coils with 2 and 3 mm of diameter and 3-cm long. This technique was performed in 14
patients with long-term severe rectal bleeding secondary to hemorrhoidal disease grades 2 (10
patients), 3 (3 patients) and 4 (1 patient) who were not candidates to other clinical or
surgical therapies after a multidisciplinary discussion . The technical success was seen in a
100% of cases. After a follow-up between 2 and 13 months, clinical success (no bleeding or
minimum bleeding and well tolerated by the patient) occurred in 72% (10/14) of cases, with no
pain or ischemic symptoms being seen. Four patients experienced new bleeding, of these, 2
underwent a new embolization and 2 refused further treatment.
Moussa et al performed upper rectal arteries embolization with the "emborrhoid" technique
described by Vidal et al in 30 patients with hemorrhoidal disease and an immediate technical
success was observed in 93% of cases, with no pain in the postoperative period and absence of
complications related to puncture site or ischemic, such as rectal ulceration, anal fissure.
1.3.1. Complications Related to Conventional Surgical Treatment The possible early
complications related to conventional surgical treatments are pain, urinary retention
(2-36%), intestinal constipation, bleeding (0.03- 6%) and infection (0.5-5.5%). And the late
complications may include anal incontinence (flatulence and / or stools- 2-12%) and anal
stenosis (0-6%).
1.3.2 Complications Related to Upper Rectal Artery Embolization: The possible complications
related to upper rectal artery embolization relate to the puncture site and potential rectal
ischemia. However, with the use of coils, this risk is decreased, since it does not cause
distal embolization, as per Vidal et al, who reported 14 cases of coil embolization at upper
rectal arteries, with no rectal ischemia symptoms seen.
2. Study Objectives: Main Objective To determine the feasibility of implementing upper rectal
artery embolization in the treatment of patients with grade 2 (protrude beyond the anal verge
with straining or defecating but reduce spontaneously) and 3 hemorrhoids (protrude
spontaneously or with straining and require manual reduction), relating its short- and
long-term outcomes with patients undergoing surgical repair through the classic technique
(Milligan and Morgan technique).
Hypothesis The expectation is that, with upper rectal artery embolization, patients
experience a decrease or remission of symptoms, such as bleeding, pain and symptoms related
to hemorrhoidal pads edema. Another expectation is that the decrease in the number of days to
return to daily activities.
3. Materials and Methods This project will be developed by using the "Emborrhoid" technique
described by Vidal et al. , consisting in upper rectal artery embolization with coils for
patients with hemorrhoidal disease exhibiting chronic bleeding, and it has been shown to be
safe and efficient .
This research project will be developed together with the Hospital Israelita Albert Einstein
- Morumbi Unit and the Vila Santa Catarina Municipal Hospital, with patients recruited from
grade 2 and 3 hemorrhoidal disease patients requiring surgical treatment referred to Hospital
Vila Santa Catarina-Hospital Israelita Albert Einstein who accept to take part in the
research protocol. Patients will undergo a detailed clinical and proctological evaluation, in
addition to colonoscopy, and will then be assigned to 2 groups with 20 patients each
(embolization or conventional surgical treatment groups) in a random way. Patients assigned
to embolization group will be referred to the hemodynamics department of Hospital Israelita
Albert Einstein - Morumbi Unit to undergo upper hemorrhoidal artery embolization, by an
experienced interventional radiology team (>5 years of experience) and patients assigned to
conventional surgical treatment group will be treated at Hospital Vila Santa Catarina by an
experienced proctologists team (> 10 years of experience).
Follow-up will be performed with visits at post-operative days 7 and 30 , as well as
telephone calls at 1, 3, 6, and 12 months. Patients will fill out a questionnaire at home
during the first week, to evaluate their pain symptoms through the Visual Analogue Scale, at
the following moments: first evacuation, first and third days, and report the number and
number of times it was necessary to use analgesic and/or anti-inflammatory medication.
3.2. Inclusion Criteria Male and female patients aged above 18 years old, with internal
and/or external hemorrhoids experiencing clinical symptoms (anemia, persistent / recurrent
bleeding hemorrhoidal source> 3 months, episodes of recurrent hemorrhoidal thrombosis (> 2
episodes) or associated the symptoms of hemorrhoidal disease) with surgical indication and
contraindication of band ligation and / or photocoagulation infrared accepting the items
pointed in the informed consent form.
3.3. Exclusion Criteria Patients with contraindications for angiogram performance (allergy to
intravenous contrast), patients with aortic atherosclerosis (femoral pulse and difference
Doppler angiography or with stenosis 20%) patients in the daily use of NSAIDs or weak opioids
or who refuse to take part in this project will be excluded from this study.
3.4. Study Dynamics Patients from conventional surgical treatment group will undergo the
standard treatment for hemorrhoidal disease at Hospital Vila Santa Catarina and patients from
embolization group will be referred to Hospital Israelita Albert Einstein, where they will
undergo pelvic angiogram, assessing possible anatomical variations, followed by a super
selective catheterization of upper rectal artery branches and coil embolization of these
branches, followed by a controlled pelvic angiography and compression for 30 minutes of the
puncture site after the end of the procedure. After the procedure, the rates of technical
success and early and intermediate-term clinical success will be assessed, as well as
potential complications.
3.5. Sample Calculation Based on the literature, the expected value of pain given by the
visual analogue scale on the first 10 days of surgery was 4.2 in patients submitted to
hemorrhoidectomy using the classic Milligan-Morgan technique, with the variability of 2.24
(DP = 2,24 pontos) . It is expected patients who underwent the procedure present a maximum of
2 points at pain scale in the same period. With an 80% of power and 95% confidence - it's
only required 20 subjects for the study.
3.6. Randomization Allocation of patients in the 2 groups will be performed through
randomization, in blocks consisting of 4 individuals in each block, in order to reduce the
variability and potential confounding between the 2 groups.
4. Informed Consent
All patients should be given informed consents
5. Ethical Considerations 5.1. Declaration of Helsinki
The participating researcher will ensure that this program will be conducted in full
compliance with the Helsinki Declaration and all local and national regulations.
5.2. Safety
5.2.1 Adverse Events and Complications Graduation Criteria Adverse events and complications
were classified according to the terminology criteria of the National Institutes of Health
(NIH) (4.0; edition 28.05.2009 version).
5.2.2. DSMB - Data Safety Monitoring Board The primary safety result of the study (local
complications of puncture site and rectal ischemia) will be reviewed by an independent Data
Safety Monitoring Board, composed of at least one general surgeon / proctologist and one
interventional vascular radiologist. In locu analyzes will be performed at every 10 patients
submitted to treatment (according to the randomization of the groups). The meeting will be
programmed according to the recruitment and will be schedule with the inclusion of 1/4, 1/2,
3/4 of the participants (10 participants, 20 participants, 30 participants respectively)
6. Confidentiality of data The team involved in the study pledges to keep under
confidentiality all the information here displayed as well as use the data only for the
specific purposes of this study.
