Polidocanol Foam in Hemorrhoidal Disease in Patients With Liver Cirrhosis

Sponsor

Universidade do Porto (Other)

Overall Status

Recruiting

CT.gov ID

NCT05807425

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hemorrhoidal disease (HD) is a common health problem, affecting up to 38,9% of adult population. HD is also a common finding in up to 36% of cirrhotic patients, as hemorrhoidal plexus is a possible site of portosystemic venous anastomosis. Cirrhotic patients represent a group often neglected in clinical trials so, little is known about the optimal treatment for HD these patients. The objective of this study is to prospectively evaluate the efficacy and safety of treatment of grade I, II and III internal HD with polidocanol foam in cirrhotic patients.

Condition or Disease	Intervention/Treatment	Phase
Hemorrhoids Liver Cirrhosis	Procedure: Polidocanol foam sclerotherapy	Phase 2/Phase 3

Detailed Description

Hemorrhoidal disease (HD) is a common health problem, affecting up to 38,9% of adult population. Despite being a benign condition, associated symptoms like bleeding, pain, prolapsing, swelling, itching, and mucus soiling impact considerably on patients' quality of life. HD is also a common finding in up to 36% of cirrhotic patients, as hemorrhoidal plexus is a possible site of portosystemic venous anastomosis. Despite portal hypertension does not increase the prevalence of hemorrhoids, elevated portal venous pressure, with a not so rare contribution of coagulopathy, may result in massive, life-threatening hemorrhoidal bleeding, unlike the normal population. Besides, internal HD bleeding is the most frequently identified cause of bleeding with origin on the lower gastrointestinal tract among cirrhotic patients with severe hematochezia .

HD treatment can be grouped into conservative (diet, lifestyle changes, laxatives, anti-inflammatory drugs, phlebotonics), office-based (sclerotherapy, ligation, photocoagulation, laser photocoagulation, among others) and surgical (hemorrhoidectomy, hemorrhoidopexy). The choice of therapy should be oriented by the Goligher's classification, or a symptom score such as Rørvik's Hemorrhoidal Disease Symptom Score (HDSS).

Cirrhotic patients represent a group often neglected in clinical trials so, little is known about the optimal treatment for HD these patients. Surgical treatment with stapled hemorrhoidopexy has been described in cirrhotic patients as a feasible and safe approach, but with up to 46,7% of the procedures complicated with postoperative staple-line bleeding, although all of them managed with conservative treatment without reoperation or death. Recently, Ashraf et al compared hemorrhoidectomy performed using rubber band ligation (RBL) with conventional hemorrhoidectomy in 40 randomized patients with liver disease and diagnosed with grade I, II, or III HD. Intraoperative blood loss was lower in RBL group (1.2 ± 1.6 ml vs 22.2 ± 6.58 ml, p=0,001), as well as operative time (9.00 ± 2.449 min vs 24.100 ± 3.669 min, p=0,001). Importantly, postoperative pain (35% vs 100%, p=0,001), bleeding (15% vs 45%, p=0,022) and urine retention (20% vs 55%, p=0,011) were lower in the RBL group, along with time of hospital stay (8.6 ± 2.54 h vs 60.65 ± 41.93, p=0,002) and time of wound healing (16.85 ± 1.87 days vs 31.00 ± 3.57 days, p=0,003).

Bearing in mind the high rate of surgical complications in cirrhotic patients, these results suggest that office-based treatments, may be the preferred treatment for cirrhotic patients with HD grades I to III. Awad et al, compared the efficacy of endoscopic injection sclerotherapy (EIS) to RBL in the treatment of bleeding internal hemorrhoids in 120 adult patients with liver cirrhosis. Both techniques were highly effective in the control of bleeding with a low rebleeding [10% in the EBL group and 13.33% in the EIS group] and recurrence [20% in the EBL group and 20% in the EIS group] rates; also, EBL had significantly less pain and higher patient satisfaction than EIS. However, these authors have used liquid sclerosing agents (either ethanolamine oleate 5% or N-butyl cyanoacrylate). A recent portuguese study by Fernandes et al has evaluated the efficacy and safety of a sclerosing agent, polidocanol, foam injection in 2000 consecutive patients with prolapsed hemorrhoids (grades II/III/IV). This technique showed high efficacy (98%) and tolerability (92% with mild/no pain) with only 0,7% of serious complications (major bleeding n=3; urinary retention n=4; infection/suppuration requiring surgery n=2). Also, in this cohort, 210 patients (10,5%) were under anticoagulation or double antiplatelet therapy) and only 2 of these patients presented clinically significant bleeding. The authors conclude that polidocanol foam should be used as first-line treatment of most hemorrhoid patient, including those under anticoagulation and antiplatelet therapy. Nevertheless, no cirrhotic patients were included, so results cannot be generalized to this particular high-risk group.

The objective of this study is to prospectively evaluate the efficacy and safety of treatment of grade I, II and III internal hemorrhoidal disease with polidocanol foam in cirrhotic patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

During the intervention period the participants are observed at 3-week intervals (maximum of 3 sessions). The required number of 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 the intervention period, a one-year follow-up is scheduled with medical appointments performed every 3 months.During the intervention period the participants are observed at 3-week intervals (maximum of 3 sessions). The required number of 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 the intervention period, a one-year follow-up is scheduled with medical appointments performed every 3 months.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sclerotherapy With Polidocanol Foam in the Treatment of First, Second and Third-Grade Hemorrhoidal Disease in Patients With Liver Cirrhosis: A Prospective, Cohort Trial

Actual Study Start Date :

Mar 31, 2023

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Polidocanol foam sclerotherapy A cohort of cirrhotic patients with hemorrhoidal disease will be treated with polidocanol foam sclerotherapy.	Procedure: Polidocanol foam sclerotherapy The preparation of the foam is done according to the Tessari's technique using 2 disposable 20ml syringe, a three-way tap and a 10cm reusable extender adapted to intravenous needle. The sclerosant is applied according to the Blanchard's technique through a disposable transparent anoscope with the patient in jack-knife (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).

Arm

Intervention/Treatment

Experimental: Polidocanol foam sclerotherapy

A cohort of cirrhotic patients with hemorrhoidal disease will be treated with polidocanol foam sclerotherapy.

Procedure: Polidocanol foam sclerotherapy

The preparation of the foam is done according to the Tessari's technique using 2 disposable 20ml syringe, a three-way tap and a 10cm reusable extender adapted to intravenous needle. The sclerosant is applied according to the Blanchard's technique through a disposable transparent anoscope with the patient in jack-knife (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).

Outcome Measures

Primary Outcome Measures

Therapeutic success [9 weeks]
For efficacy evaluation during the intervention period the outcome of therapeutic success (improvement of HDSS) will be assessed; the therapeutic success is subdivided in: complete (HDSS = 0), partial (HDSS > 0 but with improvement over the initial score) or unsuccess (participants that, after 3 sessions of office-based treatment worsened or maintained the initial HDSS
Incidence of Treatment Adverse Events [9 weeks]
Complications will be assessed and 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); and severe (e.g. sepsis, Fournier's gangrene, perineal abscess, bleeding with hemodynamic instability, transfusion need or urgent surgery, sexual impotence in man).

Secondary Outcome Measures

Variation of Goligher classification (hemorrhoidal prolapse from grade 1 to grade 4) [9 weeks]
Variation of Goligher classification before and after the intervention
Number of office-based therapy sessions [9 weeks]
Number of office-based therapy sessions performed during intervention period
Hemorrhoidal disease recurrence [1 year]
Recurrence during the follow-up period (for patients who have had therapeutic success) will be defined as mild, if HDSS worsened compared to the previous visit but is still better than the initial visit; or severe if HDSS equals or worsens compared to the initial score, requiring instrumental or surgical treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients with liver cirrhosis and symptomatic HD grades I to III
Refractory to conservative therapy (dietary modification, intestinal transit modifiers, topical and phlebotonics), during a period of 4 weeks

Exclusion Criteria:

Known allergy to polidocanol
Pregnant and 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