Polidocanol Foam in Hemorrhoidal Disease in Patients With Liver Cirrhosis

Liver Cirrhosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05807425
• Other study ID #: 2021.051(041-DEFI/042-CE)
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 31, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: April 2023
• Source: Universidade do Porto
• Contact: Paulo Salgueiro, MD PhD
• Phone: 00351222077500
• Email: paulosalgueiro[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Hemorrhoids
• Liver Cirrhosis

Intervention

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).

Locations

Country	Name	City	State
Portugal	Centro Hospitalar Universitário do Porto	Porto

Sponsors (1)

Lead Sponsor	Collaborator
Universidade do Porto

Country where clinical trial is conducted

Portugal, 

References & Publications (15)

Awad AE, Soliman HH, Saif SA, Darwish AM, Mosaad S, Elfert AA. A prospective randomised comparative study of endoscopic band ligation versus injection sclerotherapy of bleeding internal haemorrhoids in patients with liver cirrhosis. Arab J Gastroenterol. 2012 Jun;13(2):77-81. doi: 10.1016/j.ajg.2012.03.008. Epub 2012 Apr 24. — View Citation

Camus M, Khungar V, Jensen DM, Ohning GV, Kovacs TO, Jutabha R, Ghassemi KA, Machicado GA, Dulai GS. Origin, Clinical Characteristics and 30-Day Outcomes of Severe Hematochezia in Cirrhotics and Non-cirrhotics. Dig Dis Sci. 2016 Sep;61(9):2732-40. doi: 10.1007/s10620-016-4198-y. Epub 2016 Jun 10. — View Citation

Fernandes V, Fonseca J. Polidocanol Foam Injected at High Doses with Intravenous Needle: The (Almost) Perfect Treatment of Symptomatic Internal Hemorrhoids. GE Port J Gastroenterol. 2019 May;26(3):169-175. doi: 10.1159/000492202. Epub 2018 Aug 31. — View Citation

Hosking SW, Smart HL, Johnson AG, Triger DR. Anorectal varices, haemorrhoids, and portal hypertension. Lancet. 1989 Feb 18;1(8634):349-52. doi: 10.1016/s0140-6736(89)91724-8. — View Citation

Huang WS, Lin PY, Chin CC, Yeh CH, Hsieh CC, Chang TS, Wang JY. Stapled hemorrhoidopexy for prolapsed hemorrhoids in patients with liver cirrhosis; a preliminary outcome for 8-case experience. Int J Colorectal Dis. 2007 Sep;22(9):1083-9. doi: 10.1007/s00384-007-0271-5. Epub 2007 Mar 2. — View Citation

Hull TL. Surgery of the anus, rectum and colon. Gastroenterology. 2000 Oct;119(4):1173-5. doi: 10.1016/s0016-5085(00)80038-4. No abstract available. — View Citation

Jacobs DM, Bubrick MP, Onstad GR, Hitchcock CR. The relationship of hemorrhoids to portal hypertension. Dis Colon Rectum. 1980 Nov-Dec;23(8):567-9. doi: 10.1007/BF02988998. — View Citation

Misra SP, Dwivedi M, Misra V. Prevalence and factors influencing hemorrhoids, anorectal varices, and colopathy in patients with portal hypertension. Endoscopy. 1996 May;28(4):340-5. doi: 10.1055/s-2007-1005477. — View Citation

Neves S, Falcao D, Povo A, Castro-Pocas F, Oliveira J, Salgueiro P. 3% polidocanol foam sclerotherapy versus hemorrhoidal artery ligation with recto anal repair in hemorrhoidal disease grades II-III: a randomized, pilot trial. Rev Esp Enferm Dig. 2023 Mar;115(3):115-120. doi: 10.17235/reed.2022.8568/2022. — View Citation

Riss S, Weiser FA, Schwameis K, Riss T, Mittlbock M, Steiner G, Stift A. The prevalence of hemorrhoids in adults. Int J Colorectal Dis. 2012 Feb;27(2):215-20. doi: 10.1007/s00384-011-1316-3. Epub 2011 Sep 20. — View Citation

Rorvik HD, Styr K, Ilum L, McKinstry GL, Dragesund T, Campos AH, Brandstrup B, Olaison G. Hemorrhoidal Disease Symptom Score and Short Health ScaleHD: New Tools to Evaluate Symptoms and Health-Related Quality of Life in Hemorrhoidal Disease. Dis Colon Rectum. 2019 Mar;62(3):333-342. doi: 10.1097/DCR.0000000000001234. — View Citation

Salgueiro P, Caetano AC, Oliveira AM, Rosa B, Mascarenhas-Saraiva M, Ministro P, Amaro P, Godinho R, Coelho R, Gaio R, Fernandes S, Fernandes V, Castro-Pocas F. Portuguese Society of Gastroenterology Consensus on the Diagnosis and Management of Hemorrhoidal Disease. GE Port J Gastroenterol. 2020 Feb;27(2):90-102. doi: 10.1159/000502260. Epub 2019 Sep 5. — View Citation

Salgueiro P, Garrido M, Santos RG, Pedroto I, Castro-Pocas FM. Polidocanol Foam Sclerotherapy Versus Rubber Band Ligation in Hemorrhoidal Disease Grades I/II/III: Randomized Trial. Dis Colon Rectum. 2022 Jul 1;65(7):e718-e727. doi: 10.1097/DCR.0000000000002117. Epub 2022 Nov 22. — View Citation

Salgueiro P, Ramos MI, Castro-Pocas F, Libanio D. Office-Based Procedures in the Management of Hemorrhoidal Disease: Rubber Band Ligation versus Sclerotherapy - Systematic Review and Meta-Analysis. GE Port J Gastroenterol. 2022 Mar 8;29(6):409-419. doi: 10.1159/000522171. eCollection 2022 Nov. — View Citation

Salgueiro P, Rei A, Garrido M, Rosa B, Oliveira AM, Pereira-Guedes T, Morais S, Castro-Pocas F. Polidocanol foam sclerotherapy in the treatment of hemorrhoidal disease in patients with bleeding disorders: a multicenter, prospective, cohort study. Tech Coloproctol. 2022 Aug;26(8):615-625. doi: 10.1007/s10151-022-02600-5. Epub 2022 Feb 25. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Therapeutic success	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	9 weeks
Primary	Incidence of Treatment Adverse Events	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).	9 weeks
Secondary	Variation of Goligher classification (hemorrhoidal prolapse from grade 1 to grade 4)	Variation of Goligher classification before and after the intervention	9 weeks
Secondary	Number of office-based therapy sessions	Number of office-based therapy sessions performed during intervention period	9 weeks
Secondary	Hemorrhoidal disease recurrence	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.	1 year