Sclerotherapy With Polidocanol Foam In The Treatment Of Hemorrhoidal Disease In Patients With Bleeding Disorders

August 18, 2020 updated by: Paulo Sérgio Durão Salgueiro, Universidade do Porto

Sclerotherapy With Polidocanol Foam In The Management Of First, Second And Third-Grade Hemorrhoidal Disease In Patients With Bleeding Disorders: A Prospective Cohort Study

Treatment of hemorrhoidal disease includes a conservative approach (dietary and behavioral measures, venotropic and topical medication), office-based treatments and surgery. Rubber banding is currently considered the instrumental method of choice in the treatment of hemorrhoidal disease grades I to III (Goligher's classification). However, its use in patients with bleeding disorders is not recommended. Sclerotherapy can be performed in these patients since the hemorrhagic risk is very low. The most commonly used agent for sclerotherapy is liquid polidocanol. Polidocanol foam seems to be more effective than the liquid formulation and is safe in the treatment of hemorrhoidal disease even in patients with coagulation disorders. This study is aimed to evaluate the efficacy and safety of polidocanol foam sclerotherapy in the treatment of hemorrhoidal disease grades I to III in patients with bleeding disorders.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Internal hemorrhoidal disease is classified according to the Goligher classification into grades I, II, III and IV according to its grade of prolapse and reducibility. The treatment of patients should be oriented by the presence of symptoms and the impact on life quality, aspects that are valued on the Sodergren scale.

The hemorrhoidal bleeding, usually mild, may be severe in patients under antithrombotic medications (antiplatelet or anticoagulant) as well as in patients with bleeding disorders non-induced by drugs. With the increase of life expectancy and the high prevalence of atrial fibrillation, the consumption of anticoagulants has also been increasing. Similarly, the use of antiplatelet medication has also increased, especially through its use in the primary and secondary prevention of cardiovascular events. Vitamin K antagonists and antiplatelet drugs are associated with an incidence of digestive bleeding between 1.5% - 4.5% with a short-term mortality of 10-15%. The relation between the use of new oral anticoagulants (NOACs) and digestive bleeding remains a matter of debate, with some studies showing different results when comparing bleeding risk with vitamin K antagonists. Similar to what happen with this subset of patients, those with inherited bleeding disorders are a known subgroup of patients predisposed to hemorrhagic complications. Hemophilia represents the main cause of inherited defects of clotting factors VIII and IX. With the advent of intravenous clotting factors concentrates, the perioperative mortality in this subgroup as decreased in the mid-20th century. However patients with this hematologic disease still have a higher risk of bleeding, delayed wound healing and postoperative infections. To the investigator's knowledge little is known about the prevalence of hemorrhoidal disease in patients with inherited bleeding disorders. Bearing in mind the high rate of surgical complications in these patients, they could represent the ideal candidates for less invasive office-based hemorrhoidal therapy. Instrumental, office-based treatment is reserved for internal hemorrhoidal disease grades I to III. Regardless of the applied technique, the goal is to decrease vascularization, decrease hemorrhoidal volume and increase the fixation of the fibrovascular pedicle to the rectal wall, thus treating the bleeding and hemorrhoidal prolapse. Rubber band ligation is considered the method of choice in the treatment of hemorrhoidal disease. However, its use is associated to bleeding rates after procedure ranging between 3.5 - 50% and late bleeding rates between 13% - 18,3% that may occur until 7-14 days after treatment. The hemorrhagic event is significant in 0.8% of cases and may even prove fatal. For this reason, this technique is contraindicated in patients with bleeding disorders. In patients on antithrombotic medication, discontinuation of this medication is recommended for 7 days before the ligation procedure and 7-10 days after the procedure, which substantially increases the risk of cardioembolic events. In contrast, sclerotherapy is a technique with a low rate of bleeding complications and can be used to treat hemorrhoidal disease grades I to III. After intravascular injection of sclerosing agent above the pectineal line - Blanchard technique - an inflammatory and fibrotic response is obtained that interrupts the blood supply. Although there are multiple sclerosing agents, in Portugal, the most frequently used is liquid polidocanol. As a nonionic detergent its use as a foam (obtained by the technique of Tessari which uses a device that combines two syringes and a three-way tap in which the polidocanol is mixed with air under mechanical force) appears to be associated with greater efficacy even with lower doses of sclerosing agent. Sclerotherapy with liquid polidocanol is effective in the treatment of grade I hemorrhoidal disease with a study demonstrating superiority of foam formulation in this grade of hemorrhoidal disease. A recently published Portuguese study sought to study the efficacy and safety of foamed polidocanol sclerotherapy in patients with grade I to IV hemorrhoidal disease. On the findings, which included 2000 participants, 210 of them on anticoagulant and/or dual antiplatelet therapy, the authors conclude that this instrumental procedure is effective and safe even in patients on antithrombotic therapy. However, no comparison was made between the incidence of complications occurred in this subgroup of patients with the remaining patients without antithrombotic therapy. As far as we know there are no published studies comparing polidocanol foam sclerotherapy to other ablative techniques.

The investigators are conducting a multicentric longitudinal prospective study including adult patients, with or without bleeding disorders, with hemorrhoidal disease grades I to III submitted to polidocanol foam sclerotherapy in three health institutions during an inclusion period of 1.5 years. Efficacy is assessed using Sodergren score of symptoms, bleeding and Goligher grades, and recurrence during follow-up. For the safety evaluation, complications are recorded. Efficacy and safety outcomes will be compared between two groups of patients: with bleeding disorders (Group A) and without bleeding disorders (Group B).

Study Type

Interventional

Enrollment (Anticipated)

150

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
      • Amadora, Portugal, 2720-276
        • Hospital Prof. Doutor Fernando da Fonseca, EPE
      • Guimarães, Portugal, 4800-000
        • Hospital Senhora da Oliveira
      • 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Participants will be recruited from August 1st, 2018 until February 1st, 2020.

Inclusion Criteria:

  • Adult patients with symptomatic internal hemorrhoidal disease grades I to III submitted to sclerotherapy with polidocanol foam in three Portuguese health institutions (Centro Hospitalar Universitário do Porto, Hospital Senhora da Oliveira - Guimarães and Hospital Prof. Doutor Fernando da Fonseca, EPE - Amadora);
  • Hemorrhoidal disease refractory to conservative therapy (dietary modification, intestinal transit modifiers, topical and venotropic drugs) during a period no less than 4 weeks;

Exclusion Criteria:

  • Known allergy to polidocanol;
  • Liver cirrhosis;
  • Pregnant or lactating women;
  • Inflammatory bowel disease;
  • Other concomitant symptomatic perianal disease;
  • History of office-based or surgical treatment of hemorrhoidal disease in the last 6 months;
  • Immunosuppression.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Polidocanol foam sclerotherapy

During the intervention period the participants are observed at 3-week intervals (maximum of 3 sessions).

The required number of polidocanol foam sclerotherapy sessions (maximum of 3) is determined by clinical and anoscopic evaluation (if the participant is non-symptomatic and/or there is no significant hemorrhoidal disease on anoscopy, the patient will not be a candidate for additional instrumental therapy moving directly to the follow-up period). After each session all patients were instructed to adopt dietary measures and adequate hydration maintaining therapy with systemic venotropic, topical and laxative if necessary.

After the intervention period, a one-year follow-up is scheduled with medical appointments performed every 3 months.
Procedure: Polidocanol foam sclerotherapy
  • Preparation of the foam is done according to the Tessari technique (2 disposable 20ml syringe, a three-way tap, reusable extender adapted to intravenous needle).
  • Sclerosant applied according to the Blanchard technique through a disposable transparent anoscope (patient in knee-chest position).
  • In each session, treatment can be performed on more than one hemorrhoidal cushion. The maximum dose per treatment session is 20ml (mixture of 4ml of polidocanol 3% with 16ml of air).
  • During the intervention period the participants are observed at 3-week intervals. The required number of sessions (maximum of 3) is determined by clinical and anoscopic evaluation.
  • After the intervention period, a one-year follow-up is scheduled with medical appointments performed every 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness evaluation (therapeutic success)
Time Frame: 3 months

For efficacy evaluation during the intervention period the outcomes will be compared between groups A and B.

Therapeutic success is a compound variable of Sodergren symptom score and bleeding grade and is subdivided in:

  • Complete (Sodergren score = 0 and bleeding grade ≤ 1);
  • Partial (Sodergren score> 0 and bleeding grade> 1 but with improvement over initial score); - Therapeutic failure (participants that, after 3 sessions of office-based treatment worsened or maintained the initial Sodergren score and bleeding grade).
3 months
Safety evaluationL occurrence of complications
Time Frame: 12 months

Comparison of the occurrence of complications in both groups A and B.

Complications are classified as:

  • Mild (e.g. pain/discomfort, minor bleeding, external hemorrhoidal thrombosis not requiring surgical intervention);
  • Moderate (e.g. external hemorrhoidal thrombosis requiring surgical intervention, moderate bleeding not requiring blood transfusion, urgent hemostasis or urgent surgery);
  • Severe (e.g. sepsis, Fournier's gangrene, perineal abscess, bleeding with hemodynamic instability, transfusional need or urgent surgery, sexual impotence in man).
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness evaluation (Goligher classification)
Time Frame: 3 months

For efficacy evaluation during the intervention period the outcomes will be compared between groups A and B.

Variation of Goligher classification before and after the intervention.
3 months
Effectiveness evaluation (number of office-based sessions)
Time Frame: 3 months
Number of office-based therapy sessions and polidocanol foam dose applied during the intervention period (comparing groups A and B).
3 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)

August 1, 2018

Primary Completion (Actual)

February 1, 2020

Study Completion (Anticipated)

February 1, 2021

Study Registration Dates

First Submitted

December 2, 2019

First Submitted That Met QC Criteria

December 4, 2019

First Posted (Actual)

December 5, 2019

Study Record Updates

Last Update Posted (Actual)

August 19, 2020

Last Update Submitted That Met QC Criteria

August 18, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12422301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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