Efficacy and Safety of Polidocanol Foam 3% in the Treatment of II Degree Hemorrhoidal Disease (SCLEROFOAM)

A Multicentre, Open-label, Single-arm Phase II Trial on the Efficacy and Safety of Sclerotherapy Using 3% Polidocanol Foam to Treat Second-degree Hemorrhoidal Disease

Hemorrhoidal disease (HD) is one of the oldest and most common proctologic diseases that has been described with an estimated prevalence between 4.4% and 86%. Despite the proposal of three mechanisms that might underlie haemorrhoidal development - the varicose vein theory, the vascular hyperplasia theory and the sliding anal-lining theory, the exact pathophysiology of symptomatic hemorrhoid disease is poorly understood. HD seems to be the most common cause for rectal bleeding, or hematochezia, and the second most frequent cause for severe rectorrhagia after diverticulitis. The blood is bright red and coats the stool at the end of defection. Other symptoms include pain, mucous discharge, itching or the sensation of tissue prolapse. The most widely accepted classification is the Goligher classification: Grade I: hemorrhoids bleed but do not prolapse out of the anal canal; Grade II: hemorrhoidal cushions prolapse outside of the anal canal on straining or during bowel movements, but reduce spontaneously; Grade III: hemorrhoidal cushions prolapse outside the anal canal on straining and require manual reduction; Grade IV: hemorrhoidal prolapse is irreducible even with manipulation

As reported by the guidelines of the Italian Society of Colorectal Surgery, in case of failure of conservative therapies the most common outpatient treatments for first- and second-degree Hemorrhoidal Disease (HD) are rubber band ligation and sclerotherapy. Sclerotherapy causes an inflammatory reaction with local sclerosis of the submucosal tissue and a consequent fixation of the haemorrhoidal tissue to the underlying tissue. Moreover, the effect of sclerosing solutions is that of making vascular damage via producing endothelial injury. A 100% improvement in bleeding was reported in patients with II and grade III hemorrhoids, and a complete resolution of the condition was described in 69% of non-selected patients, 52% in grade III and 88% in grade I. Resolution of prolapse was reported in 90-100% of patients affected by grade II hemorrhoids. Complications are rare but serious, and include impotence, irreversible necrotizing fasciitis and abdominal compartment syndrome [31-33]. In Germany, sclerotherapy with liquid agents is considered the first choice in treating grade I hemorrhoids. The only approved medical product by German authorities is polidocanol (Lauromacrogol 400 (INN), H3C-(CH2)11-(O-CH2-CH2)n∼9-OH), produced by Chemische Fabrik Kreussler & Co. GmbH. In Italy, this drug is known as Atossisclerol 3%. The polidocanol is a non-ionic detergent made up of a chain of hydrophilic polyethylene oxide mixed with aliphatic hydrophobic dodecyl alcohol and it is recommended for first- and second-degree HD. The effects of polidocanol are similar to those of phenol oil but less number of side effects. Based on these experiences, Karl-Heinz Moser introduced the use of polidocanol foam in the treatment of grade I hemorrhoids. In 2013, the same author published the results of a randomized, controlled, single blind, multicentre trial on the efficacy and safety of sclerotherapy with polidocanol foam in comparison with liquid sclerosant agents in treating grade I hemorrhoids [28]. In the foam group success rate after one sclerotherapy session was 88%, while success rate among patients treated with liquid polidocanol was 69%. Furthermore, patients treated with foam were more satisfied than those treated with liquid polidocanol (99% vs. 84% p=0.009). Finally, the quantity of polidocanol injected in the foam group was significantly lower (p<0.001), as well as the number of sessions requested (p<0.001). In summary, according to the authors, these results suggest that polidocanol foam can be used as the treatment of choice in grade I HD. The aim of this study is to evaluate the efficacy and safety of sclerotherapy with 3% polidocanol foam (PF) on patients affected by second-degree HD.

Patients enrolled in the study, according to the inclusion and exclusion criteria, will undergo sclerotherapy performed with polidocanol foam (Atossisclerol® 3%, Chemische Fabrik Kreussler & Co. GmbH, Wiesbaden, Germany). The procedure will be performed in the Sims position or lithotomy position. A modified Blonde-Blanchard technique will be adopted, with the tangential injection of polidocanol foam into the submucosa of the apex of each hemorrhoidal pile, without exceeding three piles, and using a self-lighting open-ended anoscope and a 20-G needle in order to reduce bleeding

Patients enrolled in the study, according to the inclusion and exclusion criteria, will undergo sclerotherapy performed with polidocanol foam (Atossisclerol® 3%, Chemische Fabrik Kreussler & Co. GmbH, Wiesbaden, Germany).

The procedure will be performed in the Sims position or lithotomy position. A modified Blonde-Blanchard technique will be adopted, with the tangential injection of polidocanol foam into the submucosa of the apex of each hemorrhoidal pile, without exceeding three piles, and using a self-lighting open-ended anoscope and a 20-G needle in order to reduce bleeding

To establish the success rate after one sclerotherapy session, in terms of complete resolution of bleeding episodes one week after the injection Bleeding will be assessed using both the Hemorrhoidal Disease Symptoms Score and the Giamundo score. Rørvik HD et al (2019) 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; 62:333-342 Giamundo et al (2018) Doppler-guided hemorrhoidal dearterialization with laser (HeLP): a prospective analysis of data from a multicenter trial. Tech Coloproctol; 25:635-643

To establish the success rate in terms of partial or complete resolution of the symptoms Symptoms will be assessed using the Hemorrhoidal Disease Symptom Score described by Rorvik HD

Short Health Scale HD 4 questions with 7-point Liker scale each (1 = very dissatisfied, 7 = very satisfied) Minimum = 4 Maximum = 28

We considered autonomy as the return to normal activity: it includes also the return to work apart from cases of retired patients in which we considered it as the complete return to daily activities

Inclusion Criteria: Patients above 18 and below 75 years of age with a confirmed diagnosis of second-degree HD (proctological examination, proctoscopy and, if required, colonoscopy) Patients who report persistent perianal bleeding as a typical symptom of second-degree HD Informed consent from each patient must be obtained Participating centres will be asked to confirm that they have gained formal approval at their site Exclusion Criteria: Previous anal surgical procedures Previous sclerotherapy or rubber band ligation in the last 12 months Positive pregnancy test Patients with inability to return for postoperative control visits, to sign the informed consent or to fill out the required clinical diary Breast-feeding Known allergy to polidocanol Acute perianal thrombosis Anal fistula Anal fissure Proctitis Fecal incontinence Coagulation disorders Anticoagulant therapy Known HBV, HCV and HIV infection Acite Crohn's disease or Ulcerative colitis Diabetes mellitus I and II COPD Any kind of tumour Previous pelvic radiotherapy

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