Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. A clinical trial of hydroxyethylrutosides in the treatment of haemorrhoids of pregnancy. Experimental comparative study of the efficacy and side effects of Cissus quadrangularis L. (Vitaceae) to Daflon (Servier) and placebo in the treatment of acute hemorrhoids. The impact of micronized purified flavonoid fraction on the treatment of acute haemorrhoidal episodes. Daflon 500 mg in the treatment of hemorrhoidal disease: a demonstrated efficacy in comparison with placebo. Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status: a randomized, double-blind, placebo-controlled, phase IV study. Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial. [Treatment of acute symptoms of hemorrhoid disease with high-dose oral O-(beta-hydroxyethyl)-rutosides]. Prospective, randomized, controlled, observer-blinded trial of combined infrared photocoagulation and micronized purified flavonoid fraction versus each alone for the treatment of hemorrhoidal disease. How we can improve patients' comfort after Milligan-Morgan open haemorrhoidectomy. Double-blind, randomized clinical trial of troxerutin-carbazochrome in patients with hemorrhoids. Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Pycnogenol treatment of acute hemorrhoidal episodes. Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorrhoidectomy. Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Efficacy of calcium dobesilate in treating acute attacks of hemorrhoidal disease. Flavonoids to reduce bleeding and pain after stapled hemorrhoidopexy: a randomized controlled trial.
One hundred patients with a history of hemorrhoidal disease and suffering from an acute hemorrhoidal attack were randomized into two parallel groups and treated with Daflon 500 mg* (D500) or placebo (PL) under double-blind conditions. Daflon 500 mg was administered at the dosage of three tablets bid the first four days and two tablets bid the following three days. Overall improvement of symptoms was greater in the D500 group than in the PL group, from D2 up to D7. The clinical severity of proctorrhagia, anal discomfort, pain, and anal discharge diminished in both groups but to a greater extent in the D500 group (P < 0.001 for all parameters except protorrhagia, P = 0.006). Inflammation, congestion, edema, and prolapse were more markedly improved in the D500 group than in the PL group. Duration and severity of the current hemorrhoidal episode, as assessed by patient self-evaluation, were less important in the D500 group as compared with previous episodes. Use of analgesics and topical medications diminished in both groups, with a major reduction in the D500 group from D4 (P < 0.001). Acceptability was good in both groups: no patient experienced major side effects. In summary, treatment with D500 resulted in a quicker and more pronounced relief of signs and symptoms of acute hemorrhoids than with the placebo. The safety and efficacy of 500 mg O-(beta-hydroxyethyl)rutosides given orally twice daily in the treatment of 97 patients with first-, second-, or third-degree haemorrhoids were investigated in a double-blind, randomized placebo-controlled trial. The rutosides produced a significant (P less than 0.001) improvement in patient-assessed subjective symptoms (pain, bleeding, exudation and pruritus) compared with placebo. There was also a significant (P less than 0.001) improvement in clinician-assessed subjective and objective signs (bleeding, inflammation and dilatation of the haemorrhoidal plexus) after 2 and 4 weeks' treatment compared with placebo. There were three mild, transient side-effects reported in the active treatment group and no drug-related problems in the pregnancy or delivery were observed. The results suggest that O-(beta-hydroxyethyl)rutosides provide a safe and effective treatment for women with haemorrhoids of pregnancy. To investigate efficacy and side effects of Cissus quadrangularis L. and micronised purified flavanoid fraction (MPFF) in treatment of hemorrhoids.
                A prospective double blind randomized study was designed in acute hemorrhoidal patients from three hospitals. In each hospital, eighty patients received the flavanoid mixture, C. quadrangularis, or placebo (3 x 2 p.c. for 4 days and then 2 x 2 p.c. for 3 days). Patients were evaluated on bleeding, pain, discharge, pruritis, erythema, and direct patient interviews. Each symptom was scored on a graded severity scale from 0 to 3 on the first day and the seventh day. Blood tests and monitoring of treatment-related side effects were conducted.
                Five hundred seventy patients (299 females, 271 males) were enrolled. No significant difference regarding age, gender, occupation, and history of disease was recorded. Mostly acute bleeding ceased at the second day in all groups. Analysis on all groups revealed improvement in all symptoms with non-significant difference. No adverse events, no blood chemistry changes were reported.
                The therapeutic efficacy of flavanoid mixture, C. quadrangularis L. and placebo are not different indicating that they play no role in improving early hemorrhoidal symptoms. Long-term studies should be conducted for effects in preventive and curative action. To evaluate the efficacy and the tolerability of micronized purified flavonoid fraction (MPFF) on symptoms and signs of acute haemorrhoidal disease (HD).
                Patients experiencing an acute HD episode for less than 48 h were enrolled in this randomized, double-blind, placebo-controlled study (n = 90 in two hospital-based study centres in Beijing). One group received MPFF, six tablets per day for 4 days followed by four tablets per day for 3 days and the other a placebo. Symptoms and signs of HD were assessed by blinded observers at day 0 (D0), day 4 (D4), and day 7 (D7) on a 4-point severity grading scale (from 1 = absent to 4 = severe). A two-way variance analysis was performed for comparison between groups.
                Forty-nine patients (49) in the MPFF group and 41 in the placebo group (mean age 43.2 years [range 18-76 years]), percentage of male gender 54.4%, mean time from onset of acute episode 45.3 h (range 16-48 h) were included in this analysis. No significant differences between groups were seen at baseline in terms of age, gender, and frequency and intensity of symptoms, except for oedema, whose frequency and severity was significantly greater in the MPFF group (p = 0.024). During the 7-day treatment, there was a significant difference in favour of MPFF in the evolution of pain and oedema (p < or = 0.001 at D7) and in bleeding (p = 0.021 at D4, and p = 0.047 at D7). The appreciation of global efficacy by patients (p = 0.007) or investigators (p = 0.006) also favoured MPFF. Blood pressure, heart rate and laboratory parameters remained within normal ranges and were not modified during the study in either group. No patient had to stop the treatment owing to adverse events and only one patient reported gastrointestinal discomfort.
                MPFF significantly reduced the extent of pain and bleeding in the selected subjects of this study with acute haemorrhoids. The tolerability was similar in patients receiving MPFF to that in patients receiving a placebo during the 7-day duration of the treatment.MPFF can be considered an effective and well-tolerated agent in the treatment of acute episodes of haemorrhoids. Hemorrhoidal disease (HD) is a trophic disorder of the anal canal characterized by recurrent, self-resolving acute episodes. The author reports the results of a double-blind, placebo-controlled trial of the efficacy of Daflon 500 mg in the treatment of acute and chronic symptoms of hemorrhoids. One hundred and twenty outpatients (54 men, 66 women) suffering from an acute episode of HD during the previous two months were included. They received Daflon 500 mg (group D, n = 60) or placebo (group P, n = 60) two tablets daily for two months. The patients were examined at entry (T0) and at two months (T2). At T0, the two groups did not differ in terms of age, sex, weight, height, history of symptoms of HD; 7 patients were excluded from analysis because of treatment failure (group D, n = 2; group P, n = 3), or lost to follow-up (group P, n = 2). In group D, 40% of patients had an attack during the trial with a mean duration of 2.6 days and a mean severity of 1.1 scored on a scale from 1 to 3. These values were significantly different (P < 0.01) from the corresponding values in the P group: 70%, 4.6 days and 1.6 respectively. Each symptom and sign was scored on a scale of severity. The overall symptom score, scored from 0 to 15, decreased from 6.6 (group D) and 6.1 (group P) (NS) to 1.1 and 4.0 respectively (P < 0.01) at the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) Flavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination between troxerutin 150 mg and carbazochrome 1.5 mg (Fleboside ampoules) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids. The purpose of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients. 30 patients were randomized to receive one of two treatments: troxerutin 150 mg and carbazochrome 1.5 mg, or placebo, i.m. 3 ml ampoules twice a day for five consecutive days after the surgical procedure, starting from the day of surgery. Efficacy parameters were assessed as follows: at baseline (T1), after the first administration (T2; day of surgery), the second day after the surgical procedure (T3), and the fifth day after the surgical procedure (T4); hemorrhoidal symptoms based on a visual analogue scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; analgesic intake, if any; time to restore a physiological defecation; edema evaluation (based on a four-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe); camera pictures taken at T1 and T4 (in selected patients); and blood coagulation tests. Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score (p = 0.007 and p = 0.001, respectively) in favor of the active combination treatment. A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 (p < 0.001) in favor of the active combination group. No adverse events were reported. Neither the active combination nor placebo affected blood coagulation tests. We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and carbazochrome 1.5 mg is effective, well tolerated and superior to placebo in improving hemorrhoidal and post-surgical symptoms during the five days following surgery. The aim of this study was to evaluate if the combination of micronized purified flavonoid fraction with short-term routine antibiotic and anti-inflammatory therapy was better at reducing the intensity of postoperative symptoms and wound bleeding after a Milligan-Morgan's open hemorrhoidectomy than antibiotic and anti-inflammatory treatment alone.
                Fifty patients were randomly assigned to receive routine antibiotic and anti-inflammatory treatment alone (control patients) or a combination of micronized purified flavonoid fraction with identical antibiotic and anti-inflammatory treatment (micronized purified flavonoid fraction patients). The evolution of symptoms (pain, tenesmus, pruritus, and bleeding) during the postoperative period was assessed by means of patients' self-questionnaires. Each symptom was scored on a graded severity scale from 0 to 3, daily during the first three days of the immediate postoperative period, then at regular intervals (about every 14 days) until postoperative day 60. A global score for evaluation of each postoperative symptom and bleeding was used. The global score for each symptom was the sum of scores for each patient over the study period. The global score for each symptom was compared between the two groups with the Mann-Whitney U test.
                No significant differences in age, gender distribution, and stage of disease between the two groups were noticed at baseline. Posthemorrhoidectomy symptoms were relieved more rapidly in the micronized purified flavonoid fraction group; during the first three postoperative days, the global score for each symptom was significantly more reduced in the micronized purified flavonoid fraction group. The global scores for each symptom are as follows: pain after 3 days, 6.16 (SD = 1.9) in the control group vs. 3.48 (SD = 1.8) in the micronized purified flavonoid fraction group (P < 0.0001); tenesmus, 5.36 (SD = 1.8) in the control group vs. 1.48 (SD = 1.5) in the micronized purified flavonoid fraction group (P < 0.0001); pruritus, 4.04 (SD = 1.9) in the control group vs. 1.84 (SD = 1.4) in the micronized purified flavonoid fraction group (P < 0.0001); bleeding, 4.4 (SD = 2.1) in the control group vs. 2.0 (SD = 1.3) in the micronized purified flavonoid fraction group (P < 0.0001). A significant difference (P < 0.0001) between groups was also shown in favor of micronized purified flavonoid fraction patients when global scores were calculated over the entire study period (60 days).
                Micronized purified flavonoid fraction used in combination with short-term antibiotic and anti-inflammatory treatment can reduce both the duration and extent of postoperative symptoms and wound bleeding following hemorrhoidectomy. The pharmacological treatment is widely used in the therapy of haemorrhoids. An efficient treatment is particularly useful in case of haemorrhoids of 2nd, 3rd and 4th degree, when phlogosis, oedema and pain are present. Forty patients were treated with either O-(beta-hydroxyethyl)-rutosides (4 g/day orally) or placebo in a double blind randomized comparative trial. The groups of treatment were homogeneous. O-(beta-hydroxyethyl)-rutosides induced a statistically significant reduction of pain and bleeding; placebo did not induce any significant improvement. Tolerability was good and similar for both treatments. It has never been necessary to stop treatment for side effects. The results obtained in this study confirm the usefulness on administering an oral treatment, and not only a local treatment, to patients with acute symptoms of haemorrhoids, both in case of intermittent treatment and in case it is used to prepare quickly the patient for surgery. Infrared photocoagulation (IRP) is commonly used in the treatment of hemorrhoids, but rectal bleeding can persist after this procedure. Adjuvant therapy may thus be considered for more definitive control of symptoms, particularly bleeding.
                The goal of this study was to compare the efficacy of a treatment combining IRP and oral micronized purified flavonoid fraction (MPFF) versus each treatment used alone on bleeding cessation in patients with grades I, II, and III acute internal hemorrhoids.
                This was a prospective, randomized, controlled, single-blind study. Consecutive outpatients were randomly assigned to a treatment combining MPFF and IRP or to each treatment separately. For each patient, bleeding status was reported at day 0 (day of inclusion) and compared with that at day 5 after treatment by observers blinded to treatment assignment. Follow-up visits were planned at days 7, 30, 60, and 90 of therapy, including monitoring of treatment-related side effects and self-reporting by patients of any problem related to hemorrhoidal disease.
                A total of 351 patients (180 women, 171 men) were enrolled in the study. Their mean age was 49.2 years (range, 29-71 years). Hemorrhoids were grade I in 33.6% (118 patients), grade II in 48.7% (171 patients), and grade III in 17.7% (62 patients) of the study population. Patients were randomly assigned to each of the 3 treatment groups (117 patients in each), with no significant difference between groups in the age, sex, or distribution of grade of hemorrhoids. The percentage of patients with no bleeding after 5 days of treatment was higher in the combined treatment group (74.8%) compared with MPFF alone (59.6%; P = 0.023) or with IRP alone (55.6%; P = 0.004). MPFF alone was as effective as IRP alone at stopping bleeding. Patients with grades I and II hemorrhoids responded significantly better (82.5% and 61.7%, respectively) to either treatment than those with grade III hemorrhoids (22.9%; P < 0.001). Of the 216 patients who were followed up for 90 days, 3 had a gastrointestinal adverse event, and 19 had a relapse of bleeding.
                Five days of treatment combining MPFF with IRP significantly reduced bleeding status in these study patients with grades I and II acute internal hemorrhoids compared with each treatment used alone. To demonstrate the value of Diosmin (flavonidic fraction) in the management of post-haemorhoidectomic symptoms.
                Eighty-six consecutive patients with grades III and IV acute mixed hemorrhoids admitted to the Anorectal Surgical Department of First Affiliated Hospital, Xinjiang Medical University from April 2009 to April 2010, were enrolled in this study. An observer-blinded, randomized trial was conducted to compare post-haemorhoidectomic symptoms with use of Diosmin flavonidic fraction vs placebo. Eighty-six patients were randomly allocated to receive Diosmin flavonidic fraction 500 mg for 1 wk (n = 43) or placebo (n = 43). The Milligan-Morgan open haemorrhoidectomy was performed by a standardized diathermy excision method. Pain, bleeding, heaviness, pruritus, wound edema and mucosal discharge were observed after surgery. The postoperative symptoms and hospitalization time were recorded.
                The mean age of the Diosmin group and controls was 53.2 and 51.3 years, respectively. In Diosmin group, haemorrhoid piles were of the third degree in 33 patients and the fourth degree in 10; and in the control group, 29 were of the third degree and 14 were of the fourth degree. There was no statistically significance in age, gender distribution, degree and number of excised haemorrhoid piles, and the mean duration of haemorrhoidal disease between the two groups. There was a statistically significant improvement in pain, heaviness, bleeding, pruritus from baseline to the 8th week after operation (P < 0.05). Patients taking Diosmin had a shorter hospitalization stay after surgery (P < 0.05). There was also a significant improvement on the proctoscopic appearance (P < 0.001). However, there was no statistical difference between the two groups in terms of wound mucosal discharge. Two patients experienced minor bleeding at the 8th week in Diosmin group, and underwent surgery.
                Diosmin is effective in alleviating postoperational symptoms of haemorrhoids. Therefore, it should be considered for the initial treatment after haemorrhoid surgery. However, further prospective randomized trials are needed to confirm the findings of this study. This multicenter, double-blind, randomised study was undertaken to determine the efficacy and safety of a combination of troxerutin 150 mg and carbazochrome 1.5 mg compared to carbazochrome alone in patients with acute uncomplicated hemorrhoids. Patients were administered by the intramuscular route (one ampoule) twice daily for one week. Both subjective and objective efficacy variables significantly improved in the combination drug group only, thus demonstrating the rationale for a combination therapy. Treatments were safe and well tolerated either at a local or systemic level. Patients with acute bleeding from internal haemorrhoids often have to be referred by the general practitioner to the surgeon for definitive treatment with invasive outpatient procedures. At the initial consultation, patients frequently seek postponement of immediate surgery to a more convenient time. Effective and rapid non-invasive control of acute bleeding could be of practical use in scheduling surgery to a time convenient to both patient and surgeon.
                In a 90-day randomized, double-blind study treatment with a micronized purified flavonoid fraction (MPFF) was compared with placebo, in 100 outpatients who presented for treatment of acute internal haemorrhoids of less than 3 days' duration. The primary endpoint was cessation of bleeding on the third day of treatment.
                Of 50 patients randomized to each group, acute bleeding ceased by the third day in 40 (80 per cent) who received MPFF compared with 19 (38 per cent) who had placebo (P < 0.01). Mean(s.d. ) duration of acute bleeding from onset to cessation of 4.9(1.6) days was 2.1 (95 per cent confidence interval 1.2-2.9) days less than that in patients receiving placebo (P < 0.01). Continued treatment in patients with no bleeding prevented a relapse in 30 of 47 patients, compared with 12 of 30 receiving placebo (P < 0.05).
                Patients with acute internal haemorrhoids treated with MPFF had rapid cessation of bleeding and a reduced risk of relapse. This could be of value in the more convenient timing of treatment with invasive outpatient procedures. We investigated the efficacy of orally and topically applied Pycnogenol for the management of acute hemorrhoidal attacks in a controlled, randomized study with 84 subjects. Within less than 48 h of onset of an acute attack, patients were enrolled and signs and symptoms were scored. This evaluation was repeated after seven days' treatment and again seven days following treatment cessation. The decrease in scores was significantly more pronounced in the Pycnogenol-treated groups than in the control group given placebo (p < 0.05), showing the efficacy of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In a group of patients given topical (0.5%) Pycnogenol in addition to oral Pycnogenol the improvement in symptoms set in significantly faster and was more pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely absent in all patients treated with Pycnogenol for seven days and also at the 14 days follow-up. In contrast, bleedings were still observed in the control group during the two weeks follow-up. This study indicates that Pycnogenol, both in oral and in topical form, is effective for controlling this common, disabling health problem. The application of Pycnogenol eases the management of acute hemorrhoidal attacks and help avoid bleedings.
                (c) 2009 John Wiley & Sons, Ltd. A prospective randomized controlled trial was carried out on the effects of Daflon 500 mg (a micronized flavonidic fraction containing diosmin 450 mg and hesperidin 50 mg) on bleeding after haemorrhoidectomy. In all, 228 consecutive patients with prolapsed irreducible piles were recruited. Elective haemorrhoidectomy was performed with a standardized diathermy excision method. Some 114 patients were randomized to receive Daflon 500 mg for 1 week after operation (group 1), and there were 114 controls (group 2). Postoperative analgesia and laxative prescription as well as hospital stay were otherwise the same. One patient (0.9 per cent) from group 1 and seven (6.1 per cent) from group 2 had postoperative bleeding (P = 0.03). All bleeding occurred from 6 to 15 days after haemorrhoidectomy. There were no side-effects from the use of Daflon 500 mg. The risk of secondary bleeding from haemorrhoidectomy is reduced with postoperative Daflon. We conducted a prospective randomized controlled study to evaluate the effect of micronized flavonoid fractions (MFF) on pain after hemorrhoidectomy.
                The subjects were 112 consecutive patients randomly assigned either to receive MFF (group 1) for 1 week or not to receive MFF, as a control (group 2), after hemorrhoidectomy, The severity of pain and the number of intramuscular analgesic injections required were recorded for the first 3 days, then 1 week after hemorrhoidectomy. The number of days that intramuscular analgesic injections were required, hospital stay, and patient satisfaction were also assessed.
                On postoperative day (POD) 1, there were no significant differences between the parameters of the two groups, but on PODs 2 and 3, both the pain score ( P = 0.033 and P = 0.011, respectively) and the number of patients who required intramuscular analgesic injections were significantly less in group 1 ( P = 0.022 and P = 0.007, respectively). Moreover, the hospital stay was shorter and patient satisfaction was superior in group 1 ( P = 0.001 and P = 0.001, respectively). After 1 week, the pain score and number of intramuscular analgesic injections given were significantly less in group 1 ( P = 0.001 and P = 0.021).
                Using MFF after hemorrhoidectomy reduced the severity of pain and intramuscular analgesic requirement. A randomized, double-blind, controlled study was conducted to investigate the efficacy of oral calcium dobesilate therapy in treating acute attacks of internal hemorrhoids.
                Twenty-nine well-documented adult patients with first- or second-degree internal hemorrhoids were treated with calcium dobesilate for two weeks, while16 patients received only a high-fiber diet to serve as control. Both symptoms and anoscopic inflammation were scored on a scale from 0 to 2 before (T0) and two weeks after treatment (T2).
                A success rate of 86.21 percent with cessation of bleeding plus lack of severe anitis anoscopically at two weeks were achieved with calcium dobesilate. The pretreatment symptom score of 2 fell significantly to 0.45 +/- 0.13, and the pretreatment anitis score of 1.69 +/- 0.09 fell to 0.55 +/- 0.12 at T2 (P = 0.0001 for both comparisons). The symptom and anoscopic inflammation scores obtained with calcium dobesilate treatment were also significantly better than those with diet only (P = 0.0017 and P = 0.0013, respectively).
                Together with recommendations about diet and bowel discipline, oral calcium dobesilate treatment provides an efficient, fast, and safe symptomatic relief from acute symptoms of hemorrhoidal disease. This symptomatic healing is associated with a significant improvement in the anoscopically observed inflammation. Control of postoperative symptoms is of paramount importance in ambulatory surgery. This trial was conducted to evaluate whether a micronized purified flavonoid fraction (MPFF) (Detralex((R))) reduces postoperative bleeding, pain and consumption of analgesics after ambulatory stapled hemorrhoidopexy, as reported in trials after classic hemorrhoidectomy. Phlebotropic activity, protective effect on the capillaries and anti-inflammatory properties of this drug have been reported in several studies.
                Sixty-three patients with third-degree hemorrhoids had ambulatory stapled hemorrhoidopexy under spinal anesthesia in the period of one year. The patients were randomized, with 30 receiving Detralex 500 mg (2 tablets 3 times daily for 5 days after the operation) and 33 forming the control group. The patients were asked to daily self-assess the presence of blood on defecation, degree of pain and consumption of analgesics for the first week after the operation.
                There was no significant difference between the two groups in duration of presence of blood, degree of pain or analgesics requirement. No major complications, such as bleeding requiring transfusion or hospitalization, sepsis, anal stenosis or urgent defecation, were noted in the follow-up period. There were no side effects from Detralex treatment.
                In our study we could not demonstrate any positive effect of prescribing flavonoids after stapler hemorrhoidopexy. This procedure may not be sufficiently aggressive and is associated with too few postoperative complications to show any protective influence of flavonoids.
The evidence suggests that there is a potential benefit in using phlebotonics in treating haemorrhoidal disease as well as a benefit in alleviating post-haemorrhoidectomy symptoms. Outcomes such as bleeding and overall symptom improvement show a statistically significant beneficial effect and there were few concerns regarding their overall safety from the evidence presented in the clinical trials.
However methodological limitations were encountered. In order to enhance our conclusion further, more robust clinical trials which take into account these limitations will need to be performed in the future.