Clinical trial NCT04188171: Sclerotherapy With Polidocanol Foam In The Treatment Of Hemorrhoidal Disease In Patients With Bleeding Disorders
Official title: Sclerotherapy With Polidocanol Foam In The Management Of First, Second And Third-Grade Hemorrhoidal Disease In Patients With Bleeding Disorders: A Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Hemorrhoids
Bleeding Disorder
Keywords: Sclerotherapy
Polidocanol foam
Hemorrhoidal disease
Lead sponsor: Universidade do Porto
Sponsor class: OTHER
First posted: 2019-12-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 and safety outcomes will be compared between two groups of patients: with bleeding disorders (Group A) and without bleeding disorders (Group B).
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Effectiveness evaluation (therapeutic success)
timeFrame: 3 months
measure: Safety evaluationL occurrence of complications
timeFrame: 12 months
Secondary outcomes:
measure: Effectiveness evaluation (Goligher classification)
timeFrame: 3 months
measure: Effectiveness evaluation (number of office-based sessions)
timeFrame: 3 months
Other outcomes:
Locations:
city: Amadora
country: Portugal
facility: Hospital Prof. Doutor Fernando da Fonseca, EPE
city: Guimarães
country: Portugal
facility: Hospital Senhora da Oliveira
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto
Study officials:
affiliation: Centro Hospitalar Universitário do Porto
name: Paulo Salgueiro, MD
role: PRINCIPAL_INVESTIGATOR
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