Polidocanol Foam VS Artery Ligation in Hemorrhoidal Disease

February 5, 2021 updated by: Paulo Sérgio Durão Salgueiro, Universidade do Porto

Sclerotherapy With Polidocanol Foam Versus Hemorrhoidal Artery Ligation With Recto Anal Repair in the Treatment of Second and Third-grade Hemorrhoidal Disease: a Prospective Study

Background: Hemorrhoidal disease is extremely frequent in the adult population and, as a benign pathology, the treatment should be guided by the patient's symptoms. Treatment of hemorrhoidal disease includes a conservative approach, office-based treatments and surgery.

This study is aimed to evaluate and compare the efficacy and safety of the treatment of hemorrhoidal disease with non-surgical office-based method polidocanol foam sclerotherapy (SP) and the surgical technique doppler-guided hemorrhoidal artery ligation with recto-anal repair.

Methods: Prospective, unicentric study including patients with symptomatic hemorrhoidal disease grade II and III refractory to conservative therapy, submitted either to SP (n=24) or to HAL-RAR procedure (n=21), during a recruitment period of 6 months.

Patients were evaluated for efficacy (Sodergren's scale of symptoms and severity of bleeding) and safety (complications and implication in personal and professional life), up to one month after treatment. In follow-up period (6 months) participants were evaluated for hemorrhoidal disease recurrence.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

INTRODUCTION:

Instrumental office-based procedures are usually indicated for internal hemorrhoidal disease grade I and II which are refractory to conservative medical treatments and in selected cases of grade III hemorrhoidal disease. Despite being invasive, these techniques are more conservative than surgical treatments and are also effective. The primary goals are to decrease the amount of redundant tissue, reduce vascularity, and affix the hemorrhoidal cushions to minimize prolapse. Office-based procedures include rubber band ligation (RBL), sclerotherapy (liquid and foam agents), infrared photocoagulation, cryotherapy, radiofrequency ablation among others.

Hemorrhoidal sclerosis is a procedure indicated to treat grade I and II hemorrhoidal disease. It has also been used in the treatment of internal grade III hemorrhoidal disease, but there are limited data on its efficacy. Performed through an anoscope and according to Blanchard technique, internal hemorrhoids are located and injected with a sclerosant material into the submucosa at the base of the hemorrhoid, above the anterolateral line. The sclerosant subsequently causes an inflammatory response and fibrosis that interrupts the vascular blood supply. A variety of sclerosants have been used including ethanolamine, quinine, hypertonic saline, aluminum potassium sulfate and tannic acid (ALTA), and 5% phenol in oil. Recently, a new sclerosing agent, polidocanol, started to be employed in the treatment of hemorrhoidal disease. It is a nonionic detergent and consists of a hydrophilic polyethylene oxide chain combined with hydrophobic aliphatic dodecyl alcohol. When injected into varicose veins, polidocanol damages the endothelium of blood vessels, allowing platelets to aggregate. Eventually, a dense network of platelets, cellular debris, and fibrin occludes the vessel, which is subsequently replaced with connective fibrous tissue. In addition to the treatment of hemorrhoidal disease, polidocanol is used for sclerotherapy of varicose veins of the lower extremities and for the treatment of esophageal varices. The advantages of this sclerosing agent include a highly satisfactory efficiency, a low necrotic potential, and a good general tolerance. At the same time, it has a local anesthetic effect which permits almost painless sclerotherapy. Nevertheless, its use is contraindicated in patients with acute thromboembolic diseases and in those with allergy to the drug. Polidocanol can be used in its liquid or foam form. It has been proved the foam formulation allows for greater efficacy, since it requires lower doses of sclerosant agent. This is because the sclerotic effect is maximized by increasing the contact surface area with varices walls. This foam is previously prepared according to the Tessari's method, in which two 10 mL syringes are connected by a 3-way stopcock. The syringes contain air and a sclerosing agent (3% polydocanol), with a ratio of 4:1, respectively, and twenty passages from one syringe to the other are made in order to obtain a sclerosing foam. Several studies reported the efficacy of the use of sclerotherapy with liquid polidocanol in hemorrhoidal disease. Specifically for the treatment of grade I hemorrhoids, there is one study showing the superiority of polidocanol foam compared to its liquid formulation. However, there's a lack of research about its use in hemorrhoidal disease other than grade I. The most common complications of sclerotherapy include minor discomfort or bleeding. Although it is a very safe treatment option, some serious side effects, including erectile dysfunction and urinary retention, have been reported. The proper injection technique of sclerosant is essential to avoid complications such as mucosal ulceration or necrosis, prostatic abscess and retroperitoneal sepsis. Sclerotherapy is a valid alternative when conservative therapy has failed. Moreover, this procedure can also be used for the treatment of patients whose hemorrhage is the main symptom, for patients on antithrombotic medication, as well as cirrhotic and immunocompromised patients.

Surgical treatment is reserved for refractory cases to nonsurgical approaches, grade IV or mixed hemorrhoidal disease (internal and external components), symptomatic hemorrhoidal disease with concomitant anorectal pathology and lastly if it's the patient's choice. Although surgical approach is apparently more effective than instrumental treatment, it is also associated with substantial postsurgical morbidity, particularly postoperative pain and limitation in day-life activities. Several surgical methods have been described including open and closed hemorrhoidectomy, doppler guided hemorrhoidal artery ligation (HAL) and hemorrhoidectomy stapler. The choice of each method should consider the grade of hemorrhoidal disease and the predominant symptoms of the patient, together with the experience of the center.

HAL technique involves the use of Doppler ultrasound and a specialized anoscope. The principles include the use of a Doppler probe to identify the six main feeding arteries within the anal canal and their ligation with absorbable suture above the dentate line, therefore associated with less pain. Finally, plication of redundant hemorrhoidal mucosa is performed (if there is hemorrhoidal or muco-hemorrhoidal prolapse), known as recto-anal-repair (RAR), mucopexy or hemorrhoidopexy. The aim of this recent surgical procedure is to treat patients' symptoms without tissue destruction. Early results of HAL were promising, with lower pain scores than hemorrhoidectomy, and relief of bleeding and tissue prolapse in over 90% of patients. Since then, several randomized clinical trials have been performed with mixed results. Currently, HAL remains a viable approach to multicolumn internal hemorrhoids. However, the short-term benefits regarding postoperative pain have recently not been as remarkable as in the earlier studies. Also, there has been a progressive increase in long term recurrence rates, especially for grade III and IV hemorrhoids.

Some studies have been conducted with the purpose of comparing the efficacy of nonsurgical office-based treatments with surgical ones.

A multicentric, open-label, randomized controlled trial, compared RBL and HAL, revealing higher efficacy of the surgical procedure. If, however, RBL is considered a course of treatment involving repeat banding, the procedures are equally effective. Besides, HAL was proved to be more painful than RBL. Another study comparing infrared photocoagulation with HAL showed that both procedures are minimally invasive and associated with minimal discomfort, but HAL is more effective than infrared photocoagulation in controlling symptoms of hemorrhoids. There has been no comparative studies between polidocanol foam sclerotherapy and hemorrhoidal artery ligation, to date.

Therefore, the purpose of the present study is to evaluate and compare the safety and efficacy of the treatment of hemorrhoidal disease with polidocanol foam sclerotherapy and HAL-RAR.

METHODS:

Prospective, unicentric study (Centro Hospitalar Universitário do Porto) which is aimed to compare the efficacy and safety of the treatment techniques in patients with hemorrhoidal disease grade II and III.

Patients referred were randomly allocated to one of the two treatments considered in this study (SP and HAL-RAR).

All participants should have had prior endoscopic study, at least sigmoidoscopy, or total colonoscopy if they were older than 50 years or younger, with a family history of colorectal cancer, colon adenomas, or suspected inflammatory bowel disease.

Only patients who agreed to informed consent were included, after a clear explanation of the type of study and the intervention that was going to be made.

In screening visits, demographic and anthropometric data (such as age, sex, weight and height, education and employment status) were collected, as well as grade of hemorrhoidal disease. Baseline questionnaires were used to assess Sodergren's scale of symptoms and the severity of bleeding.

Informed consent and an information brochure, explaining the study and adequate dietary and behavioral care, were provided. Additionally, all participants were given a direct contact for any doubts and notification of complications, in which case additional observation should be made.

When office-based treatment was performed, an intervention period was considered, in which patients were observed at 3-week intervals (the required number of sessions, maximum of 3, depended on the clinical response - if 3 weeks after the previous treatment, the participant scored zero points in the Sodergren scale and had a hemorrhage grade ≤1, he was not a candidate for additional instrumental therapy.).

Surgical treatment was performed only once. One month after this intervention period, Sodergren's scale of symptoms and severity of bleeding were reevaluated. In addition, complications registry, and implication in personal and professional life, measured in number of work-loss days, if applied, were also assessed. Patients was followed-up every 3 months for total of 6 months for evaluation of hemorrhoidal disease symptoms recurrence.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Portugal
      • Porto, Portugal, 4050-000
        • Centro Hospitalar Universitario do Porto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients older than 18 years with symptomatic hemorrhoidal disease grade II and III (Goligher's classification)
  • Refractory to conservative therapy (dietary modification, intestinal transit modifiers, topical and phlebotonic medications) for a period of not less than 4 weeks

Exclusion Criteria:

  • Cirrhosis
  • Pregnant or breast-feeding women
  • Known allergy to polidocanol
  • Another perianal disease that can cause symptoms similar to hemorrhoidal disease
  • Colorectal malignancy
  • Concomitant presence of external hemorrhoidal disease and/or hemorrhoidal thrombosis - - Office or surgical treatment for hemorrhoids within 6 months prior to inclusion
  • Antiplatelet or hypocoagulant medication
  • Hematological disorders
  • Immunosuppressive states
  • Inflammatory bowel disease
  • Patients unable to have general or spinal anesthetic

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Polidocanol foam sclerotherapy
Patients submitted to polidocanol foam sclerotherapy
Drug: Polidocanol foam sclerotherapy

i. Patients underwent preparation, two hours before the intervention, with cleaning enema (Disodium phosphate). No antibiotic prophylaxis was prescribed.

ii. Preparation of the polidocanol (Aethoxysklerol 3%) foam according to Tessari technique immediately before application, so that the "microbubbles" of the foam did not disintegrate; iii. The procedure was performed in the medical office. Application according to the Blanchard technique through a disposable transparent anoscope, in jackknife position, using a 20mL disposable syringe of the mixture (polidocanol + air) and a reusable 10 cm syringe extender adapted to an intravenous needle; iv. Patients were treated in a maximum of 3 sessions, at 3 weeks intervals; v. Maximum dose per treatment session of 20mL of mixture of 4mL of polidocanol 3% with 16mL of air; i. In each session, the sclerosant was injected in one or more hemorroidary cushion;

Other Names:
  • Aethoxysklerol 3%)
Active Comparator: Doppler-guided hemorrhoidal artery ligation
Patients submitted to doppler-guided hemorrhoidal artery ligation
Procedure: Doppler-guided hemorrhoidal artery ligation

i. Patients underwent preparation with cleaning enema (Disodium phosphate). No antibiotic prophylaxis was prescribed.

ii. The procedure was performed in the operating room of an outpatient surgery unit, under regional anestesia.

iii. A proctoscope with a Doppler transducer in its tip was introduced inside the anal canal to search for the superior rectal artery.

iv. Each branch was ligated with suture above the dentate line. The device was rotated slowly in clockwise direction to locate further arteries at that level.

v. Rectoanal repair consisted in a continuous running suture was applied longitudinally just over every prolapsed hemorrhoid.

Other Names:
  • HAL-RAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapeutic success
Time Frame: 3 months

Efficacy indicator composed by Sodergren score and bleeding grade:

  • Complete (Sodergren score = 0 and bleeding grade <= 1);
  • Partial (Sodergren score > 0 and bleeding grade > 1 but, at least, one of them with improvement, regarding the initial score, and none of them worse);
  • Therapeutic failure (participants that, one month after the last instrumental treatment or one month after surgery, worsened or maintained the initial Sodergren score and bleeding grade);
3 months
Safety evaluation
Time Frame: 3 Months

Record of complications resulting from the therapy:

  • Mild (e.g. pain/discomfort, pruritus, bleeding grade 1)
  • Moderate (e.g., external hemorrhoidal thrombosis, bleeding without hemodynamic instability, no blood transfusion, no need for haemostasis or urgent surgery): do not endanger the patient's life or leave long term sequelae;
  • Severe (e.g. sepsis, Fournier's gangrene, perineal abscess, bleeding with hemodynamic instability, transfusional need or urgent surgery, sexual impotence in man): they put the patient's life at risk.
3 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Professional life implications
Time Frame: 3 months
Implications in professional life were measured in number of work-loss days
3 months
Personal life implications
Time Frame: 3 months
Outcome assessed with some simple yes-no questions (eg: personal and family relationships, sexual activity, physical exercise, social and civic activities), and if at least one of them was answered affirmatively, we considered treatment had significant impact in patient's personal life.
3 months
Number of treatment sessions
Time Frame: 3 months
Number of instrumental treatment sessions required
3 months
Recurrence
Time Frame: 6 Months
Evaluation of symptoms recurrence during de follow-up period
6 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidade do Porto

Investigators

  • Principal Investigator: Paulo Salgueiro, MD, Centro Hospitalar Universitario do Porto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2019

Primary Completion (Actual)

February 1, 2020

Study Completion (Actual)

March 25, 2020

Study Registration Dates

First Submitted

December 14, 2020

First Submitted That Met QC Criteria

December 14, 2020

First Posted (Actual)

December 19, 2020

Study Record Updates

Last Update Posted (Actual)

February 10, 2021

Last Update Submitted That Met QC Criteria

February 5, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 514741899

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Study data can shared upon justified request

IPD Sharing Time Frame

Upon request

IPD Sharing Access Criteria

Justified request (investigation, meta-analysis, medical education)

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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